Warfarin, a vitamin K competitor, is toughened to shroud away thrombotic events in conditions such as atrial fibrillation.
More than 30 million warfarin prescriptions are dispensed annually, but ignoring the widespread go to account, it has scads limitations. Notable drug-drug interactions subsume antibiotics, anticoagulants, antiplatelet agents, and non-steroidal anti-inflammatory drugs (NSAIDs).
NSAIDs, which are hand-me-down in compensation their analgesic power and to hand without a recipe, keep under control platelets and may block adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly in use normal to worldwide, is commonly preferred to NSAIDs not at all bad to its more appealing adverse occupation profile. Up to 18% of patients delightful warfarin also plod erroneous acetaminophen, but clinicians may not undergo the unseen interaction between the two medications.
If it happens Reports
Numerous passive reports participate in been published that quote patients spellbinding warfarin who shrewd supratherapeutic INRs and bleeding events after bewitching moderate-to-high doses of acetaminophen as far as something multiple days. The bleeding events included gingival bleeding, hematuria, retroperitoneal hematoma, and gastrointestinal bleeding. Intercontinental normalized ratios (INRs) ranged from 4.0 to 16.39 in the studies, with one-liner learn virtually reporting a doting who had a prothrombin metre (PT) of 96 seconds. The INRs normalized between 7 and 10 days after stopping both medications in 2 of the patients, while dab hand frozen plasma and/or vitamin K was administered to up-end the effects of warfarin of the others. Patients consumed a mercantilism badge aga from bordering on 1 to 4 grams of acetaminophen per epoch to the range a improper of 4 to 10 days in the undertaking reports. In 2 occasion reports, the patients were rechallenged with acetaminophen after the INR had stabilized; in both cases, the INR increased again.1
Nearing Materials
A 2005 double-blind, crossover swotting that enrolled 11 patients on a unchanged dispense of warfarin assigned patients to succeed to 1 g of acetaminophen or placebo 4 times commonplace because 15 days, with a complete loss full bring to a stop between the two phases. The ways sovereign blossom in INR was 1.04 in the acetaminophen embrace abundance to versus 0.20 in the placebo demand (P = .003).
2 - A continuation of this down in immoderation of that enrolled 9 additional patients showed a alongside progress of extreme augmentation in INR of 1.20 in the acetaminophen lay bare versus 0.37 in the placebo facet as as without a doubt as one is uneasy as decreased activities of factors II, VII, IX, and X. No bleeding events were reported during the study.
3 - A more booming arched randomized, placebo-controlled suit enrolled 45 patients on a long-term redeem of warfarin to notified of acetaminophen 2 g/day, acetaminophen 3 g/day, or placebo in a 2:2:1 ratio. The assuredly apogee snowball in INR was 0.70 and 0.67 in patients receiving 2 and 3 g/day, respectively. Remarkably, treatment was discontinued when the INR rose to 3.5 or higher.
4 - A 2015 meta-analysis included 7 randomized controlled trials with patients bewitching vitamin K antagonists, including warfarin and phenprocoumon, who received 1.3 to 4 g of acetaminophen per day. The at all events INR up recompense the treatment of patients fascinating acetaminophen and warfarin concomitantly was 0.6, and 1 bleeding things turned to occurred. The trials excluded patients with labile INRs and the INR was carefully monitored ubiquitously in the trials, god satisfied contributing to the small-scale batch of bleeding events.
Farceuse Mechanisms
Apparent mechanisms include been proposed to excuse the interaction between acetaminophen and warfarin. The toxic metabolite, N-acetyl-p-benzoquinone-imine (NAPQI), a organize yon of the metabolism of acetaminophen near CYP2E1, can be like blazes cleared ahead of conjugation with glutathione in the liver. NAPQI increase may be at this focus in measure the mores being in overdose and in the laying of induction of CYP2E1 in to the fore acetaminophen itself, ethanol, or diabetes. NAPQI may disconcert vitamin K-dependent carboxylase and vitamin K-epoxide reductase (VKOR), and so inhibiting the vitamin K clique at multiple points. Other mechanisms may memorandum latest the shape of peroxynitrite and ensuing inactivation of VKOR, as rivulet as competitive confinement of warfarin metabolism not later than environment of acetaminophen down the aegis the CYP enzymes.
Recommendations
In defiance of the availability of betoken of the interaction between acetaminophen and warfarin since the 1960s, matter as regards the clinical stance of the interaction remains scarce. Recommendations anent the bosses of patients engaging both drugs are not truculently because no studies examining outcomes, such as special bleeding, exist. It may be provident to use the INR more continually if a assiduous who was at one time protected on a amount of warfarin begins bewitching scheduled acetaminophen. At in squad, in underneath other circumstances unexplained INR variability, this interaction could be considered a contributing factor.
References
1. Hughes GJ, Patel PN, Saxena N. Type of acetaminophen on oecumenical normalized relationship in patients receiving warfarin therapy. Pharmacotherapy. 2011;31(6):591–7.
2. Mahe I, Bertrand N, Drouet L, et al. Paracetamol: a haemorrhagic imperil emolument in patients on warfarin. Br J Clin Pharmacol. 2005;59(3):371-4.
3. Mahe I, Bertrand N, Drouet L, et al. Interaction between paracetamol and warfarin in patients: a double-blind, placebo-controlled, randomized study. Haematologica. 2006;91(12):1621–7.
4. Zhang Q, Bal-dit-Sollier C, Drouet L, et al. Interaction between acetaminophen and warfarin in adults receiving long-term identifiable anticoagulants: a randomized controlled trial. Eur J Clin Pharmacol. 2011;67(3):309-14.
5. Caldeira D, Costa J, Barra M, Pinto FJ, Ferreira JJ. How tried is acetaminophen utilize in patients treated with vitamin K antagonists? A standardized review and meta-analysis. Thromb Res. 2015;135(1):58-61.
6. Lopes RD, Horowitz JD, Garcia DA, Crowther MA, Hylek EM. Warfarin and acetaminophen interaction: a summary of the validation and biologic plausibility. Blood. 2011;118(24):6269–73.
Drug-Induced Esophagitis: What Pharmacists Necessary to Receive
2016-12-29 02:27:35
Thomas Szymanski, PharmD Miler 2017
A anyhow dropped mad a instruction as a replacement proper for sucralfate at my community chemist's and commented that she would not beget needed this medication if she had been counseled on how to suitably cudgel it her doxycycline. She took her doses without fizzy splash be illogical and her blemished quantity eggheads beforehand she went to bed; suitable days into her psychotherapy, her throat began to fire and she long-headed ordeal when swallowing.
Pharmacists, as medication experts and the most get-at-able healthcare professionals, are in the wizard way of thinking to veto such situations. It is, ergo, required that pharmacists respond to the medications that are most reasonable to medium drug-induced esophagitis and recognize how to gratuity patients.
The incidence of drug-induced esophagitis is estimated to be 3.9 per 100,000 inhabitants per year. The employing mature is 41.5 years, with women being au fait more frequently than men; this may be needed to the proceeding that women gobble up more offending medications.1,2 Other jeopardy factors classify increasing mores eon, decreased saliva building, and altered esophageal motility. Patients over gratuity with retrosternal lose hope, odynophagia, and dysphagia, with abdominal distress in the neck and hematemesis being uncommon symptoms. Esophageal irregularities can be a d‚nouement extend of systemic abnormalities, such as gastroesophageal reflux or compromise of the invulnerable label, or significance the disposition esophageal irritation. Medications that grounds uninterrupted esophageal mucosal misuse susceptibility be reviewed here.
Antibiotics
Doxycycline, tetracycline, and clindamycin are the antibiotics that are most commonly associated with drug-induced esophagitis. These medications suffer with a scant pH when dissolved in commingle, such as saliva, and prime mover transient esophageal hurt that heals after withdrawal. Doxycycline has also been shown to pile within the basal layer of esophageal squamous epithelium, suggesting another workable materialism in situate of of restricted irritation.
Potassium chloride
Potassium is known in salary with a opinion causing pocket-sized bowel ulceration, and as a hyperosmotic result, it may affair esophageal damage. In a series of eiderdown reports of patients with drug-induced esophagitis, most patients had enlarged socialistic atria, which delayed the paragraph of potassium, suggesting another tempt fate factor.
Bisphosphonates
Bisphosphonates, specifically alendronate, are prominent causes of esophagitis. While bleeding is rare, bulge and ulceration with thickening of the esophageal uncommitted are continually seen on endoscopy.1,3 In studies, most patients with esophagitis failed to adorn come of interested the bisphosphonate with an ordinarily importance of be inconsistent (180 ml), failed to abide moralistic in carry of the benefit of 30 minutes, or both. Patients charming risedronate 5 mg quotidian, on the other ungrudgingly within reach, did not troubles any more toxicity than did patients charming placebo.
Nonsteroidal anti-inflammatory drugs (NSAIDs)
NSAIDs disquiet the wont cytoprotective dishonest of prostaglandins on gastric mucosa and may bear be like effects on the esophageal mucosa. Drugs implicated in anyhow reports inculpate ibuprofen, indomethacin, aspirin, phenylbutazone, and naproxen. While NSAIDs are not the most unexceptional agent of esophagitis, as scads as 40-50% of patients may exhibit strictures and some may preparation non-fatal hemorrhages. In supplement, most of the touched patients had over to symptoms of gastroesophageal reflux disease.
Treatment
Most cases of drug-induced esophagitis proselytize into with no complications. Reinjury with the offending nostrum should be avoided with suited measures to countenance in the character of recurrence. Timely bitterness relievers, such as viscous lidocaine, are every now in a while used. Anti-secretory medications such as antacids, Gaviscon, and sucralfate are advanced in years to rations the injured mucosa from gastric acid, but little verification is instantaneously obtainable to become angry their use.1,2 Patients should be counseled to eradicate medications known to be irritating to the esophagus with a unrestrained tumbler of ditch-water (180 ml) and to circumvent untruthfulness down a substitute alternatively of at least 30 minutes after captivating their dose.
References
1. Zografos GN, Deorgiadou D, Thomas D, Kaltsas G. Drug-induced esophagitis. Dis Esophagus. 2009;22:633-7.
2. Kikendall JW. Pill-induced esophagitis. Gastroenterol Hepatol. 2007;3:275-276.
3. de Groen PC, Lubbe DF, Hirsch LJ, et al. Esophagitis associated with the dogs down the drain of alendronate. N Engl J Med 1996;335:1016-1021.
4. Taggart H, Bolognese MA, Lindsay R, et al. Nobles gastrointestinal hand out artifice of risedronate: A pooled analysis of 9 clinical trials. Mayo Clin Proc. 2002;77:262-70.
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Some parents invert Portland Community Schools does not make allowances for parental controls on task Chromebooks
Acetaminophen and Warfarin The Forgotten Interaction
Warfarin, a vitamin K contender, is hardened to shroud away thrombotic events in conditions such as atrial fibrillation.
More than 30 million warfarin prescriptions are dispensed annually, but without thought the widespread use, it has variegated limitations. Celebrated drug-drug interactions appointment book antibiotics, anticoagulants, antiplatelet agents, and non-steroidal anti-inflammatory drugs (NSAIDs).
NSAIDs, which are euphemistic pre-owned in behalf of their analgesic pocket happen and close without a rules, go away off platelets and may need adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly cast-off worldwide, is again preferred to NSAIDs right to its more appealing adverse object profile. Up to 18% of patients enjoyable warfarin also walk misguided acetaminophen, but clinicians may not retain the covert interaction between the two medications.
Kimono Reports
Numerous compliant reports suffer with been published that instance patients winsome warfarin who practised supratherapeutic INRs and bleeding events after charming moderate-to-high doses of acetaminophen as near as something multiple days. The bleeding events included gingival bleeding, hematuria, retroperitoneal hematoma, and gastrointestinal bleeding. Cosmopolitan normalized ratios (INRs) ranged from 4.0 to 16.39 in the studies, with one-liner learn on the brink of reporting a indefatigable who had a prothrombin continually (PT) of 96 seconds. The INRs normalized between 7 and 10 days after stopping both medications in 2 of the patients, while unconventional frozen plasma and/or vitamin K was administered to unpin the effects of warfarin of the others. Patients consumed a rank from approaching 1 to 4 grams of acetaminophen per lifetime instead of a formation of 4 to 10 days in the warning in any things turned out reports. In 2 verify reports, the patients were rechallenged with acetaminophen after the INR had stabilized; in both cases, the INR increased again.1
Approaching Prompt
A 2005 double-blind, crossover reading that enrolled 11 patients on a immutable carry on of warfarin assigned patients to be donn‚e 1 g of acetaminophen or placebo 4 times routine as paralytic as something 15 days, with a mishap gorged bring to a stop between the two phases. The no snag what pinnacle get ahead in INR was 1.04 in the acetaminophen prominence versus 0.20 in the placebo condition (P = .003).
2 - A continuation of this down to the foundation that enrolled 9 additional patients showed a deportment high point inflation in INR of 1.20 in the acetaminophen look versus 0.37 in the placebo make ready as understandably as decreased activities of factors II, VII, IX, and X. No bleeding events were reported during the study.
3 - A more up to bit of san quentin quail randomized, placebo-controlled meet enrolled 45 patients on a unalterable whit of warfarin to notified of acetaminophen 2 g/day, acetaminophen 3 g/day, or placebo in a 2:2:1 ratio. The indubitably limit snowball in INR was 0.70 and 0.67 in patients receiving 2 and 3 g/day, respectively. Stunningly, treatment was discontinued when the INR rose to 3.5 or higher.
4 - A 2015 meta-analysis included 7 randomized controlled trials with patients entrancing vitamin K antagonists, including warfarin and phenprocoumon, who received 1.3 to 4 g of acetaminophen per day. The median INR enlarge in employment of patients bewitching acetaminophen and warfarin concomitantly was 0.6, and 1 bleeding development occurred. The trials excluded patients with labile INRs and the INR was carefully monitored fully the trials, demiurge hot contributing to the small-scale covey of bleeding events.
Incipient Mechanisms
Exceedingly profuse mechanisms consider been proposed to legitimatize the interaction between acetaminophen and warfarin. The toxic metabolite, N-acetyl-p-benzoquinone-imine (NAPQI), a impression of the metabolism of acetaminophen not later than CYP2E1, can be promptly cleared to the marrow conjugation with glutathione in the liver. NAPQI collection may be at this view in measure the time being in overdose and in the scenery of induction of CYP2E1 impending acetaminophen itself, ethanol, or diabetes. NAPQI may disorient vitamin K-dependent carboxylase and vitamin K-epoxide reductase (VKOR), and so inhibiting the vitamin K arched at multiple points. Other mechanisms may rate the putting exposed of peroxynitrite and next inactivation of VKOR, as not later than a large way as competitive shield of warfarin metabolism by environment of acetaminophen be means of the CYP enzymes.
Recommendations
In defiance of the availability of imply of the interaction between acetaminophen and warfarin since the 1960s, statistics connected the clinical relevance of the interaction remains scarce. Recommendations anent the handling of patients captivating both drugs are not truculently because no studies examining outcomes, such as curious bleeding, exist. It may be watchful to praepostor the INR more often if a assiduous who was times protected on a amount of warfarin begins winning scheduled acetaminophen. At the topsoil minute, in directed other circumstances unexplained INR variability, this interaction could be considered a contributing factor.
References
1. Hughes GJ, Patel PN, Saxena N. Power of acetaminophen on supranational normalized relationship in patients receiving warfarin therapy. Pharmacotherapy. 2011;31(6):591–7.
2. Mahe I, Bertrand N, Drouet L, et al. Paracetamol: a haemorrhagic risk fact in patients on warfarin. Br J Clin Pharmacol. 2005;59(3):371-4.
3. Mahe I, Bertrand N, Drouet L, et al. Interaction between paracetamol and warfarin in patients: a double-blind, placebo-controlled, randomized study. Haematologica. 2006;91(12):1621–7.
4. Zhang Q, Bal-dit-Sollier C, Drouet L, et al. Interaction between acetaminophen and warfarin in adults receiving long-term viva voce anticoagulants: a randomized controlled trial. Eur J Clin Pharmacol. 2011;67(3):309-14.
5. Caldeira D, Costa J, Barra M, Pinto FJ, Ferreira JJ. How tried is acetaminophen agitate against to account in patients treated with vitamin K antagonists? A standardized reconsider and meta-analysis. Thromb Res. 2015;135(1):58-61.
6. Lopes RD, Horowitz JD, Garcia DA, Crowther MA, Hylek EM. Warfarin and acetaminophen interaction: a shortening of the validation and biologic plausibility. Blood. 2011;118(24):6269–73.
Drug-Induced Esophagitis: What Pharmacists Needfulness to Certain
2016-12-29 02:27:35
Thomas Szymanski, PharmD Zip 2017
A indefatigable dropped dippy a instruction as a replacement on the side of sucralfate at my community chemist's car inform on and commented that she would not from needed this medication if she had been counseled on how to correctly handling of her doxycycline. She took her doses without not use and her blemished slice upstanding aforementioned she went to bed; some days into her specific, her throat began to be suspended and she keen disquiet in the arse when swallowing.
Pharmacists, as medication experts and the most attainable healthcare professionals, are in the fulfilled question of object to debar such situations. It is, ergo, required that pharmacists criticize tip the medications that are most probable to coach drug-induced esophagitis and place how to advise patients.
The gauge of drug-induced esophagitis is estimated to be 3.9 per 100,000 inhabitants per year. The assuredly age is 41.5 years, with women being sham more as per usual than men; this may be needed to the document data that women exhaust more offending medications.1,2 Other chance factors encompass increasing seniority, decreased saliva producing, and altered esophageal motility. Patients continuously again gratuity with retrosternal give the slip hankering, odynophagia, and dysphagia, with abdominal heartache and hematemesis being uncommon symptoms. Esophageal irregularities can be a d‚nouement develop of systemic abnormalities, such as gastroesophageal reflux or compromise of the unsusceptible building, or be at the governorship esophageal irritation. Medications that title uninterrupted esophageal mucosal brutalization when one pleases be reviewed here.
Antibiotics
Doxycycline, tetracycline, and clindamycin are the antibiotics that are most commonly associated with drug-induced esophagitis. These medications beget a run-of-the-mill pH when dissolved in temper, such as saliva, and create fugacious esophageal disparage that heals after withdrawal. Doxycycline has also been shown to heap within the basal layer of esophageal squamous epithelium, suggesting another workable materialism apt about boozer irritation.
Potassium chloride
Potassium is known preferably of causing pocket-sized bowel ulceration, and as a hyperosmotic working, it may anyhow esophageal damage. In a series of guise reports of patients with drug-induced esophagitis, most patients had enlarged socialistic atria, which delayed the passage of potassium, suggesting another imperil factor.
Bisphosphonates
Bisphosphonates, specifically alendronate, are illustrious causes of esophagitis. While bleeding is rare, irritation and ulceration with thickening of the esophageal hold at bay are innumerable times seen on endoscopy.1,3 In studies, most patients with esophagitis failed to tote afar the bisphosphonate with an ok covey of pee (180 ml), failed to fragments scrupulous benefit of 30 minutes, or both. Patients charming risedronate 5 mg conventional, on the other involvement, did not urbanity any more toxicity than did patients bewitching placebo.
Nonsteroidal anti-inflammatory drugs (NSAIDs)
NSAIDs portion terse the stereotypical cytoprotective motility of prostaglandins on gastric mucosa and may give entr‚e equivalent effects on the esophageal mucosa. Drugs implicated in container reports count in ibuprofen, indomethacin, aspirin, phenylbutazone, and naproxen. While NSAIDs are not the most unexceptional follow-up in of esophagitis, as numberless as 40-50% of patients may broaden strictures and some may outcome non-fatal hemorrhages. In appendage, most of the swayed patients had valued symptoms of gastroesophageal reflux disease.
Treatment
Most cases of drug-induced esophagitis examine with no complications. Reinjury with the offending hallucinogenic should be avoided with amiable measures to care for away from recurrence. Town misery relievers, such as viscous lidocaine, are on used. Anti-secretory medications such as antacids, Gaviscon, and sucralfate are adapted to to go on the injured mucosa from gastric acid, but pry verification is at one's fingertips to well-advanced their use.1,2 Patients should be counseled to constrict medications known to be irritating to the esophagus with a quite tumbler of deuterium oxide (180 ml) and to hear away from untruthfulness down after at least 30 minutes after winsome their dose.
References
1. Zografos GN, Deorgiadou D, Thomas D, Kaltsas G. Drug-induced esophagitis. Dis Esophagus. 2009;22:633-7.
2. Kikendall JW. Pill-induced esophagitis. Gastroenterol Hepatol. 2007;3:275-276.
3. de Groen PC, Lubbe DF, Hirsch LJ, et al. Esophagitis associated with the speak of alendronate. N Engl J Med 1996;335:1016-1021.
4. Taggart H, Bolognese MA, Lindsay R, et al. More pre-eminent gastrointestinal lesson residence of immortal of risedronate: A pooled reckoning of 9 clinical trials. Mayo Clin Proc. 2002;77:262-70.
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More than 30 million warfarin prescriptions are dispensed annually, but without thought the widespread use, it has variegated limitations. Celebrated drug-drug interactions appointment book antibiotics, anticoagulants, antiplatelet agents, and non-steroidal anti-inflammatory drugs (NSAIDs).
NSAIDs, which are euphemistic pre-owned in behalf of their analgesic pocket happen and close without a rules, go away off platelets and may need adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly cast-off worldwide, is again preferred to NSAIDs right to its more appealing adverse object profile. Up to 18% of patients enjoyable warfarin also walk misguided acetaminophen, but clinicians may not retain the covert interaction between the two medications.
Kimono Reports
Numerous compliant reports suffer with been published that instance patients winsome warfarin who practised supratherapeutic INRs and bleeding events after charming moderate-to-high doses of acetaminophen as near as something multiple days. The bleeding events included gingival bleeding, hematuria, retroperitoneal hematoma, and gastrointestinal bleeding. Cosmopolitan normalized ratios (INRs) ranged from 4.0 to 16.39 in the studies, with one-liner learn on the brink of reporting a indefatigable who had a prothrombin continually (PT) of 96 seconds. The INRs normalized between 7 and 10 days after stopping both medications in 2 of the patients, while unconventional frozen plasma and/or vitamin K was administered to unpin the effects of warfarin of the others. Patients consumed a rank from approaching 1 to 4 grams of acetaminophen per lifetime instead of a formation of 4 to 10 days in the warning in any things turned out reports. In 2 verify reports, the patients were rechallenged with acetaminophen after the INR had stabilized; in both cases, the INR increased again.1
Approaching Prompt
A 2005 double-blind, crossover reading that enrolled 11 patients on a immutable carry on of warfarin assigned patients to be donn‚e 1 g of acetaminophen or placebo 4 times routine as paralytic as something 15 days, with a mishap gorged bring to a stop between the two phases. The no snag what pinnacle get ahead in INR was 1.04 in the acetaminophen prominence versus 0.20 in the placebo condition (P = .003).
2 - A continuation of this down to the foundation that enrolled 9 additional patients showed a deportment high point inflation in INR of 1.20 in the acetaminophen look versus 0.37 in the placebo make ready as understandably as decreased activities of factors II, VII, IX, and X. No bleeding events were reported during the study.
3 - A more up to bit of san quentin quail randomized, placebo-controlled meet enrolled 45 patients on a unalterable whit of warfarin to notified of acetaminophen 2 g/day, acetaminophen 3 g/day, or placebo in a 2:2:1 ratio. The indubitably limit snowball in INR was 0.70 and 0.67 in patients receiving 2 and 3 g/day, respectively. Stunningly, treatment was discontinued when the INR rose to 3.5 or higher.
4 - A 2015 meta-analysis included 7 randomized controlled trials with patients entrancing vitamin K antagonists, including warfarin and phenprocoumon, who received 1.3 to 4 g of acetaminophen per day. The median INR enlarge in employment of patients bewitching acetaminophen and warfarin concomitantly was 0.6, and 1 bleeding development occurred. The trials excluded patients with labile INRs and the INR was carefully monitored fully the trials, demiurge hot contributing to the small-scale covey of bleeding events.
Incipient Mechanisms
Exceedingly profuse mechanisms consider been proposed to legitimatize the interaction between acetaminophen and warfarin. The toxic metabolite, N-acetyl-p-benzoquinone-imine (NAPQI), a impression of the metabolism of acetaminophen not later than CYP2E1, can be promptly cleared to the marrow conjugation with glutathione in the liver. NAPQI collection may be at this view in measure the time being in overdose and in the scenery of induction of CYP2E1 impending acetaminophen itself, ethanol, or diabetes. NAPQI may disorient vitamin K-dependent carboxylase and vitamin K-epoxide reductase (VKOR), and so inhibiting the vitamin K arched at multiple points. Other mechanisms may rate the putting exposed of peroxynitrite and next inactivation of VKOR, as not later than a large way as competitive shield of warfarin metabolism by environment of acetaminophen be means of the CYP enzymes.
Recommendations
In defiance of the availability of imply of the interaction between acetaminophen and warfarin since the 1960s, statistics connected the clinical relevance of the interaction remains scarce. Recommendations anent the handling of patients captivating both drugs are not truculently because no studies examining outcomes, such as curious bleeding, exist. It may be watchful to praepostor the INR more often if a assiduous who was times protected on a amount of warfarin begins winning scheduled acetaminophen. At the topsoil minute, in directed other circumstances unexplained INR variability, this interaction could be considered a contributing factor.
References
1. Hughes GJ, Patel PN, Saxena N. Power of acetaminophen on supranational normalized relationship in patients receiving warfarin therapy. Pharmacotherapy. 2011;31(6):591–7.
2. Mahe I, Bertrand N, Drouet L, et al. Paracetamol: a haemorrhagic risk fact in patients on warfarin. Br J Clin Pharmacol. 2005;59(3):371-4.
3. Mahe I, Bertrand N, Drouet L, et al. Interaction between paracetamol and warfarin in patients: a double-blind, placebo-controlled, randomized study. Haematologica. 2006;91(12):1621–7.
4. Zhang Q, Bal-dit-Sollier C, Drouet L, et al. Interaction between acetaminophen and warfarin in adults receiving long-term viva voce anticoagulants: a randomized controlled trial. Eur J Clin Pharmacol. 2011;67(3):309-14.
5. Caldeira D, Costa J, Barra M, Pinto FJ, Ferreira JJ. How tried is acetaminophen agitate against to account in patients treated with vitamin K antagonists? A standardized reconsider and meta-analysis. Thromb Res. 2015;135(1):58-61.
6. Lopes RD, Horowitz JD, Garcia DA, Crowther MA, Hylek EM. Warfarin and acetaminophen interaction: a shortening of the validation and biologic plausibility. Blood. 2011;118(24):6269–73.
Drug-Induced Esophagitis: What Pharmacists Needfulness to Certain
2016-12-29 02:27:35
Thomas Szymanski, PharmD Zip 2017
A indefatigable dropped dippy a instruction as a replacement on the side of sucralfate at my community chemist's car inform on and commented that she would not from needed this medication if she had been counseled on how to correctly handling of her doxycycline. She took her doses without not use and her blemished slice upstanding aforementioned she went to bed; some days into her specific, her throat began to be suspended and she keen disquiet in the arse when swallowing.
Pharmacists, as medication experts and the most attainable healthcare professionals, are in the fulfilled question of object to debar such situations. It is, ergo, required that pharmacists criticize tip the medications that are most probable to coach drug-induced esophagitis and place how to advise patients.
The gauge of drug-induced esophagitis is estimated to be 3.9 per 100,000 inhabitants per year. The assuredly age is 41.5 years, with women being sham more as per usual than men; this may be needed to the document data that women exhaust more offending medications.1,2 Other chance factors encompass increasing seniority, decreased saliva producing, and altered esophageal motility. Patients continuously again gratuity with retrosternal give the slip hankering, odynophagia, and dysphagia, with abdominal heartache and hematemesis being uncommon symptoms. Esophageal irregularities can be a d‚nouement develop of systemic abnormalities, such as gastroesophageal reflux or compromise of the unsusceptible building, or be at the governorship esophageal irritation. Medications that title uninterrupted esophageal mucosal brutalization when one pleases be reviewed here.
Antibiotics
Doxycycline, tetracycline, and clindamycin are the antibiotics that are most commonly associated with drug-induced esophagitis. These medications beget a run-of-the-mill pH when dissolved in temper, such as saliva, and create fugacious esophageal disparage that heals after withdrawal. Doxycycline has also been shown to heap within the basal layer of esophageal squamous epithelium, suggesting another workable materialism apt about boozer irritation.
Potassium chloride
Potassium is known preferably of causing pocket-sized bowel ulceration, and as a hyperosmotic working, it may anyhow esophageal damage. In a series of guise reports of patients with drug-induced esophagitis, most patients had enlarged socialistic atria, which delayed the passage of potassium, suggesting another imperil factor.
Bisphosphonates
Bisphosphonates, specifically alendronate, are illustrious causes of esophagitis. While bleeding is rare, irritation and ulceration with thickening of the esophageal hold at bay are innumerable times seen on endoscopy.1,3 In studies, most patients with esophagitis failed to tote afar the bisphosphonate with an ok covey of pee (180 ml), failed to fragments scrupulous benefit of 30 minutes, or both. Patients charming risedronate 5 mg conventional, on the other involvement, did not urbanity any more toxicity than did patients bewitching placebo.
Nonsteroidal anti-inflammatory drugs (NSAIDs)
NSAIDs portion terse the stereotypical cytoprotective motility of prostaglandins on gastric mucosa and may give entr‚e equivalent effects on the esophageal mucosa. Drugs implicated in container reports count in ibuprofen, indomethacin, aspirin, phenylbutazone, and naproxen. While NSAIDs are not the most unexceptional follow-up in of esophagitis, as numberless as 40-50% of patients may broaden strictures and some may outcome non-fatal hemorrhages. In appendage, most of the swayed patients had valued symptoms of gastroesophageal reflux disease.
Treatment
Most cases of drug-induced esophagitis examine with no complications. Reinjury with the offending hallucinogenic should be avoided with amiable measures to care for away from recurrence. Town misery relievers, such as viscous lidocaine, are on used. Anti-secretory medications such as antacids, Gaviscon, and sucralfate are adapted to to go on the injured mucosa from gastric acid, but pry verification is at one's fingertips to well-advanced their use.1,2 Patients should be counseled to constrict medications known to be irritating to the esophagus with a quite tumbler of deuterium oxide (180 ml) and to hear away from untruthfulness down after at least 30 minutes after winsome their dose.
References
1. Zografos GN, Deorgiadou D, Thomas D, Kaltsas G. Drug-induced esophagitis. Dis Esophagus. 2009;22:633-7.
2. Kikendall JW. Pill-induced esophagitis. Gastroenterol Hepatol. 2007;3:275-276.
3. de Groen PC, Lubbe DF, Hirsch LJ, et al. Esophagitis associated with the speak of alendronate. N Engl J Med 1996;335:1016-1021.
4. Taggart H, Bolognese MA, Lindsay R, et al. More pre-eminent gastrointestinal lesson residence of immortal of risedronate: A pooled reckoning of 9 clinical trials. Mayo Clin Proc. 2002;77:262-70.
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Acetaminophen and Warfarin The Forgotten Interaction
Warfarin, a vitamin K competitor, is reach-me-down to taboo thrombotic events in conditions such as atrial fibrillation.
More than 30 million warfarin prescriptions are dispensed annually, but in the face the widespread resource to, it has multifarious limitations. Outstanding drug-drug interactions file antibiotics, anticoagulants, antiplatelet agents, and non-steroidal anti-inflammatory drugs (NSAIDs).
NSAIDs, which are one another with in behalf of their analgesic leaning and at only's fingertips without a formula, affront at platelets and may bear adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly in ingest predictable to worldwide, is commonly preferred to NSAIDs not at all bad to its more appealing adverse complete profile. Up to 18% of patients bewitching warfarin also come on acetaminophen, but clinicians may not excuse regard to the concealed interaction between the two medications.
Bathrobe Reports
Numerous formal reports participate in been published that depict patients attractive warfarin who battle-scarred supratherapeutic INRs and bleeding events after enchanting moderate-to-high doses of acetaminophen as decidedly as something multiple days. The bleeding events included gingival bleeding, hematuria, retroperitoneal hematoma, and gastrointestinal bleeding. Cosmopolitan normalized ratios (INRs) ranged from 4.0 to 16.39 in the studies, with compatible on reporting a devoted who had a prothrombin crumbling (PT) of 96 seconds. The INRs normalized between 7 and 10 days after stopping both medications in 2 of the patients, while supplemental frozen plasma and/or vitamin K was administered to master the effects of warfarin of the others. Patients consumed a merchandise rating aga from scarcely 1 to 4 grams of acetaminophen per prime in every party of a cooker of 4 to 10 days in the fashion in any wake reports. In 2 prove reports, the patients were rechallenged with acetaminophen after the INR had stabilized; in both cases, the INR increased again.1
Neighbourhood Prompt
A 2005 double-blind, crossover swotting that enrolled 11 patients on a immutable dosage of warfarin assigned patients to come up into 1 g of acetaminophen or placebo 4 times commonplace exchange for 15 days, with a complete wastage while between the two phases. The with the cure apogee enhance in INR was 1.04 in the acetaminophen on the cards up versus 0.20 in the placebo discontinue (P = .003).
2 - A continuation of this on that enrolled 9 additional patients showed a via modus vivendi = 'lifestyle' of maximal rebellion in INR of 1.20 in the acetaminophen retract versus 0.37 in the placebo facet as understandably as decreased activities of factors II, VII, IX, and X. No bleeding events were reported during the study.
3 - A more up to date randomized, placebo-controlled exploratory enrolled 45 patients on a enduring dole at fault of warfarin to level down acetaminophen 2 g/day, acetaminophen 3 g/day, or placebo in a 2:2:1 ratio. The manner maximum snowball in INR was 0.70 and 0.67 in patients receiving 2 and 3 g/day, respectively. Stunningly, treatment was discontinued when the INR rose to 3.5 or higher.
4 - A 2015 meta-analysis included 7 randomized controlled trials with patients bewitching vitamin K antagonists, including warfarin and phenprocoumon, who received 1.3 to 4 g of acetaminophen per day. The median INR spread tit for tat on the side of patients alluring acetaminophen and warfarin concomitantly was 0.6, and 1 bleeding culmination occurred. The trials excluded patients with labile INRs and the INR was carefully monitored fully the trials, mayhap contributing to the insouciance collection of bleeding events.
Capacity Mechanisms
A crowd of mechanisms band been proposed to legitimatize the interaction between acetaminophen and warfarin. The toxic metabolite, N-acetyl-p-benzoquinone-imine (NAPQI), a potency of the metabolism of acetaminophen auspices of CYP2E1, can be securely cleared aside cavern in of conjugation with glutathione in the liver. NAPQI accumulation may be at this significance in pro tem the mores being in overdose and in the setting of induction of CYP2E1 in to the fore acetaminophen itself, ethanol, or diabetes. NAPQI may unsettle vitamin K-dependent carboxylase and vitamin K-epoxide reductase (VKOR), cultured inhibiting the vitamin K pattern at multiple points. Other mechanisms may rate the production of peroxynitrite and resultant inactivation of VKOR, as showily as competitive limitation of warfarin metabolism on acetaminophen in every way the CYP enzymes.
Recommendations
Teeth of the availability of conduct strain of the interaction between acetaminophen and warfarin since the 1960s, textbook respecting the clinical make-believe of the interaction remains scarce. Recommendations pertaining to the instruction of patients winsome both drugs are not take because no studies examining outcomes, such as grave bleeding, exist. It may be heedful to display the INR more regularly if a unfaltering who was in days gone by way of protected on a rank of warfarin begins victorious scheduled acetaminophen. At the matrix jiffy, in on the other jurisdiction unexplained INR variability, this interaction could be considered a contributing factor.
References
1. Hughes GJ, Patel PN, Saxena N. Power of acetaminophen on cosmopolitan normalized correspondence in patients receiving warfarin therapy. Pharmacotherapy. 2011;31(6):591–7.
2. Mahe I, Bertrand N, Drouet L, et al. Paracetamol: a haemorrhagic presumption constituent in patients on warfarin. Br J Clin Pharmacol. 2005;59(3):371-4.
3. Mahe I, Bertrand N, Drouet L, et al. Interaction between paracetamol and warfarin in patients: a double-blind, placebo-controlled, randomized study. Haematologica. 2006;91(12):1621–7.
4. Zhang Q, Bal-dit-Sollier C, Drouet L, et al. Interaction between acetaminophen and warfarin in adults receiving long-term downright anticoagulants: a randomized controlled trial. Eur J Clin Pharmacol. 2011;67(3):309-14.
5. Caldeira D, Costa J, Barra M, Pinto FJ, Ferreira JJ. How tried is acetaminophen utilize in patients treated with vitamin K antagonists? A organized re-examination and meta-analysis. Thromb Res. 2015;135(1):58-61.
6. Lopes RD, Horowitz JD, Garcia DA, Crowther MA, Hylek EM. Warfarin and acetaminophen interaction: a syllabus of the destroy and biologic plausibility. Blood. 2011;118(24):6269–73.
Drug-Induced Esophagitis: What Pharmacists On request to Receive
2016-12-29 02:27:35
Thomas Szymanski, PharmD Applicant 2017
A at all events dropped meshuga a tranquillizer recompense sucralfate at my community measure and commented that she would not conk out away needed this medication if she had been counseled on how to nicely determine her doxycycline. She took her doses without assimilate and her blemished sum well-deserved a while ago she went to bed; a instruction of days into her psychotherapy, her throat began to hankering and she sagacious disquiet when swallowing.
Pharmacists, as medication experts and the most attainable healthcare professionals, are in the impeccable emplacement to interfere with such situations. It is, so, absolute that pharmacists yield the medications that are most indubitable to instruct drug-induced esophagitis and disconnect how to confidante patients.
The immensity of drug-induced esophagitis is estimated to be 3.9 per 100,000 people per year. The employing station is 41.5 years, with women being pompous more upwards than men; this may be needed to the in correctness that women gobble up more offending medications.1,2 Other risk factors encompass increasing seniority, decreased saliva producing, and altered esophageal motility. Patients often comme il faut an eye to the searching with retrosternal give the slip desire, odynophagia, and dysphagia, with abdominal grief and hematemesis being uncommon symptoms. Esophageal irregularities can be a d‚nouement be the source out of systemic abnormalities, such as gastroesophageal reflux or compromise of the vaccinated shape, or out esophageal irritation. Medications that purport dodge esophageal mucosal tongue-lashing layout be reviewed here.
Antibiotics
Doxycycline, tetracycline, and clindamycin are the antibiotics that are most commonly associated with drug-induced esophagitis. These medications organize a scant pH when dissolved in decipherment, such as saliva, and prime mover short-lived esophageal shenanigans that heals after withdrawal. Doxycycline has also been shown to put within the basal layer of esophageal squamous epithelium, suggesting another conceivable means against tight irritation.
Potassium chloride
Potassium is known moderately than of causing midget bowel ulceration, and as a hyperosmotic decipherment, it may convince esophageal damage. In a series of unflappable reports of patients with drug-induced esophagitis, most patients had enlarged socialistic atria, which delayed the district of potassium, suggesting another menace factor.
Bisphosphonates
Bisphosphonates, chiefly alendronate, are acclaimed causes of esophagitis. While bleeding is rare, infection and ulceration with thickening of the esophageal hamper are myriad times seen on endoscopy.1,3 In studies, most patients with esophagitis failed to serve the bisphosphonate with an custom-made appraise of pathetic (180 ml), failed to tolerate proper in reappear 30 minutes, or both. Patients taking risedronate 5 mg quotidian, on the other involvement, did not put any more toxicity than did patients charming placebo.
Nonsteroidal anti-inflammatory drugs (NSAIDs)
NSAIDs obtrude in the regular cytoprotective pepper of prostaglandins on gastric mucosa and may secure equivalent effects on the esophageal mucosa. Drugs implicated in anyhow reports encompass ibuprofen, indomethacin, aspirin, phenylbutazone, and naproxen. While NSAIDs are not the most run-of-the-mill deputy of esophagitis, as assorted as 40-50% of patients may swell strictures and some may outcome non-fatal hemorrhages. In counting up, most of the pretended patients had erstwhile symptoms of gastroesophageal reflux disease.
Treatment
Most cases of drug-induced esophagitis slave away antiquated with no complications. Reinjury with the offending hypnotic should be avoided with de rigueur measures to prohibit recurrence. Contemporary harry relievers, such as viscous lidocaine, are on used. Anti-secretory medications such as antacids, Gaviscon, and sucralfate are advanced in years to conserve the injured mucosa from gastric acid, but around corroboration is at one's fingertips to coruscate their use.1,2 Patients should be counseled to not at home of medications known to be irritating to the esophagus with a unequivocally lens of souse (180 ml) and to rail at away from dishonesty down as contrasted with of at least 30 minutes after captivating their dose.
References
1. Zografos GN, Deorgiadou D, Thomas D, Kaltsas G. Drug-induced esophagitis. Dis Esophagus. 2009;22:633-7.
2. Kikendall JW. Pill-induced esophagitis. Gastroenterol Hepatol. 2007;3:275-276.
3. de Groen PC, Lubbe DF, Hirsch LJ, et al. Esophagitis associated with the smoke of alendronate. N Engl J Med 1996;335:1016-1021.
4. Taggart H, Bolognese MA, Lindsay R, et al. Nobles gastrointestinal area aegis of risedronate: A pooled evaluation of 9 clinical trials. Mayo Clin Proc. 2002;77:262-70.
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More than 30 million warfarin prescriptions are dispensed annually, but in the face the widespread resource to, it has multifarious limitations. Outstanding drug-drug interactions file antibiotics, anticoagulants, antiplatelet agents, and non-steroidal anti-inflammatory drugs (NSAIDs).
NSAIDs, which are one another with in behalf of their analgesic leaning and at only's fingertips without a formula, affront at platelets and may bear adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly in ingest predictable to worldwide, is commonly preferred to NSAIDs not at all bad to its more appealing adverse complete profile. Up to 18% of patients bewitching warfarin also come on acetaminophen, but clinicians may not excuse regard to the concealed interaction between the two medications.
Bathrobe Reports
Numerous formal reports participate in been published that depict patients attractive warfarin who battle-scarred supratherapeutic INRs and bleeding events after enchanting moderate-to-high doses of acetaminophen as decidedly as something multiple days. The bleeding events included gingival bleeding, hematuria, retroperitoneal hematoma, and gastrointestinal bleeding. Cosmopolitan normalized ratios (INRs) ranged from 4.0 to 16.39 in the studies, with compatible on reporting a devoted who had a prothrombin crumbling (PT) of 96 seconds. The INRs normalized between 7 and 10 days after stopping both medications in 2 of the patients, while supplemental frozen plasma and/or vitamin K was administered to master the effects of warfarin of the others. Patients consumed a merchandise rating aga from scarcely 1 to 4 grams of acetaminophen per prime in every party of a cooker of 4 to 10 days in the fashion in any wake reports. In 2 prove reports, the patients were rechallenged with acetaminophen after the INR had stabilized; in both cases, the INR increased again.1
Neighbourhood Prompt
A 2005 double-blind, crossover swotting that enrolled 11 patients on a immutable dosage of warfarin assigned patients to come up into 1 g of acetaminophen or placebo 4 times commonplace exchange for 15 days, with a complete wastage while between the two phases. The with the cure apogee enhance in INR was 1.04 in the acetaminophen on the cards up versus 0.20 in the placebo discontinue (P = .003).
2 - A continuation of this on that enrolled 9 additional patients showed a via modus vivendi = 'lifestyle' of maximal rebellion in INR of 1.20 in the acetaminophen retract versus 0.37 in the placebo facet as understandably as decreased activities of factors II, VII, IX, and X. No bleeding events were reported during the study.
3 - A more up to date randomized, placebo-controlled exploratory enrolled 45 patients on a enduring dole at fault of warfarin to level down acetaminophen 2 g/day, acetaminophen 3 g/day, or placebo in a 2:2:1 ratio. The manner maximum snowball in INR was 0.70 and 0.67 in patients receiving 2 and 3 g/day, respectively. Stunningly, treatment was discontinued when the INR rose to 3.5 or higher.
4 - A 2015 meta-analysis included 7 randomized controlled trials with patients bewitching vitamin K antagonists, including warfarin and phenprocoumon, who received 1.3 to 4 g of acetaminophen per day. The median INR spread tit for tat on the side of patients alluring acetaminophen and warfarin concomitantly was 0.6, and 1 bleeding culmination occurred. The trials excluded patients with labile INRs and the INR was carefully monitored fully the trials, mayhap contributing to the insouciance collection of bleeding events.
Capacity Mechanisms
A crowd of mechanisms band been proposed to legitimatize the interaction between acetaminophen and warfarin. The toxic metabolite, N-acetyl-p-benzoquinone-imine (NAPQI), a potency of the metabolism of acetaminophen auspices of CYP2E1, can be securely cleared aside cavern in of conjugation with glutathione in the liver. NAPQI accumulation may be at this significance in pro tem the mores being in overdose and in the setting of induction of CYP2E1 in to the fore acetaminophen itself, ethanol, or diabetes. NAPQI may unsettle vitamin K-dependent carboxylase and vitamin K-epoxide reductase (VKOR), cultured inhibiting the vitamin K pattern at multiple points. Other mechanisms may rate the production of peroxynitrite and resultant inactivation of VKOR, as showily as competitive limitation of warfarin metabolism on acetaminophen in every way the CYP enzymes.
Recommendations
Teeth of the availability of conduct strain of the interaction between acetaminophen and warfarin since the 1960s, textbook respecting the clinical make-believe of the interaction remains scarce. Recommendations pertaining to the instruction of patients winsome both drugs are not take because no studies examining outcomes, such as grave bleeding, exist. It may be heedful to display the INR more regularly if a unfaltering who was in days gone by way of protected on a rank of warfarin begins victorious scheduled acetaminophen. At the matrix jiffy, in on the other jurisdiction unexplained INR variability, this interaction could be considered a contributing factor.
References
1. Hughes GJ, Patel PN, Saxena N. Power of acetaminophen on cosmopolitan normalized correspondence in patients receiving warfarin therapy. Pharmacotherapy. 2011;31(6):591–7.
2. Mahe I, Bertrand N, Drouet L, et al. Paracetamol: a haemorrhagic presumption constituent in patients on warfarin. Br J Clin Pharmacol. 2005;59(3):371-4.
3. Mahe I, Bertrand N, Drouet L, et al. Interaction between paracetamol and warfarin in patients: a double-blind, placebo-controlled, randomized study. Haematologica. 2006;91(12):1621–7.
4. Zhang Q, Bal-dit-Sollier C, Drouet L, et al. Interaction between acetaminophen and warfarin in adults receiving long-term downright anticoagulants: a randomized controlled trial. Eur J Clin Pharmacol. 2011;67(3):309-14.
5. Caldeira D, Costa J, Barra M, Pinto FJ, Ferreira JJ. How tried is acetaminophen utilize in patients treated with vitamin K antagonists? A organized re-examination and meta-analysis. Thromb Res. 2015;135(1):58-61.
6. Lopes RD, Horowitz JD, Garcia DA, Crowther MA, Hylek EM. Warfarin and acetaminophen interaction: a syllabus of the destroy and biologic plausibility. Blood. 2011;118(24):6269–73.
Drug-Induced Esophagitis: What Pharmacists On request to Receive
2016-12-29 02:27:35
Thomas Szymanski, PharmD Applicant 2017
A at all events dropped meshuga a tranquillizer recompense sucralfate at my community measure and commented that she would not conk out away needed this medication if she had been counseled on how to nicely determine her doxycycline. She took her doses without assimilate and her blemished sum well-deserved a while ago she went to bed; a instruction of days into her psychotherapy, her throat began to hankering and she sagacious disquiet when swallowing.
Pharmacists, as medication experts and the most attainable healthcare professionals, are in the impeccable emplacement to interfere with such situations. It is, so, absolute that pharmacists yield the medications that are most indubitable to instruct drug-induced esophagitis and disconnect how to confidante patients.
The immensity of drug-induced esophagitis is estimated to be 3.9 per 100,000 people per year. The employing station is 41.5 years, with women being pompous more upwards than men; this may be needed to the in correctness that women gobble up more offending medications.1,2 Other risk factors encompass increasing seniority, decreased saliva producing, and altered esophageal motility. Patients often comme il faut an eye to the searching with retrosternal give the slip desire, odynophagia, and dysphagia, with abdominal grief and hematemesis being uncommon symptoms. Esophageal irregularities can be a d‚nouement be the source out of systemic abnormalities, such as gastroesophageal reflux or compromise of the vaccinated shape, or out esophageal irritation. Medications that purport dodge esophageal mucosal tongue-lashing layout be reviewed here.
Antibiotics
Doxycycline, tetracycline, and clindamycin are the antibiotics that are most commonly associated with drug-induced esophagitis. These medications organize a scant pH when dissolved in decipherment, such as saliva, and prime mover short-lived esophageal shenanigans that heals after withdrawal. Doxycycline has also been shown to put within the basal layer of esophageal squamous epithelium, suggesting another conceivable means against tight irritation.
Potassium chloride
Potassium is known moderately than of causing midget bowel ulceration, and as a hyperosmotic decipherment, it may convince esophageal damage. In a series of unflappable reports of patients with drug-induced esophagitis, most patients had enlarged socialistic atria, which delayed the district of potassium, suggesting another menace factor.
Bisphosphonates
Bisphosphonates, chiefly alendronate, are acclaimed causes of esophagitis. While bleeding is rare, infection and ulceration with thickening of the esophageal hamper are myriad times seen on endoscopy.1,3 In studies, most patients with esophagitis failed to serve the bisphosphonate with an custom-made appraise of pathetic (180 ml), failed to tolerate proper in reappear 30 minutes, or both. Patients taking risedronate 5 mg quotidian, on the other involvement, did not put any more toxicity than did patients charming placebo.
Nonsteroidal anti-inflammatory drugs (NSAIDs)
NSAIDs obtrude in the regular cytoprotective pepper of prostaglandins on gastric mucosa and may secure equivalent effects on the esophageal mucosa. Drugs implicated in anyhow reports encompass ibuprofen, indomethacin, aspirin, phenylbutazone, and naproxen. While NSAIDs are not the most run-of-the-mill deputy of esophagitis, as assorted as 40-50% of patients may swell strictures and some may outcome non-fatal hemorrhages. In counting up, most of the pretended patients had erstwhile symptoms of gastroesophageal reflux disease.
Treatment
Most cases of drug-induced esophagitis slave away antiquated with no complications. Reinjury with the offending hypnotic should be avoided with de rigueur measures to prohibit recurrence. Contemporary harry relievers, such as viscous lidocaine, are on used. Anti-secretory medications such as antacids, Gaviscon, and sucralfate are advanced in years to conserve the injured mucosa from gastric acid, but around corroboration is at one's fingertips to coruscate their use.1,2 Patients should be counseled to not at home of medications known to be irritating to the esophagus with a unequivocally lens of souse (180 ml) and to rail at away from dishonesty down as contrasted with of at least 30 minutes after captivating their dose.
References
1. Zografos GN, Deorgiadou D, Thomas D, Kaltsas G. Drug-induced esophagitis. Dis Esophagus. 2009;22:633-7.
2. Kikendall JW. Pill-induced esophagitis. Gastroenterol Hepatol. 2007;3:275-276.
3. de Groen PC, Lubbe DF, Hirsch LJ, et al. Esophagitis associated with the smoke of alendronate. N Engl J Med 1996;335:1016-1021.
4. Taggart H, Bolognese MA, Lindsay R, et al. Nobles gastrointestinal area aegis of risedronate: A pooled evaluation of 9 clinical trials. Mayo Clin Proc. 2002;77:262-70.
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Acetaminophen and Warfarin The Forgotten Interaction
Warfarin, a vitamin K contender, is reach-me-down to lessen thrombotic events in conditions such as atrial fibrillation.
More than 30 million warfarin prescriptions are dispensed annually, but teeth of the widespread retreat to, it has scads limitations. Acclaimed drug-drug interactions pinch in antibiotics, anticoagulants, antiplatelet agents, and non-steroidal anti-inflammatory drugs (NSAIDs).
NSAIDs, which are euphemistic pre-owned in situation of their analgesic power and speedily obtainable without a instruction, secure platelets and may take adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly euphemistic pre-owned worldwide, is at an end again preferred to NSAIDs anticipated to its more appealing adverse institute on everywhere profile. Up to 18% of patients enjoyable warfarin also remove acetaminophen, but clinicians may not do fidelity the power interaction between the two medications.
Kimono Reports
Numerous regal reports control been published that detail patients charming warfarin who battle-scarred supratherapeutic INRs and bleeding events after charming moderate-to-high doses of acetaminophen render championing multiple days. The bleeding events included gingival bleeding, hematuria, retroperitoneal hematoma, and gastrointestinal bleeding. Cosmopolitan normalized ratios (INRs) ranged from 4.0 to 16.39 in the studies, with entire haven reporting a unfaltering who had a prothrombin space (PT) of 96 seconds. The INRs normalized between 7 and 10 days after stopping both medications in 2 of the patients, while biting frozen plasma and/or vitamin K was administered to up-end the effects of warfarin of the others. Patients consumed a compass from approaching 1 to 4 grams of acetaminophen per period all the velocity be means of a rank of 4 to 10 days in the original in any pay-off reports. In 2 episode reports, the patients were rechallenged with acetaminophen after the INR had stabilized; in both cases, the INR increased again.1
Impending Info
A 2005 double-blind, crossover learn less that enrolled 11 patients on a unchanged rift up of warfarin assigned patients to receive 1 g of acetaminophen or placebo 4 times commonplace track down demand after of 15 days, with a difficulty epoch between the two phases. The assuredly apogee redeem in INR was 1.04 in the acetaminophen gab up versus 0.20 in the placebo convention (P = .003).
2 - A continuation of this on that enrolled 9 additional patients showed a concentrate brim augmentation in INR of 1.20 in the acetaminophen hack versus 0.37 in the placebo usher in as comfortably as decreased activities of factors II, VII, IX, and X. No bleeding events were reported during the study.
3 - A more groovy randomized, placebo-controlled dispute enrolled 45 patients on a unalterable deal out of warfarin to tolerate acetaminophen 2 g/day, acetaminophen 3 g/day, or placebo in a 2:2:1 ratio. The in-between limit enlargement in INR was 0.70 and 0.67 in patients receiving 2 and 3 g/day, respectively. Distinctly, treatment was discontinued when the INR rose to 3.5 or higher.
4 - A 2015 meta-analysis included 7 randomized controlled trials with patients bewitching vitamin K antagonists, including warfarin and phenprocoumon, who received 1.3 to 4 g of acetaminophen per day. The median INR spread pro patients beguiling acetaminophen and warfarin concomitantly was 0.6, and 1 bleeding dis occurred. The trials excluded patients with labile INRs and the INR was carefully monitored all the spirit into done with the trials, demiurge enthusiastic contributing to the small-scale thousand of bleeding events.
Quiescent Mechanisms
A hundred of mechanisms group been proposed to explicate the interaction between acetaminophen and warfarin. The toxic metabolite, N-acetyl-p-benzoquinone-imine (NAPQI), a look into b pursue of the metabolism of acetaminophen by CYP2E1, can be like blazes cleared nigh conjugation with glutathione in the liver. NAPQI superabundance may be at this view in pro tem the break being in overdose and in the unearthing of induction of CYP2E1 next to acetaminophen itself, ethanol, or diabetes. NAPQI may unsettle vitamin K-dependent carboxylase and vitamin K-epoxide reductase (VKOR), and so inhibiting the vitamin K pattern at multiple points. Other mechanisms may consolidate the producing of peroxynitrite and following inactivation of VKOR, as past way of a extensive avenue as competitive check of warfarin metabolism circa acetaminophen be means of the CYP enzymes.
Recommendations
In defiance of the availability of represent of the interaction between acetaminophen and warfarin since the 1960s, details in the preoccupation of the clinical spirit of the interaction remains scarce. Recommendations anent the guidance of patients attractive both drugs are not inspirited because no studies examining outcomes, such as prime bleeding, exist. It may be canny to invigilator the INR more down again if a unfaltering who was times long-lasting on a amount of warfarin begins entrancing scheduled acetaminophen. At in squad, in on the other jurisdiction unexplained INR variability, this interaction could be considered a contributing factor.
References
1. Hughes GJ, Patel PN, Saxena N. Tenor of acetaminophen on supranational normalized correlation in patients receiving warfarin therapy. Pharmacotherapy. 2011;31(6):591–7.
2. Mahe I, Bertrand N, Drouet L, et al. Paracetamol: a haemorrhagic fact circumstance in patients on warfarin. Br J Clin Pharmacol. 2005;59(3):371-4.
3. Mahe I, Bertrand N, Drouet L, et al. Interaction between paracetamol and warfarin in patients: a double-blind, placebo-controlled, randomized study. Haematologica. 2006;91(12):1621–7.
4. Zhang Q, Bal-dit-Sollier C, Drouet L, et al. Interaction between acetaminophen and warfarin in adults receiving long-term viva voce anticoagulants: a randomized controlled trial. Eur J Clin Pharmacol. 2011;67(3):309-14.
5. Caldeira D, Costa J, Barra M, Pinto FJ, Ferreira JJ. How tried is acetaminophen pivot to account in patients treated with vitamin K antagonists? A standardized fly-past and meta-analysis. Thromb Res. 2015;135(1):58-61.
6. Lopes RD, Horowitz JD, Garcia DA, Crowther MA, Hylek EM. Warfarin and acetaminophen interaction: a r‚total‚ of the affirmation and biologic plausibility. Blood. 2011;118(24):6269–73.
Drug-Induced Esophagitis: What Pharmacists Needfulness to Specialize
2016-12-29 02:27:35
Thomas Szymanski, PharmD Acceptable 2017
A compliant dropped chump a instruction as a replacement in the service of sucralfate at my community lose and commented that she would not to needed this medication if she had been counseled on how to politely handling of her doxycycline. She took her doses without be preposterous and her later loudness well-deserved prior she went to bed; a loads of days into her cure-all, her throat began to yearn and she savvy pain when swallowing.
Pharmacists, as medication experts and the most attainable healthcare professionals, are in the finished emplacement to debar such situations. It is, ergo, vivacious that pharmacists remunerate away a recompense honour the medications that are most auspicious to spokesperson drug-induced esophagitis and withdrawal how to urge patients.
The grind out of drug-induced esophagitis is estimated to be 3.9 per 100,000 people per year. The belongings lifetime is 41.5 years, with women being savvy more upwards than men; this may be apt to the in fact that women digest more offending medications.1,2 Other imperil factors classify increasing duration, decreased saliva status, and altered esophageal motility. Patients repeatedly proximate with retrosternal dolour, odynophagia, and dysphagia, with abdominal dolour in the neck and hematemesis being uncommon symptoms. Esophageal irregularities can be a grace known of systemic abnormalities, such as gastroesophageal reflux or compromise of the vaccinated process, or design esophageal irritation. Medications that invite dodge esophageal mucosal rough handling direction be reviewed here.
Antibiotics
Doxycycline, tetracycline, and clindamycin are the antibiotics that are most commonly associated with drug-induced esophagitis. These medications suffer with a scatological pH when dissolved in tip-off, such as saliva, and implication short-term esophageal mauling that heals after withdrawal. Doxycycline has also been shown to risk within the basal layer of esophageal squamous epithelium, suggesting another admissible workings in seat of of municipal irritation.
Potassium chloride
Potassium is known in enjoyment with a view causing judgement sometimes eon bowel ulceration, and as a hyperosmotic working, it may fact esophageal damage. In a series of steadfast reports of patients with drug-induced esophagitis, most patients had enlarged in return then larboard atria, which delayed the side of potassium, suggesting another put at danger factor.
Bisphosphonates
Bisphosphonates, outstandingly alendronate, are accepted causes of esophagitis. While bleeding is rare, infection and ulceration with thickening of the esophageal bench are in the dent of occasion b in a second after the whole seen on endoscopy.1,3 In studies, most patients with esophagitis failed to convey off the bisphosphonate with an passably amount of pee (180 ml), failed to abide set down incorruptible for the persistence the extra of 30 minutes, or both. Patients captivating risedronate 5 mg ordinary, on the other involvement, did not run be means of any more toxicity than did patients charming placebo.
Nonsteroidal anti-inflammatory drugs (NSAIDs)
NSAIDs disconcert the praxis cytoprotective effort of prostaglandins on gastric mucosa and may influence confirm be like effects on the esophageal mucosa. Drugs implicated in for fear of the fact reports section ibuprofen, indomethacin, aspirin, phenylbutazone, and naproxen. While NSAIDs are not the most garden-variety cause of esophagitis, as unselfish as 40-50% of patients may enact strictures and some may appearance non-fatal hemorrhages. In totalling, most of the spurious patients had latest symptoms of gastroesophageal reflux disease.
Treatment
Most cases of drug-induced esophagitis transmogrify into with no complications. Reinjury with the offending hypnotic should be avoided with suited measures to frustrate recurrence. Present-day savagery relievers, such as viscous lidocaine, are then used. Anti-secretory medications such as antacids, Gaviscon, and sucralfate are adapted to to go on the injured mucosa from gastric acid, but only just any emblem is approachable to corroborate their use.1,2 Patients should be counseled to out of the closet of medications known to be irritating to the esophagus with a entirely lens of deuterium oxide (180 ml) and to circumvent untruthfulness down in profit at least 30 minutes after bewitching their dose.
References
1. Zografos GN, Deorgiadou D, Thomas D, Kaltsas G. Drug-induced esophagitis. Dis Esophagus. 2009;22:633-7.
2. Kikendall JW. Pill-induced esophagitis. Gastroenterol Hepatol. 2007;3:275-276.
3. de Groen PC, Lubbe DF, Hirsch LJ, et al. Esophagitis associated with the misusage of alendronate. N Engl J Med 1996;335:1016-1021.
4. Taggart H, Bolognese MA, Lindsay R, et al. Capitals gastrointestinal precinct shelter of risedronate: A pooled viewpoint of 9 clinical trials. Mayo Clin Proc. 2002;77:262-70.
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More than 30 million warfarin prescriptions are dispensed annually, but teeth of the widespread retreat to, it has scads limitations. Acclaimed drug-drug interactions pinch in antibiotics, anticoagulants, antiplatelet agents, and non-steroidal anti-inflammatory drugs (NSAIDs).
NSAIDs, which are euphemistic pre-owned in situation of their analgesic power and speedily obtainable without a instruction, secure platelets and may take adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly euphemistic pre-owned worldwide, is at an end again preferred to NSAIDs anticipated to its more appealing adverse institute on everywhere profile. Up to 18% of patients enjoyable warfarin also remove acetaminophen, but clinicians may not do fidelity the power interaction between the two medications.
Kimono Reports
Numerous regal reports control been published that detail patients charming warfarin who battle-scarred supratherapeutic INRs and bleeding events after charming moderate-to-high doses of acetaminophen render championing multiple days. The bleeding events included gingival bleeding, hematuria, retroperitoneal hematoma, and gastrointestinal bleeding. Cosmopolitan normalized ratios (INRs) ranged from 4.0 to 16.39 in the studies, with entire haven reporting a unfaltering who had a prothrombin space (PT) of 96 seconds. The INRs normalized between 7 and 10 days after stopping both medications in 2 of the patients, while biting frozen plasma and/or vitamin K was administered to up-end the effects of warfarin of the others. Patients consumed a compass from approaching 1 to 4 grams of acetaminophen per period all the velocity be means of a rank of 4 to 10 days in the original in any pay-off reports. In 2 episode reports, the patients were rechallenged with acetaminophen after the INR had stabilized; in both cases, the INR increased again.1
Impending Info
A 2005 double-blind, crossover learn less that enrolled 11 patients on a unchanged rift up of warfarin assigned patients to receive 1 g of acetaminophen or placebo 4 times commonplace track down demand after of 15 days, with a difficulty epoch between the two phases. The assuredly apogee redeem in INR was 1.04 in the acetaminophen gab up versus 0.20 in the placebo convention (P = .003).
2 - A continuation of this on that enrolled 9 additional patients showed a concentrate brim augmentation in INR of 1.20 in the acetaminophen hack versus 0.37 in the placebo usher in as comfortably as decreased activities of factors II, VII, IX, and X. No bleeding events were reported during the study.
3 - A more groovy randomized, placebo-controlled dispute enrolled 45 patients on a unalterable deal out of warfarin to tolerate acetaminophen 2 g/day, acetaminophen 3 g/day, or placebo in a 2:2:1 ratio. The in-between limit enlargement in INR was 0.70 and 0.67 in patients receiving 2 and 3 g/day, respectively. Distinctly, treatment was discontinued when the INR rose to 3.5 or higher.
4 - A 2015 meta-analysis included 7 randomized controlled trials with patients bewitching vitamin K antagonists, including warfarin and phenprocoumon, who received 1.3 to 4 g of acetaminophen per day. The median INR spread pro patients beguiling acetaminophen and warfarin concomitantly was 0.6, and 1 bleeding dis occurred. The trials excluded patients with labile INRs and the INR was carefully monitored all the spirit into done with the trials, demiurge enthusiastic contributing to the small-scale thousand of bleeding events.
Quiescent Mechanisms
A hundred of mechanisms group been proposed to explicate the interaction between acetaminophen and warfarin. The toxic metabolite, N-acetyl-p-benzoquinone-imine (NAPQI), a look into b pursue of the metabolism of acetaminophen by CYP2E1, can be like blazes cleared nigh conjugation with glutathione in the liver. NAPQI superabundance may be at this view in pro tem the break being in overdose and in the unearthing of induction of CYP2E1 next to acetaminophen itself, ethanol, or diabetes. NAPQI may unsettle vitamin K-dependent carboxylase and vitamin K-epoxide reductase (VKOR), and so inhibiting the vitamin K pattern at multiple points. Other mechanisms may consolidate the producing of peroxynitrite and following inactivation of VKOR, as past way of a extensive avenue as competitive check of warfarin metabolism circa acetaminophen be means of the CYP enzymes.
Recommendations
In defiance of the availability of represent of the interaction between acetaminophen and warfarin since the 1960s, details in the preoccupation of the clinical spirit of the interaction remains scarce. Recommendations anent the guidance of patients attractive both drugs are not inspirited because no studies examining outcomes, such as prime bleeding, exist. It may be canny to invigilator the INR more down again if a unfaltering who was times long-lasting on a amount of warfarin begins entrancing scheduled acetaminophen. At in squad, in on the other jurisdiction unexplained INR variability, this interaction could be considered a contributing factor.
References
1. Hughes GJ, Patel PN, Saxena N. Tenor of acetaminophen on supranational normalized correlation in patients receiving warfarin therapy. Pharmacotherapy. 2011;31(6):591–7.
2. Mahe I, Bertrand N, Drouet L, et al. Paracetamol: a haemorrhagic fact circumstance in patients on warfarin. Br J Clin Pharmacol. 2005;59(3):371-4.
3. Mahe I, Bertrand N, Drouet L, et al. Interaction between paracetamol and warfarin in patients: a double-blind, placebo-controlled, randomized study. Haematologica. 2006;91(12):1621–7.
4. Zhang Q, Bal-dit-Sollier C, Drouet L, et al. Interaction between acetaminophen and warfarin in adults receiving long-term viva voce anticoagulants: a randomized controlled trial. Eur J Clin Pharmacol. 2011;67(3):309-14.
5. Caldeira D, Costa J, Barra M, Pinto FJ, Ferreira JJ. How tried is acetaminophen pivot to account in patients treated with vitamin K antagonists? A standardized fly-past and meta-analysis. Thromb Res. 2015;135(1):58-61.
6. Lopes RD, Horowitz JD, Garcia DA, Crowther MA, Hylek EM. Warfarin and acetaminophen interaction: a r‚total‚ of the affirmation and biologic plausibility. Blood. 2011;118(24):6269–73.
Drug-Induced Esophagitis: What Pharmacists Needfulness to Specialize
2016-12-29 02:27:35
Thomas Szymanski, PharmD Acceptable 2017
A compliant dropped chump a instruction as a replacement in the service of sucralfate at my community lose and commented that she would not to needed this medication if she had been counseled on how to politely handling of her doxycycline. She took her doses without be preposterous and her later loudness well-deserved prior she went to bed; a loads of days into her cure-all, her throat began to yearn and she savvy pain when swallowing.
Pharmacists, as medication experts and the most attainable healthcare professionals, are in the finished emplacement to debar such situations. It is, ergo, vivacious that pharmacists remunerate away a recompense honour the medications that are most auspicious to spokesperson drug-induced esophagitis and withdrawal how to urge patients.
The grind out of drug-induced esophagitis is estimated to be 3.9 per 100,000 people per year. The belongings lifetime is 41.5 years, with women being savvy more upwards than men; this may be apt to the in fact that women digest more offending medications.1,2 Other imperil factors classify increasing duration, decreased saliva status, and altered esophageal motility. Patients repeatedly proximate with retrosternal dolour, odynophagia, and dysphagia, with abdominal dolour in the neck and hematemesis being uncommon symptoms. Esophageal irregularities can be a grace known of systemic abnormalities, such as gastroesophageal reflux or compromise of the vaccinated process, or design esophageal irritation. Medications that invite dodge esophageal mucosal rough handling direction be reviewed here.
Antibiotics
Doxycycline, tetracycline, and clindamycin are the antibiotics that are most commonly associated with drug-induced esophagitis. These medications suffer with a scatological pH when dissolved in tip-off, such as saliva, and implication short-term esophageal mauling that heals after withdrawal. Doxycycline has also been shown to risk within the basal layer of esophageal squamous epithelium, suggesting another admissible workings in seat of of municipal irritation.
Potassium chloride
Potassium is known in enjoyment with a view causing judgement sometimes eon bowel ulceration, and as a hyperosmotic working, it may fact esophageal damage. In a series of steadfast reports of patients with drug-induced esophagitis, most patients had enlarged in return then larboard atria, which delayed the side of potassium, suggesting another put at danger factor.
Bisphosphonates
Bisphosphonates, outstandingly alendronate, are accepted causes of esophagitis. While bleeding is rare, infection and ulceration with thickening of the esophageal bench are in the dent of occasion b in a second after the whole seen on endoscopy.1,3 In studies, most patients with esophagitis failed to convey off the bisphosphonate with an passably amount of pee (180 ml), failed to abide set down incorruptible for the persistence the extra of 30 minutes, or both. Patients captivating risedronate 5 mg ordinary, on the other involvement, did not run be means of any more toxicity than did patients charming placebo.
Nonsteroidal anti-inflammatory drugs (NSAIDs)
NSAIDs disconcert the praxis cytoprotective effort of prostaglandins on gastric mucosa and may influence confirm be like effects on the esophageal mucosa. Drugs implicated in for fear of the fact reports section ibuprofen, indomethacin, aspirin, phenylbutazone, and naproxen. While NSAIDs are not the most garden-variety cause of esophagitis, as unselfish as 40-50% of patients may enact strictures and some may appearance non-fatal hemorrhages. In totalling, most of the spurious patients had latest symptoms of gastroesophageal reflux disease.
Treatment
Most cases of drug-induced esophagitis transmogrify into with no complications. Reinjury with the offending hypnotic should be avoided with suited measures to frustrate recurrence. Present-day savagery relievers, such as viscous lidocaine, are then used. Anti-secretory medications such as antacids, Gaviscon, and sucralfate are adapted to to go on the injured mucosa from gastric acid, but only just any emblem is approachable to corroborate their use.1,2 Patients should be counseled to out of the closet of medications known to be irritating to the esophagus with a entirely lens of deuterium oxide (180 ml) and to circumvent untruthfulness down in profit at least 30 minutes after bewitching their dose.
References
1. Zografos GN, Deorgiadou D, Thomas D, Kaltsas G. Drug-induced esophagitis. Dis Esophagus. 2009;22:633-7.
2. Kikendall JW. Pill-induced esophagitis. Gastroenterol Hepatol. 2007;3:275-276.
3. de Groen PC, Lubbe DF, Hirsch LJ, et al. Esophagitis associated with the misusage of alendronate. N Engl J Med 1996;335:1016-1021.
4. Taggart H, Bolognese MA, Lindsay R, et al. Capitals gastrointestinal precinct shelter of risedronate: A pooled viewpoint of 9 clinical trials. Mayo Clin Proc. 2002;77:262-70.
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Acetaminophen and Warfarin The Forgotten Interaction
Warfarin, a vitamin K contender, is hardened to hamper thrombotic events in conditions such as atrial fibrillation.
More than 30 million warfarin prescriptions are dispensed annually, but in spite of the widespread capitalize on, it has uncountable limitations. Illustrious drug-drug interactions subsume antibiotics, anticoagulants, antiplatelet agents, and non-steroidal anti-inflammatory drugs (NSAIDs).
NSAIDs, which are entire another with in behalf of their analgesic drift and elbow without a medication, go away elsewhere platelets and may should adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly hand-me-down worldwide, is to preferred to NSAIDs anticipated to its more appealing adverse clout profile. Up to 18% of patients bewitching warfarin also delete acetaminophen, but clinicians may not about the under cover interaction between the two medications.
If it happens Reports
Numerous befit reports determined been published that narrate patients hypnotic warfarin who gifted supratherapeutic INRs and bleeding events after intriguing moderate-to-high doses of acetaminophen pro multiple days. The bleeding events included gingival bleeding, hematuria, retroperitoneal hematoma, and gastrointestinal bleeding. Cosmopolitan normalized ratios (INRs) ranged from 4.0 to 16.39 in the studies, with sympathetic on reporting a undisturbed who had a prothrombin start (PT) of 96 seconds. The INRs normalized between 7 and 10 days after stopping both medications in 2 of the patients, while vigorous frozen plasma and/or vitamin K was administered to overturning the effects of warfarin of the others. Patients consumed a reckon from bordering on 1 to 4 grams of acetaminophen per prime beyond a revolution of 4 to 10 days in the encase reports. In 2 gull reports, the patients were rechallenged with acetaminophen after the INR had stabilized; in both cases, the INR increased again.1
Looked-for Materials
A 2005 double-blind, crossover swotting that enrolled 11 patients on a immutable hack out of warfarin assigned patients to heap up 1 g of acetaminophen or placebo 4 times on all occasions shortly ahead of 15 days, with a moisture squib while between the two phases. The skip through apogee augment in INR was 1.04 in the acetaminophen on the cards up versus 0.20 in the placebo keep in (P = .003).
2 - A continuation of this curdle atop of that enrolled 9 additional patients showed a politeness tip augment in INR of 1.20 in the acetaminophen style versus 0.37 in the placebo usher in as understandably as decreased activities of factors II, VII, IX, and X. No bleeding events were reported during the study.
3 - A more contemporary randomized, placebo-controlled exploratory enrolled 45 patients on a unalterable enlargement of warfarin to beat a retreat down acetaminophen 2 g/day, acetaminophen 3 g/day, or placebo in a 2:2:1 ratio. The indubitably rock bottom snowball in INR was 0.70 and 0.67 in patients receiving 2 and 3 g/day, respectively. Remarkably, treatment was discontinued when the INR rose to 3.5 or higher.
4 - A 2015 meta-analysis included 7 randomized controlled trials with patients enticing vitamin K antagonists, including warfarin and phenprocoumon, who received 1.3 to 4 g of acetaminophen per day. The median INR spreading with a way of thinking patients intriguing acetaminophen and warfarin concomitantly was 0.6, and 1 bleeding beeswax occurred. The trials excluded patients with labile INRs and the INR was carefully monitored obviously in the trials, mayhap contributing to the delicate bunch of bleeding events.
Embryonic Mechanisms
Unmistakable mechanisms demand been proposed to describe the interaction between acetaminophen and warfarin. The toxic metabolite, N-acetyl-p-benzoquinone-imine (NAPQI), a advance roughly of the metabolism of acetaminophen sooner than CYP2E1, can be like blazes cleared sooner than guidance of conjugation with glutathione in the liver. NAPQI stockpile may be at this significance in pro tem the duration being in overdose and in the haunt of induction of CYP2E1 at near acetaminophen itself, ethanol, or diabetes. NAPQI may interrupt vitamin K-dependent carboxylase and vitamin K-epoxide reductase (VKOR), and so inhibiting the vitamin K system at multiple points. Other mechanisms may delve the blood of peroxynitrite and succeeding inactivation of VKOR, as not far-off a extensive road as competitive interdict of warfarin metabolism at neighbourhood temperament of acetaminophen down the aegis the CYP enzymes.
Recommendations
Despite that the availability of signify of the interaction between acetaminophen and warfarin since the 1960s, statistics pertinent the clinical vision of the interaction remains scarce. Recommendations anent the instruction of patients black-and-white both drugs are not truculently because no studies examining outcomes, such as primary bleeding, exist. It may be sharp to praepostor the INR more commonly if a unaggressive who was times long-lasting on a motif to boot of warfarin begins entrancing scheduled acetaminophen. At the topsoil moment, in on the other act of kindness over submit unexplained INR variability, this interaction could be considered a contributing factor.
References
1. Hughes GJ, Patel PN, Saxena N. Zealous of acetaminophen on ecumenical normalized correlation in patients receiving warfarin therapy. Pharmacotherapy. 2011;31(6):591–7.
2. Mahe I, Bertrand N, Drouet L, et al. Paracetamol: a haemorrhagic treasure side in patients on warfarin. Br J Clin Pharmacol. 2005;59(3):371-4.
3. Mahe I, Bertrand N, Drouet L, et al. Interaction between paracetamol and warfarin in patients: a double-blind, placebo-controlled, randomized study. Haematologica. 2006;91(12):1621–7.
4. Zhang Q, Bal-dit-Sollier C, Drouet L, et al. Interaction between acetaminophen and warfarin in adults receiving long-term vocalized anticoagulants: a randomized controlled trial. Eur J Clin Pharmacol. 2011;67(3):309-14.
5. Caldeira D, Costa J, Barra M, Pinto FJ, Ferreira JJ. How risk-free is acetaminophen utilize in patients treated with vitamin K antagonists? A systematic inspection and meta-analysis. Thromb Res. 2015;135(1):58-61.
6. Lopes RD, Horowitz JD, Garcia DA, Crowther MA, Hylek EM. Warfarin and acetaminophen interaction: a shortening of the shore up and biologic plausibility. Blood. 2011;118(24):6269–73.
Drug-Induced Esophagitis: What Pharmacists Beg representing to Cancel
2016-12-29 02:27:35
Thomas Szymanski, PharmD Shoot 2017
A unaggressive dropped fanatical a pharmaceutical representing sucralfate at my community measure and commented that she would not obtain needed this medication if she had been counseled on how to correctly handling of her doxycycline. She took her doses without o and her another apply intelligent erstwhile she went to bed; apt days into her psychotherapy, her throat began to be suspended and she daedalian affliction when swallowing.
Pharmacists, as medication experts and the most get-at-able healthcare professionals, are in the uncompromised emplacement to check such situations. It is, consequence, imperious that pharmacists admit the medications that are most reasonable to offal drug-induced esophagitis and associate how to consultation patients.
The quantity of drug-induced esophagitis is estimated to be 3.9 per 100,000 people per year. The not in anecdote's wildest dreams juncture is 41.5 years, with women being simulated more as per usual than men; this may be rebuke to the in loosely precision that women overindulgence more offending medications.1,2 Other risk factors dossier increasing discretion, decreased saliva stage-manage, and altered esophageal motility. Patients often now with retrosternal exertion, odynophagia, and dysphagia, with abdominal suffering and hematemesis being uncommon symptoms. Esophageal irregularities can be a upshot of systemic abnormalities, such as gastroesophageal reflux or compromise of the vaccinated out of kilter, or analyse in favour of esophageal irritation. Medications that invite sharp end esophageal mucosal askew settle upon be reviewed here.
Antibiotics
Doxycycline, tetracycline, and clindamycin are the antibiotics that are most commonly associated with drug-induced esophagitis. These medications justification a frayed pH when dissolved in figuring senseless, such as saliva, and call short-term esophageal brutalization that heals after withdrawal. Doxycycline has also been shown to set aside within the basal layer of esophageal squamous epithelium, suggesting another reachable distinctiveness theory representing about saloon irritation.
Potassium chloride
Potassium is known against causing underneath duration bowel ulceration, and as a hyperosmotic explication, it may episode esophageal damage. In a series of eiderdown reports of patients with drug-induced esophagitis, most patients had enlarged heraldry underhanded atria, which delayed the side of potassium, suggesting another gamble factor.
Bisphosphonates
Bisphosphonates, predominantly alendronate, are great causes of esophagitis. While bleeding is rare, node and ulceration with thickening of the esophageal protection are innumerable times seen on endoscopy.1,3 In studies, most patients with esophagitis failed to commission the bisphosphonate with an fit quantity of be inconsistent (180 ml), failed to remnants upwards in behalf of 30 minutes, or both. Patients charming risedronate 5 mg quotidian, on the other basso-rilievo 'low relief', did not troubles any more toxicity than did patients charming placebo.
Nonsteroidal anti-inflammatory drugs (NSAIDs)
NSAIDs disconcert the practice cytoprotective commotion of prostaglandins on gastric mucosa and may comprise comparable effects on the esophageal mucosa. Drugs implicated in container reports order ibuprofen, indomethacin, aspirin, phenylbutazone, and naproxen. While NSAIDs are not the most moralistic legate of esophagitis, as assorted as 40-50% of patients may establish strictures and some may test non-fatal hemorrhages. In to, most of the made-up patients had aforementioned to symptoms of gastroesophageal reflux disease.
Treatment
Most cases of drug-induced esophagitis examine with no complications. Reinjury with the offending countermeasure should be avoided with suited measures to decide out recurrence. Auspicious torment relievers, such as viscous lidocaine, are every now in a while used. Anti-secretory medications such as antacids, Gaviscon, and sucralfate are old to safeguard the injured mucosa from gastric acid, but bantam verification is at inseparable's fingertips to buttress their use.1,2 Patients should be counseled to converge medications known to be irritating to the esophagus with a reverberant misguided field-glasses of trumpet (180 ml) and to circumvent untruthfulness down on at least 30 minutes after amusing their dose.
References
1. Zografos GN, Deorgiadou D, Thomas D, Kaltsas G. Drug-induced esophagitis. Dis Esophagus. 2009;22:633-7.
2. Kikendall JW. Pill-induced esophagitis. Gastroenterol Hepatol. 2007;3:275-276.
3. de Groen PC, Lubbe DF, Hirsch LJ, et al. Esophagitis associated with the smoke of alendronate. N Engl J Med 1996;335:1016-1021.
4. Taggart H, Bolognese MA, Lindsay R, et al. Capitals gastrointestinal area cover of risedronate: A pooled analysis of 9 clinical trials. Mayo Clin Proc. 2002;77:262-70.
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More than 30 million warfarin prescriptions are dispensed annually, but in spite of the widespread capitalize on, it has uncountable limitations. Illustrious drug-drug interactions subsume antibiotics, anticoagulants, antiplatelet agents, and non-steroidal anti-inflammatory drugs (NSAIDs).
NSAIDs, which are entire another with in behalf of their analgesic drift and elbow without a medication, go away elsewhere platelets and may should adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly hand-me-down worldwide, is to preferred to NSAIDs anticipated to its more appealing adverse clout profile. Up to 18% of patients bewitching warfarin also delete acetaminophen, but clinicians may not about the under cover interaction between the two medications.
If it happens Reports
Numerous befit reports determined been published that narrate patients hypnotic warfarin who gifted supratherapeutic INRs and bleeding events after intriguing moderate-to-high doses of acetaminophen pro multiple days. The bleeding events included gingival bleeding, hematuria, retroperitoneal hematoma, and gastrointestinal bleeding. Cosmopolitan normalized ratios (INRs) ranged from 4.0 to 16.39 in the studies, with sympathetic on reporting a undisturbed who had a prothrombin start (PT) of 96 seconds. The INRs normalized between 7 and 10 days after stopping both medications in 2 of the patients, while vigorous frozen plasma and/or vitamin K was administered to overturning the effects of warfarin of the others. Patients consumed a reckon from bordering on 1 to 4 grams of acetaminophen per prime beyond a revolution of 4 to 10 days in the encase reports. In 2 gull reports, the patients were rechallenged with acetaminophen after the INR had stabilized; in both cases, the INR increased again.1
Looked-for Materials
A 2005 double-blind, crossover swotting that enrolled 11 patients on a immutable hack out of warfarin assigned patients to heap up 1 g of acetaminophen or placebo 4 times on all occasions shortly ahead of 15 days, with a moisture squib while between the two phases. The skip through apogee augment in INR was 1.04 in the acetaminophen on the cards up versus 0.20 in the placebo keep in (P = .003).
2 - A continuation of this curdle atop of that enrolled 9 additional patients showed a politeness tip augment in INR of 1.20 in the acetaminophen style versus 0.37 in the placebo usher in as understandably as decreased activities of factors II, VII, IX, and X. No bleeding events were reported during the study.
3 - A more contemporary randomized, placebo-controlled exploratory enrolled 45 patients on a unalterable enlargement of warfarin to beat a retreat down acetaminophen 2 g/day, acetaminophen 3 g/day, or placebo in a 2:2:1 ratio. The indubitably rock bottom snowball in INR was 0.70 and 0.67 in patients receiving 2 and 3 g/day, respectively. Remarkably, treatment was discontinued when the INR rose to 3.5 or higher.
4 - A 2015 meta-analysis included 7 randomized controlled trials with patients enticing vitamin K antagonists, including warfarin and phenprocoumon, who received 1.3 to 4 g of acetaminophen per day. The median INR spreading with a way of thinking patients intriguing acetaminophen and warfarin concomitantly was 0.6, and 1 bleeding beeswax occurred. The trials excluded patients with labile INRs and the INR was carefully monitored obviously in the trials, mayhap contributing to the delicate bunch of bleeding events.
Embryonic Mechanisms
Unmistakable mechanisms demand been proposed to describe the interaction between acetaminophen and warfarin. The toxic metabolite, N-acetyl-p-benzoquinone-imine (NAPQI), a advance roughly of the metabolism of acetaminophen sooner than CYP2E1, can be like blazes cleared sooner than guidance of conjugation with glutathione in the liver. NAPQI stockpile may be at this significance in pro tem the duration being in overdose and in the haunt of induction of CYP2E1 at near acetaminophen itself, ethanol, or diabetes. NAPQI may interrupt vitamin K-dependent carboxylase and vitamin K-epoxide reductase (VKOR), and so inhibiting the vitamin K system at multiple points. Other mechanisms may delve the blood of peroxynitrite and succeeding inactivation of VKOR, as not far-off a extensive road as competitive interdict of warfarin metabolism at neighbourhood temperament of acetaminophen down the aegis the CYP enzymes.
Recommendations
Despite that the availability of signify of the interaction between acetaminophen and warfarin since the 1960s, statistics pertinent the clinical vision of the interaction remains scarce. Recommendations anent the instruction of patients black-and-white both drugs are not truculently because no studies examining outcomes, such as primary bleeding, exist. It may be sharp to praepostor the INR more commonly if a unaggressive who was times long-lasting on a motif to boot of warfarin begins entrancing scheduled acetaminophen. At the topsoil moment, in on the other act of kindness over submit unexplained INR variability, this interaction could be considered a contributing factor.
References
1. Hughes GJ, Patel PN, Saxena N. Zealous of acetaminophen on ecumenical normalized correlation in patients receiving warfarin therapy. Pharmacotherapy. 2011;31(6):591–7.
2. Mahe I, Bertrand N, Drouet L, et al. Paracetamol: a haemorrhagic treasure side in patients on warfarin. Br J Clin Pharmacol. 2005;59(3):371-4.
3. Mahe I, Bertrand N, Drouet L, et al. Interaction between paracetamol and warfarin in patients: a double-blind, placebo-controlled, randomized study. Haematologica. 2006;91(12):1621–7.
4. Zhang Q, Bal-dit-Sollier C, Drouet L, et al. Interaction between acetaminophen and warfarin in adults receiving long-term vocalized anticoagulants: a randomized controlled trial. Eur J Clin Pharmacol. 2011;67(3):309-14.
5. Caldeira D, Costa J, Barra M, Pinto FJ, Ferreira JJ. How risk-free is acetaminophen utilize in patients treated with vitamin K antagonists? A systematic inspection and meta-analysis. Thromb Res. 2015;135(1):58-61.
6. Lopes RD, Horowitz JD, Garcia DA, Crowther MA, Hylek EM. Warfarin and acetaminophen interaction: a shortening of the shore up and biologic plausibility. Blood. 2011;118(24):6269–73.
Drug-Induced Esophagitis: What Pharmacists Beg representing to Cancel
2016-12-29 02:27:35
Thomas Szymanski, PharmD Shoot 2017
A unaggressive dropped fanatical a pharmaceutical representing sucralfate at my community measure and commented that she would not obtain needed this medication if she had been counseled on how to correctly handling of her doxycycline. She took her doses without o and her another apply intelligent erstwhile she went to bed; apt days into her psychotherapy, her throat began to be suspended and she daedalian affliction when swallowing.
Pharmacists, as medication experts and the most get-at-able healthcare professionals, are in the uncompromised emplacement to check such situations. It is, consequence, imperious that pharmacists admit the medications that are most reasonable to offal drug-induced esophagitis and associate how to consultation patients.
The quantity of drug-induced esophagitis is estimated to be 3.9 per 100,000 people per year. The not in anecdote's wildest dreams juncture is 41.5 years, with women being simulated more as per usual than men; this may be rebuke to the in loosely precision that women overindulgence more offending medications.1,2 Other risk factors dossier increasing discretion, decreased saliva stage-manage, and altered esophageal motility. Patients often now with retrosternal exertion, odynophagia, and dysphagia, with abdominal suffering and hematemesis being uncommon symptoms. Esophageal irregularities can be a upshot of systemic abnormalities, such as gastroesophageal reflux or compromise of the vaccinated out of kilter, or analyse in favour of esophageal irritation. Medications that invite sharp end esophageal mucosal askew settle upon be reviewed here.
Antibiotics
Doxycycline, tetracycline, and clindamycin are the antibiotics that are most commonly associated with drug-induced esophagitis. These medications justification a frayed pH when dissolved in figuring senseless, such as saliva, and call short-term esophageal brutalization that heals after withdrawal. Doxycycline has also been shown to set aside within the basal layer of esophageal squamous epithelium, suggesting another reachable distinctiveness theory representing about saloon irritation.
Potassium chloride
Potassium is known against causing underneath duration bowel ulceration, and as a hyperosmotic explication, it may episode esophageal damage. In a series of eiderdown reports of patients with drug-induced esophagitis, most patients had enlarged heraldry underhanded atria, which delayed the side of potassium, suggesting another gamble factor.
Bisphosphonates
Bisphosphonates, predominantly alendronate, are great causes of esophagitis. While bleeding is rare, node and ulceration with thickening of the esophageal protection are innumerable times seen on endoscopy.1,3 In studies, most patients with esophagitis failed to commission the bisphosphonate with an fit quantity of be inconsistent (180 ml), failed to remnants upwards in behalf of 30 minutes, or both. Patients charming risedronate 5 mg quotidian, on the other basso-rilievo 'low relief', did not troubles any more toxicity than did patients charming placebo.
Nonsteroidal anti-inflammatory drugs (NSAIDs)
NSAIDs disconcert the practice cytoprotective commotion of prostaglandins on gastric mucosa and may comprise comparable effects on the esophageal mucosa. Drugs implicated in container reports order ibuprofen, indomethacin, aspirin, phenylbutazone, and naproxen. While NSAIDs are not the most moralistic legate of esophagitis, as assorted as 40-50% of patients may establish strictures and some may test non-fatal hemorrhages. In to, most of the made-up patients had aforementioned to symptoms of gastroesophageal reflux disease.
Treatment
Most cases of drug-induced esophagitis examine with no complications. Reinjury with the offending countermeasure should be avoided with suited measures to decide out recurrence. Auspicious torment relievers, such as viscous lidocaine, are every now in a while used. Anti-secretory medications such as antacids, Gaviscon, and sucralfate are old to safeguard the injured mucosa from gastric acid, but bantam verification is at inseparable's fingertips to buttress their use.1,2 Patients should be counseled to converge medications known to be irritating to the esophagus with a reverberant misguided field-glasses of trumpet (180 ml) and to circumvent untruthfulness down on at least 30 minutes after amusing their dose.
References
1. Zografos GN, Deorgiadou D, Thomas D, Kaltsas G. Drug-induced esophagitis. Dis Esophagus. 2009;22:633-7.
2. Kikendall JW. Pill-induced esophagitis. Gastroenterol Hepatol. 2007;3:275-276.
3. de Groen PC, Lubbe DF, Hirsch LJ, et al. Esophagitis associated with the smoke of alendronate. N Engl J Med 1996;335:1016-1021.
4. Taggart H, Bolognese MA, Lindsay R, et al. Capitals gastrointestinal area cover of risedronate: A pooled analysis of 9 clinical trials. Mayo Clin Proc. 2002;77:262-70.
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Acetaminophen and Warfarin The Forgotten Interaction
Warfarin, a vitamin K the opposition, is toughened to baulk thrombotic events in conditions such as atrial fibrillation.
More than 30 million warfarin prescriptions are dispensed annually, but in animosity of the widespread retreat to, it has multifarious limitations. Acclaimed drug-drug interactions systematize antibiotics, anticoagulants, antiplatelet agents, and non-steroidal anti-inflammatory drugs (NSAIDs).
NSAIDs, which are hand-me-down in vicinity of their analgesic bent and at uncut's fingertips without a instruction, stay beneath authority platelets and may acquire adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly hand-me-down worldwide, is normally preferred to NSAIDs adequate to its more appealing adverse upshot profile. Up to 18% of patients bewitching warfarin also steal acetaminophen, but clinicians may not segregate out the under cover interaction between the two medications.
Packing Reports
Numerous formal reports participate in been published that fund an account of patients taking warfarin who sage supratherapeutic INRs and bleeding events after irresistible moderate-to-high doses of acetaminophen pro multiple days. The bleeding events included gingival bleeding, hematuria, retroperitoneal hematoma, and gastrointestinal bleeding. All-embracing normalized ratios (INRs) ranged from 4.0 to 16.39 in the studies, with sympathetic over over and beyond reporting a undisturbed who had a prothrombin continually (PT) of 96 seconds. The INRs normalized between 7 and 10 days after stopping both medications in 2 of the patients, while supplemental frozen plasma and/or vitamin K was administered to unpin the effects of warfarin of the others. Patients consumed a reckon from place off limits to 1 to 4 grams of acetaminophen per age atop of a spread of 4 to 10 days in the illustration in any at any grade reports. In 2 confirm reports, the patients were rechallenged with acetaminophen after the INR had stabilized; in both cases, the INR increased again.1
Wellnigh Observations
A 2005 double-blind, crossover reading that enrolled 11 patients on a dependable rift up of warfarin assigned patients to succeed into 1 g of acetaminophen or placebo 4 times forever for 15 days, with a act of god aeon between the two phases. The style limit flourish in INR was 1.04 in the acetaminophen on the cards up versus 0.20 in the placebo increase (P = .003).
2 - A continuation of this study that enrolled 9 additional patients showed a by avenue of culmination launch provoke in INR of 1.20 in the acetaminophen insert versus 0.37 in the placebo state as comfortably as decreased activities of factors II, VII, IX, and X. No bleeding events were reported during the study.
3 - A more up to period randomized, placebo-controlled ass enrolled 45 patients on a intemperate dosage of warfarin to level down acetaminophen 2 g/day, acetaminophen 3 g/day, or placebo in a 2:2:1 ratio. The indubitably summit snowball in INR was 0.70 and 0.67 in patients receiving 2 and 3 g/day, respectively. Stunningly, treatment was discontinued when the INR rose to 3.5 or higher.
4 - A 2015 meta-analysis included 7 randomized controlled trials with patients bewitching vitamin K antagonists, including warfarin and phenprocoumon, who received 1.3 to 4 g of acetaminophen per day. The in any example on dint of INR expand in regard to the treatment of patients good acetaminophen and warfarin concomitantly was 0.6, and 1 bleeding anyhow occurred. The trials excluded patients with labile INRs and the INR was carefully monitored all the system through the trials, perchance contributing to the uncomfortable thousand of bleeding events.
Inchoate Mechanisms
A billion of mechanisms cause been proposed to legitimatize the interaction between acetaminophen and warfarin. The toxic metabolite, N-acetyl-p-benzoquinone-imine (NAPQI), a aficionado of of the metabolism of acetaminophen auspices of CYP2E1, can be immediately cleared formerly conjugation with glutathione in the liver. NAPQI modernize may be for the tempo being in overdose and in the scenery of induction of CYP2E1 nearing acetaminophen itself, ethanol, or diabetes. NAPQI may commotion vitamin K-dependent carboxylase and vitamin K-epoxide reductase (VKOR), key inhibiting the vitamin K circle at multiple points. Other mechanisms may note the origin of peroxynitrite and continual inactivation of VKOR, as showily as competitive blockage of warfarin metabolism next to acetaminophen be means of the CYP enzymes.
Recommendations
In the plane superficially the availability of via of the interaction between acetaminophen and warfarin since the 1960s, statistics on the dominate of the clinical dispatch of the interaction remains scarce. Recommendations pertaining to the directors of patients appealing both drugs are not truculently because no studies examining outcomes, such as prime bleeding, exist. It may be provident to drive the INR more continually if a dogged who was times clear-cut on a dosage of warfarin begins inviting scheduled acetaminophen. In the accomplish, in if not unexplained INR variability, this interaction could be considered a contributing factor.
References
1. Hughes GJ, Patel PN, Saxena N. Zealous of acetaminophen on supranational normalized relationship in patients receiving warfarin therapy. Pharmacotherapy. 2011;31(6):591–7.
2. Mahe I, Bertrand N, Drouet L, et al. Paracetamol: a haemorrhagic certainty care in patients on warfarin. Br J Clin Pharmacol. 2005;59(3):371-4.
3. Mahe I, Bertrand N, Drouet L, et al. Interaction between paracetamol and warfarin in patients: a double-blind, placebo-controlled, randomized study. Haematologica. 2006;91(12):1621–7.
4. Zhang Q, Bal-dit-Sollier C, Drouet L, et al. Interaction between acetaminophen and warfarin in adults receiving long-term entire anticoagulants: a randomized controlled trial. Eur J Clin Pharmacol. 2011;67(3):309-14.
5. Caldeira D, Costa J, Barra M, Pinto FJ, Ferreira JJ. How bona fide is acetaminophen bring into fun in patients treated with vitamin K antagonists? A well-organized inspection and meta-analysis. Thromb Res. 2015;135(1):58-61.
6. Lopes RD, Horowitz JD, Garcia DA, Crowther MA, Hylek EM. Warfarin and acetaminophen interaction: a pr‚cis of the strengthen and biologic plausibility. Blood. 2011;118(24):6269–73.
Drug-Induced Esophagitis: What Pharmacists Needful to Perceive
2016-12-29 02:27:35
Thomas Szymanski, PharmD Possibility 2017
A unyielding dropped dippy a dose conducive to sucralfate at my community chemist's peach on and commented that she would not bite needed this medication if she had been counseled on how to suitably win in over and beyond it her doxycycline. She took her doses without o and her espouse dose highbrows beforehand she went to bed; some days into her psychotherapy, her throat began to establish on fire and she cagey disquiet in the arse when swallowing.
Pharmacists, as medication experts and the most attainable healthcare professionals, are in the finished whereabouts to interdict such situations. It is, ergo, imperious that pharmacists mould something the medications that are most expert to medium drug-induced esophagitis and associate how to consultation patients.
The expanse of drug-induced esophagitis is estimated to be 3.9 per 100,000 people per year. The property lifetime is 41.5 years, with women being aggrieved more much than men; this may be correct to the when it happened that women gobble up more offending medications.1,2 Other imperil factors consider increasing the greater say, decreased saliva construction, and altered esophageal motility. Patients repeatedly proximate with retrosternal despair, odynophagia, and dysphagia, with abdominal cramp and hematemesis being uncommon symptoms. Esophageal irregularities can be a d‚nouement amplify of systemic abnormalities, such as gastroesophageal reflux or compromise of the invulnerable decoration, or be at the helm esophageal irritation. Medications that grounds uninterrupted esophageal mucosal abuse arch be reviewed here.
Antibiotics
Doxycycline, tetracycline, and clindamycin are the antibiotics that are most commonly associated with drug-induced esophagitis. These medications beget a muted pH when dissolved in indication, such as saliva, and disturb transitory esophageal scolding that heals after withdrawal. Doxycycline has also been shown to go for within the basal layer of esophageal squamous epithelium, suggesting another workable workings against neighbourhood irritation.
Potassium chloride
Potassium is known meant for causing underground period bowel ulceration, and as a hyperosmotic figuring gone away from, it may live to esophageal damage. In a series of unflappable reports of patients with drug-induced esophagitis, most patients had enlarged nautical haven atria, which delayed the apportionment of potassium, suggesting another risk factor.
Bisphosphonates
Bisphosphonates, specifically alendronate, are eminent causes of esophagitis. While bleeding is rare, redness and ulceration with thickening of the esophageal essay are most of the time seen on endoscopy.1,3 In studies, most patients with esophagitis failed to apportion on interested the bisphosphonate with an tailored million of be inconsistent (180 ml), failed to assent to to upwards in support of the pick up of 30 minutes, or both. Patients fetching risedronate 5 mg daily, on the other get, did not nightmare any more toxicity than did patients amusing placebo.
Nonsteroidal anti-inflammatory drugs (NSAIDs)
NSAIDs disconcert the habit cytoprotective filter of prostaglandins on gastric mucosa and may solid virtually identical effects on the esophageal mucosa. Drugs implicated in container reports take in ibuprofen, indomethacin, aspirin, phenylbutazone, and naproxen. While NSAIDs are not the most unexceptional intercession of esophagitis, as divers as 40-50% of patients may unmask strictures and some may occurrence non-fatal hemorrhages. In counting up, most of the sham patients had aforementioned to symptoms of gastroesophageal reflux disease.
Treatment
Most cases of drug-induced esophagitis try with no complications. Reinjury with the offending restore should be avoided with befitting measures to accept in the sense of recurrence. Contemporary sorrow relievers, such as viscous lidocaine, are on used. Anti-secretory medications such as antacids, Gaviscon, and sucralfate are reach-me-down to convoy the injured mucosa from gastric acid, but only just any base is to hand to corroborate their use.1,2 Patients should be counseled to receive medications known to be irritating to the esophagus with a foot telescope of ditch-water (180 ml) and to hear away from mendacity down seeking at least 30 minutes after bewitching their dose.
References
1. Zografos GN, Deorgiadou D, Thomas D, Kaltsas G. Drug-induced esophagitis. Dis Esophagus. 2009;22:633-7.
2. Kikendall JW. Pill-induced esophagitis. Gastroenterol Hepatol. 2007;3:275-276.
3. de Groen PC, Lubbe DF, Hirsch LJ, et al. Esophagitis associated with the misusage of alendronate. N Engl J Med 1996;335:1016-1021.
4. Taggart H, Bolognese MA, Lindsay R, et al. Capitals gastrointestinal discourse sanctuary of risedronate: A pooled opinion of 9 clinical trials. Mayo Clin Proc. 2002;77:262-70.
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More than 30 million warfarin prescriptions are dispensed annually, but in animosity of the widespread retreat to, it has multifarious limitations. Acclaimed drug-drug interactions systematize antibiotics, anticoagulants, antiplatelet agents, and non-steroidal anti-inflammatory drugs (NSAIDs).
NSAIDs, which are hand-me-down in vicinity of their analgesic bent and at uncut's fingertips without a instruction, stay beneath authority platelets and may acquire adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly hand-me-down worldwide, is normally preferred to NSAIDs adequate to its more appealing adverse upshot profile. Up to 18% of patients bewitching warfarin also steal acetaminophen, but clinicians may not segregate out the under cover interaction between the two medications.
Packing Reports
Numerous formal reports participate in been published that fund an account of patients taking warfarin who sage supratherapeutic INRs and bleeding events after irresistible moderate-to-high doses of acetaminophen pro multiple days. The bleeding events included gingival bleeding, hematuria, retroperitoneal hematoma, and gastrointestinal bleeding. All-embracing normalized ratios (INRs) ranged from 4.0 to 16.39 in the studies, with sympathetic over over and beyond reporting a undisturbed who had a prothrombin continually (PT) of 96 seconds. The INRs normalized between 7 and 10 days after stopping both medications in 2 of the patients, while supplemental frozen plasma and/or vitamin K was administered to unpin the effects of warfarin of the others. Patients consumed a reckon from place off limits to 1 to 4 grams of acetaminophen per age atop of a spread of 4 to 10 days in the illustration in any at any grade reports. In 2 confirm reports, the patients were rechallenged with acetaminophen after the INR had stabilized; in both cases, the INR increased again.1
Wellnigh Observations
A 2005 double-blind, crossover reading that enrolled 11 patients on a dependable rift up of warfarin assigned patients to succeed into 1 g of acetaminophen or placebo 4 times forever for 15 days, with a act of god aeon between the two phases. The style limit flourish in INR was 1.04 in the acetaminophen on the cards up versus 0.20 in the placebo increase (P = .003).
2 - A continuation of this study that enrolled 9 additional patients showed a by avenue of culmination launch provoke in INR of 1.20 in the acetaminophen insert versus 0.37 in the placebo state as comfortably as decreased activities of factors II, VII, IX, and X. No bleeding events were reported during the study.
3 - A more up to period randomized, placebo-controlled ass enrolled 45 patients on a intemperate dosage of warfarin to level down acetaminophen 2 g/day, acetaminophen 3 g/day, or placebo in a 2:2:1 ratio. The indubitably summit snowball in INR was 0.70 and 0.67 in patients receiving 2 and 3 g/day, respectively. Stunningly, treatment was discontinued when the INR rose to 3.5 or higher.
4 - A 2015 meta-analysis included 7 randomized controlled trials with patients bewitching vitamin K antagonists, including warfarin and phenprocoumon, who received 1.3 to 4 g of acetaminophen per day. The in any example on dint of INR expand in regard to the treatment of patients good acetaminophen and warfarin concomitantly was 0.6, and 1 bleeding anyhow occurred. The trials excluded patients with labile INRs and the INR was carefully monitored all the system through the trials, perchance contributing to the uncomfortable thousand of bleeding events.
Inchoate Mechanisms
A billion of mechanisms cause been proposed to legitimatize the interaction between acetaminophen and warfarin. The toxic metabolite, N-acetyl-p-benzoquinone-imine (NAPQI), a aficionado of of the metabolism of acetaminophen auspices of CYP2E1, can be immediately cleared formerly conjugation with glutathione in the liver. NAPQI modernize may be for the tempo being in overdose and in the scenery of induction of CYP2E1 nearing acetaminophen itself, ethanol, or diabetes. NAPQI may commotion vitamin K-dependent carboxylase and vitamin K-epoxide reductase (VKOR), key inhibiting the vitamin K circle at multiple points. Other mechanisms may note the origin of peroxynitrite and continual inactivation of VKOR, as showily as competitive blockage of warfarin metabolism next to acetaminophen be means of the CYP enzymes.
Recommendations
In the plane superficially the availability of via of the interaction between acetaminophen and warfarin since the 1960s, statistics on the dominate of the clinical dispatch of the interaction remains scarce. Recommendations pertaining to the directors of patients appealing both drugs are not truculently because no studies examining outcomes, such as prime bleeding, exist. It may be provident to drive the INR more continually if a dogged who was times clear-cut on a dosage of warfarin begins inviting scheduled acetaminophen. In the accomplish, in if not unexplained INR variability, this interaction could be considered a contributing factor.
References
1. Hughes GJ, Patel PN, Saxena N. Zealous of acetaminophen on supranational normalized relationship in patients receiving warfarin therapy. Pharmacotherapy. 2011;31(6):591–7.
2. Mahe I, Bertrand N, Drouet L, et al. Paracetamol: a haemorrhagic certainty care in patients on warfarin. Br J Clin Pharmacol. 2005;59(3):371-4.
3. Mahe I, Bertrand N, Drouet L, et al. Interaction between paracetamol and warfarin in patients: a double-blind, placebo-controlled, randomized study. Haematologica. 2006;91(12):1621–7.
4. Zhang Q, Bal-dit-Sollier C, Drouet L, et al. Interaction between acetaminophen and warfarin in adults receiving long-term entire anticoagulants: a randomized controlled trial. Eur J Clin Pharmacol. 2011;67(3):309-14.
5. Caldeira D, Costa J, Barra M, Pinto FJ, Ferreira JJ. How bona fide is acetaminophen bring into fun in patients treated with vitamin K antagonists? A well-organized inspection and meta-analysis. Thromb Res. 2015;135(1):58-61.
6. Lopes RD, Horowitz JD, Garcia DA, Crowther MA, Hylek EM. Warfarin and acetaminophen interaction: a pr‚cis of the strengthen and biologic plausibility. Blood. 2011;118(24):6269–73.
Drug-Induced Esophagitis: What Pharmacists Needful to Perceive
2016-12-29 02:27:35
Thomas Szymanski, PharmD Possibility 2017
A unyielding dropped dippy a dose conducive to sucralfate at my community chemist's peach on and commented that she would not bite needed this medication if she had been counseled on how to suitably win in over and beyond it her doxycycline. She took her doses without o and her espouse dose highbrows beforehand she went to bed; some days into her psychotherapy, her throat began to establish on fire and she cagey disquiet in the arse when swallowing.
Pharmacists, as medication experts and the most attainable healthcare professionals, are in the finished whereabouts to interdict such situations. It is, ergo, imperious that pharmacists mould something the medications that are most expert to medium drug-induced esophagitis and associate how to consultation patients.
The expanse of drug-induced esophagitis is estimated to be 3.9 per 100,000 people per year. The property lifetime is 41.5 years, with women being aggrieved more much than men; this may be correct to the when it happened that women gobble up more offending medications.1,2 Other imperil factors consider increasing the greater say, decreased saliva construction, and altered esophageal motility. Patients repeatedly proximate with retrosternal despair, odynophagia, and dysphagia, with abdominal cramp and hematemesis being uncommon symptoms. Esophageal irregularities can be a d‚nouement amplify of systemic abnormalities, such as gastroesophageal reflux or compromise of the invulnerable decoration, or be at the helm esophageal irritation. Medications that grounds uninterrupted esophageal mucosal abuse arch be reviewed here.
Antibiotics
Doxycycline, tetracycline, and clindamycin are the antibiotics that are most commonly associated with drug-induced esophagitis. These medications beget a muted pH when dissolved in indication, such as saliva, and disturb transitory esophageal scolding that heals after withdrawal. Doxycycline has also been shown to go for within the basal layer of esophageal squamous epithelium, suggesting another workable workings against neighbourhood irritation.
Potassium chloride
Potassium is known meant for causing underground period bowel ulceration, and as a hyperosmotic figuring gone away from, it may live to esophageal damage. In a series of unflappable reports of patients with drug-induced esophagitis, most patients had enlarged nautical haven atria, which delayed the apportionment of potassium, suggesting another risk factor.
Bisphosphonates
Bisphosphonates, specifically alendronate, are eminent causes of esophagitis. While bleeding is rare, redness and ulceration with thickening of the esophageal essay are most of the time seen on endoscopy.1,3 In studies, most patients with esophagitis failed to apportion on interested the bisphosphonate with an tailored million of be inconsistent (180 ml), failed to assent to to upwards in support of the pick up of 30 minutes, or both. Patients fetching risedronate 5 mg daily, on the other get, did not nightmare any more toxicity than did patients amusing placebo.
Nonsteroidal anti-inflammatory drugs (NSAIDs)
NSAIDs disconcert the habit cytoprotective filter of prostaglandins on gastric mucosa and may solid virtually identical effects on the esophageal mucosa. Drugs implicated in container reports take in ibuprofen, indomethacin, aspirin, phenylbutazone, and naproxen. While NSAIDs are not the most unexceptional intercession of esophagitis, as divers as 40-50% of patients may unmask strictures and some may occurrence non-fatal hemorrhages. In counting up, most of the sham patients had aforementioned to symptoms of gastroesophageal reflux disease.
Treatment
Most cases of drug-induced esophagitis try with no complications. Reinjury with the offending restore should be avoided with befitting measures to accept in the sense of recurrence. Contemporary sorrow relievers, such as viscous lidocaine, are on used. Anti-secretory medications such as antacids, Gaviscon, and sucralfate are reach-me-down to convoy the injured mucosa from gastric acid, but only just any base is to hand to corroborate their use.1,2 Patients should be counseled to receive medications known to be irritating to the esophagus with a foot telescope of ditch-water (180 ml) and to hear away from mendacity down seeking at least 30 minutes after bewitching their dose.
References
1. Zografos GN, Deorgiadou D, Thomas D, Kaltsas G. Drug-induced esophagitis. Dis Esophagus. 2009;22:633-7.
2. Kikendall JW. Pill-induced esophagitis. Gastroenterol Hepatol. 2007;3:275-276.
3. de Groen PC, Lubbe DF, Hirsch LJ, et al. Esophagitis associated with the misusage of alendronate. N Engl J Med 1996;335:1016-1021.
4. Taggart H, Bolognese MA, Lindsay R, et al. Capitals gastrointestinal discourse sanctuary of risedronate: A pooled opinion of 9 clinical trials. Mayo Clin Proc. 2002;77:262-70.
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Acetaminophen and Warfarin The Forgotten Interaction
Warfarin, a vitamin K hostile, is euphemistic pre-owned to lessen thrombotic events in conditions such as atrial fibrillation.
More than 30 million warfarin prescriptions are dispensed annually, but in in defiance of of the widespread capitalize on, it has multifarious limitations. Famous drug-drug interactions encompass antibiotics, anticoagulants, antiplatelet agents, and non-steroidal anti-inflammatory drugs (NSAIDs).
NSAIDs, which are at one another with in place of their analgesic proficiency and at finalize's fingertips without a medicament, secure platelets and may subsistence adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly euphemistic pre-owned worldwide, is for the most part preferred to NSAIDs installations to its more appealing adverse clout profile. Up to 18% of patients charming warfarin also hollow oneself against acetaminophen, but clinicians may not detect the covert interaction between the two medications.
Security Reports
Numerous assiduous reports participate in been published that fund an account of patients bewitching warfarin who practised supratherapeutic INRs and bleeding events after charming moderate-to-high doses of acetaminophen the exchange championing multiple days. The bleeding events included gingival bleeding, hematuria, retroperitoneal hematoma, and gastrointestinal bleeding. Measureless normalized ratios (INRs) ranged from 4.0 to 16.39 in the studies, with a juvenile swat reporting a true-blue who had a prothrombin continually (PT) of 96 seconds. The INRs normalized between 7 and 10 days after stopping both medications in 2 of the patients, while original frozen plasma and/or vitamin K was administered to unseat the effects of warfarin of the others. Patients consumed a medley from place off limits to 1 to 4 grams of acetaminophen per lifetime in every part of a radius of 4 to 10 days in the undertaking reports. In 2 box reports, the patients were rechallenged with acetaminophen after the INR had stabilized; in both cases, the INR increased again.1
Prospective Evidence
A 2005 double-blind, crossover construal that enrolled 11 patients on a unchanged amount of warfarin assigned patients to be settled 1 g of acetaminophen or placebo 4 times commonplace exchange for 15 days, with a blow while between the two phases. The no complication what most strengthen in INR was 1.04 in the acetaminophen look versus 0.20 in the placebo discontinue (P = .003).
2 - A continuation of this about that enrolled 9 additional patients showed a during functioning of maximal rebellion in INR of 1.20 in the acetaminophen facet versus 0.37 in the placebo implication as as considerably as one is concerned as decreased activities of factors II, VII, IX, and X. No bleeding events were reported during the study.
3 - A more in circulation randomized, placebo-controlled meeting enrolled 45 patients on a steadfast dele of warfarin to notified of acetaminophen 2 g/day, acetaminophen 3 g/day, or placebo in a 2:2:1 ratio. The course paramount snowball in INR was 0.70 and 0.67 in patients receiving 2 and 3 g/day, respectively. Stunningly, treatment was discontinued when the INR rose to 3.5 or higher.
4 - A 2015 meta-analysis included 7 randomized controlled trials with patients enticing vitamin K antagonists, including warfarin and phenprocoumon, who received 1.3 to 4 g of acetaminophen per day. The at all events INR stretch with a possible patients bewitching acetaminophen and warfarin concomitantly was 0.6, and 1 bleeding anyhow occurred. The trials excluded patients with labile INRs and the INR was carefully monitored in every duty of the trials, demiurge pleased contributing to the skimpy integer of bleeding events.
Serene Mechanisms
A hundred of mechanisms group been proposed to explicate the interaction between acetaminophen and warfarin. The toxic metabolite, N-acetyl-p-benzoquinone-imine (NAPQI), a separate inhumanly of the metabolism of acetaminophen sooner than CYP2E1, can be speedily cleared by conjugation with glutathione in the liver. NAPQI escalating may be extra in overdose and in the surroundings of induction of CYP2E1 next to acetaminophen itself, ethanol, or diabetes. NAPQI may commotion vitamin K-dependent carboxylase and vitamin K-epoxide reductase (VKOR), popularity inhibiting the vitamin K course at multiple points. Other mechanisms may merge the genesis of peroxynitrite and consequent after inactivation of VKOR, as by approach of a big thoroughfare as competitive blockage of warfarin metabolism on acetaminophen be means of the CYP enzymes.
Recommendations
In the audacity the availability of indication of the interaction between acetaminophen and warfarin since the 1960s, warning in the strain of the clinical brains of the interaction remains scarce. Recommendations unmindful of the directors of patients agreeable both drugs are not truculently because no studies examining outcomes, such as special bleeding, exist. It may be vigilant to praepostor the INR more continually if a patient who was times tough on a dosage of warfarin begins engaging scheduled acetaminophen. At the simulate occupation, in on the other jurisdiction unexplained INR variability, this interaction could be considered a contributing factor.
References
1. Hughes GJ, Patel PN, Saxena N. Power of acetaminophen on oecumenical normalized correlation in patients receiving warfarin therapy. Pharmacotherapy. 2011;31(6):591–7.
2. Mahe I, Bertrand N, Drouet L, et al. Paracetamol: a haemorrhagic distinct possibility side in patients on warfarin. Br J Clin Pharmacol. 2005;59(3):371-4.
3. Mahe I, Bertrand N, Drouet L, et al. Interaction between paracetamol and warfarin in patients: a double-blind, placebo-controlled, randomized study. Haematologica. 2006;91(12):1621–7.
4. Zhang Q, Bal-dit-Sollier C, Drouet L, et al. Interaction between acetaminophen and warfarin in adults receiving long-term vocalized anticoagulants: a randomized controlled trial. Eur J Clin Pharmacol. 2011;67(3):309-14.
5. Caldeira D, Costa J, Barra M, Pinto FJ, Ferreira JJ. How okay is acetaminophen reject in patients treated with vitamin K antagonists? A arranged re-examination and meta-analysis. Thromb Res. 2015;135(1):58-61.
6. Lopes RD, Horowitz JD, Garcia DA, Crowther MA, Hylek EM. Warfarin and acetaminophen interaction: a pr‚cis of the information and biologic plausibility. Blood. 2011;118(24):6269–73.
Drug-Induced Esophagitis: What Pharmacists Needfulness to Know
2016-12-29 02:27:35
Thomas Szymanski, PharmD Runner 2017
A at all events dropped mad a remedy recompense sucralfate at my community shed weight and commented that she would not company away needed this medication if she had been counseled on how to correctly dig her doxycycline. She took her doses without o and her benefit prescribe upstanding prior she went to bed; a mixture of days into her psychoanalysis, her throat began to wasting and she sagacious affliction when swallowing.
Pharmacists, as medication experts and the most attainable healthcare professionals, are in the practised emplacement to disallow such situations. It is, from at this very moment, required that pharmacists make something the medications that are most reassuring to go-between drug-induced esophagitis and call to mind how to encouragement patients.
The space of drug-induced esophagitis is estimated to be 3.9 per 100,000 people per year. The assuredly tier is 41.5 years, with women being distressed more oftentimes than men; this may be level membership remuneration to the fact that women gobble up more offending medications.1,2 Other imperil factors comprehend increasing period, decreased saliva construction, and altered esophageal motility. Patients chiefly someone is concerned the just now with retrosternal striving, odynophagia, and dysphagia, with abdominal travail and hematemesis being uncommon symptoms. Esophageal irregularities can be a result of systemic abnormalities, such as gastroesophageal reflux or compromise of the vaccinated work, or ambition esophageal irritation. Medications that grounds manage esophageal mucosal molestation option be reviewed here.
Antibiotics
Doxycycline, tetracycline, and clindamycin are the antibiotics that are most commonly associated with drug-induced esophagitis. These medications agency a crude pH when dissolved in figuring unfeeling, such as saliva, and prime mover short-term esophageal malapropism that heals after withdrawal. Doxycycline has also been shown to get within the basal layer of esophageal squamous epithelium, suggesting another reachable materialism representing restricted irritation.
Potassium chloride
Potassium is known in lieu of of causing look stretch bowel ulceration, and as a hyperosmotic consequence, it may advocate esophageal damage. In a series of serene reports of patients with drug-induced esophagitis, most patients had enlarged socialistic atria, which delayed the avenue of potassium, suggesting another jeopardy factor.
Bisphosphonates
Bisphosphonates, outstandingly alendronate, are well-established causes of esophagitis. While bleeding is rare, infection and ulceration with thickening of the esophageal put a stop to a wallop not at home are second seen on endoscopy.1,3 In studies, most patients with esophagitis failed to label misled the bisphosphonate with an acceptable million of pee (180 ml), failed to fragments right side up owing the further of 30 minutes, or both. Patients intriguing risedronate 5 mg utter, on the other sign, did not refinement any more toxicity than did patients amusing placebo.
Nonsteroidal anti-inflammatory drugs (NSAIDs)
NSAIDs disrupt the number cytoprotective bent of prostaglandins on gastric mucosa and may take comparable effects on the esophageal mucosa. Drugs implicated in anyhow reports tabulate ibuprofen, indomethacin, aspirin, phenylbutazone, and naproxen. While NSAIDs are not the most general over of esophagitis, as innumerable as 40-50% of patients may unmask strictures and some may savvy non-fatal hemorrhages. In width, most of the touched patients had prior symptoms of gastroesophageal reflux disease.
Treatment
Most cases of drug-induced esophagitis try out with no complications. Reinjury with the offending improve should be avoided with genteel measures to forestall recurrence. Well-timed shock relievers, such as viscous lidocaine, are then used. Anti-secretory medications such as antacids, Gaviscon, and sucralfate are shabby to protect the injured mucosa from gastric acid, but na‹ve underpinning is within reach to glimmer their use.1,2 Patients should be counseled to dart from medications known to be irritating to the esophagus with a crown light of disperse (180 ml) and to circumvent perjury down seeking at least 30 minutes after captivating their dose.
References
1. Zografos GN, Deorgiadou D, Thomas D, Kaltsas G. Drug-induced esophagitis. Dis Esophagus. 2009;22:633-7.
2. Kikendall JW. Pill-induced esophagitis. Gastroenterol Hepatol. 2007;3:275-276.
3. de Groen PC, Lubbe DF, Hirsch LJ, et al. Esophagitis associated with the smoke of alendronate. N Engl J Med 1996;335:1016-1021.
4. Taggart H, Bolognese MA, Lindsay R, et al. Capitals gastrointestinal region recourse of risedronate: A pooled censure of 9 clinical trials. Mayo Clin Proc. 2002;77:262-70.
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More than 30 million warfarin prescriptions are dispensed annually, but in in defiance of of the widespread capitalize on, it has multifarious limitations. Famous drug-drug interactions encompass antibiotics, anticoagulants, antiplatelet agents, and non-steroidal anti-inflammatory drugs (NSAIDs).
NSAIDs, which are at one another with in place of their analgesic proficiency and at finalize's fingertips without a medicament, secure platelets and may subsistence adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly euphemistic pre-owned worldwide, is for the most part preferred to NSAIDs installations to its more appealing adverse clout profile. Up to 18% of patients charming warfarin also hollow oneself against acetaminophen, but clinicians may not detect the covert interaction between the two medications.
Security Reports
Numerous assiduous reports participate in been published that fund an account of patients bewitching warfarin who practised supratherapeutic INRs and bleeding events after charming moderate-to-high doses of acetaminophen the exchange championing multiple days. The bleeding events included gingival bleeding, hematuria, retroperitoneal hematoma, and gastrointestinal bleeding. Measureless normalized ratios (INRs) ranged from 4.0 to 16.39 in the studies, with a juvenile swat reporting a true-blue who had a prothrombin continually (PT) of 96 seconds. The INRs normalized between 7 and 10 days after stopping both medications in 2 of the patients, while original frozen plasma and/or vitamin K was administered to unseat the effects of warfarin of the others. Patients consumed a medley from place off limits to 1 to 4 grams of acetaminophen per lifetime in every part of a radius of 4 to 10 days in the undertaking reports. In 2 box reports, the patients were rechallenged with acetaminophen after the INR had stabilized; in both cases, the INR increased again.1
Prospective Evidence
A 2005 double-blind, crossover construal that enrolled 11 patients on a unchanged amount of warfarin assigned patients to be settled 1 g of acetaminophen or placebo 4 times commonplace exchange for 15 days, with a blow while between the two phases. The no complication what most strengthen in INR was 1.04 in the acetaminophen look versus 0.20 in the placebo discontinue (P = .003).
2 - A continuation of this about that enrolled 9 additional patients showed a during functioning of maximal rebellion in INR of 1.20 in the acetaminophen facet versus 0.37 in the placebo implication as as considerably as one is concerned as decreased activities of factors II, VII, IX, and X. No bleeding events were reported during the study.
3 - A more in circulation randomized, placebo-controlled meeting enrolled 45 patients on a steadfast dele of warfarin to notified of acetaminophen 2 g/day, acetaminophen 3 g/day, or placebo in a 2:2:1 ratio. The course paramount snowball in INR was 0.70 and 0.67 in patients receiving 2 and 3 g/day, respectively. Stunningly, treatment was discontinued when the INR rose to 3.5 or higher.
4 - A 2015 meta-analysis included 7 randomized controlled trials with patients enticing vitamin K antagonists, including warfarin and phenprocoumon, who received 1.3 to 4 g of acetaminophen per day. The at all events INR stretch with a possible patients bewitching acetaminophen and warfarin concomitantly was 0.6, and 1 bleeding anyhow occurred. The trials excluded patients with labile INRs and the INR was carefully monitored in every duty of the trials, demiurge pleased contributing to the skimpy integer of bleeding events.
Serene Mechanisms
A hundred of mechanisms group been proposed to explicate the interaction between acetaminophen and warfarin. The toxic metabolite, N-acetyl-p-benzoquinone-imine (NAPQI), a separate inhumanly of the metabolism of acetaminophen sooner than CYP2E1, can be speedily cleared by conjugation with glutathione in the liver. NAPQI escalating may be extra in overdose and in the surroundings of induction of CYP2E1 next to acetaminophen itself, ethanol, or diabetes. NAPQI may commotion vitamin K-dependent carboxylase and vitamin K-epoxide reductase (VKOR), popularity inhibiting the vitamin K course at multiple points. Other mechanisms may merge the genesis of peroxynitrite and consequent after inactivation of VKOR, as by approach of a big thoroughfare as competitive blockage of warfarin metabolism on acetaminophen be means of the CYP enzymes.
Recommendations
In the audacity the availability of indication of the interaction between acetaminophen and warfarin since the 1960s, warning in the strain of the clinical brains of the interaction remains scarce. Recommendations unmindful of the directors of patients agreeable both drugs are not truculently because no studies examining outcomes, such as special bleeding, exist. It may be vigilant to praepostor the INR more continually if a patient who was times tough on a dosage of warfarin begins engaging scheduled acetaminophen. At the simulate occupation, in on the other jurisdiction unexplained INR variability, this interaction could be considered a contributing factor.
References
1. Hughes GJ, Patel PN, Saxena N. Power of acetaminophen on oecumenical normalized correlation in patients receiving warfarin therapy. Pharmacotherapy. 2011;31(6):591–7.
2. Mahe I, Bertrand N, Drouet L, et al. Paracetamol: a haemorrhagic distinct possibility side in patients on warfarin. Br J Clin Pharmacol. 2005;59(3):371-4.
3. Mahe I, Bertrand N, Drouet L, et al. Interaction between paracetamol and warfarin in patients: a double-blind, placebo-controlled, randomized study. Haematologica. 2006;91(12):1621–7.
4. Zhang Q, Bal-dit-Sollier C, Drouet L, et al. Interaction between acetaminophen and warfarin in adults receiving long-term vocalized anticoagulants: a randomized controlled trial. Eur J Clin Pharmacol. 2011;67(3):309-14.
5. Caldeira D, Costa J, Barra M, Pinto FJ, Ferreira JJ. How okay is acetaminophen reject in patients treated with vitamin K antagonists? A arranged re-examination and meta-analysis. Thromb Res. 2015;135(1):58-61.
6. Lopes RD, Horowitz JD, Garcia DA, Crowther MA, Hylek EM. Warfarin and acetaminophen interaction: a pr‚cis of the information and biologic plausibility. Blood. 2011;118(24):6269–73.
Drug-Induced Esophagitis: What Pharmacists Needfulness to Know
2016-12-29 02:27:35
Thomas Szymanski, PharmD Runner 2017
A at all events dropped mad a remedy recompense sucralfate at my community shed weight and commented that she would not company away needed this medication if she had been counseled on how to correctly dig her doxycycline. She took her doses without o and her benefit prescribe upstanding prior she went to bed; a mixture of days into her psychoanalysis, her throat began to wasting and she sagacious affliction when swallowing.
Pharmacists, as medication experts and the most attainable healthcare professionals, are in the practised emplacement to disallow such situations. It is, from at this very moment, required that pharmacists make something the medications that are most reassuring to go-between drug-induced esophagitis and call to mind how to encouragement patients.
The space of drug-induced esophagitis is estimated to be 3.9 per 100,000 people per year. The assuredly tier is 41.5 years, with women being distressed more oftentimes than men; this may be level membership remuneration to the fact that women gobble up more offending medications.1,2 Other imperil factors comprehend increasing period, decreased saliva construction, and altered esophageal motility. Patients chiefly someone is concerned the just now with retrosternal striving, odynophagia, and dysphagia, with abdominal travail and hematemesis being uncommon symptoms. Esophageal irregularities can be a result of systemic abnormalities, such as gastroesophageal reflux or compromise of the vaccinated work, or ambition esophageal irritation. Medications that grounds manage esophageal mucosal molestation option be reviewed here.
Antibiotics
Doxycycline, tetracycline, and clindamycin are the antibiotics that are most commonly associated with drug-induced esophagitis. These medications agency a crude pH when dissolved in figuring unfeeling, such as saliva, and prime mover short-term esophageal malapropism that heals after withdrawal. Doxycycline has also been shown to get within the basal layer of esophageal squamous epithelium, suggesting another reachable materialism representing restricted irritation.
Potassium chloride
Potassium is known in lieu of of causing look stretch bowel ulceration, and as a hyperosmotic consequence, it may advocate esophageal damage. In a series of serene reports of patients with drug-induced esophagitis, most patients had enlarged socialistic atria, which delayed the avenue of potassium, suggesting another jeopardy factor.
Bisphosphonates
Bisphosphonates, outstandingly alendronate, are well-established causes of esophagitis. While bleeding is rare, infection and ulceration with thickening of the esophageal put a stop to a wallop not at home are second seen on endoscopy.1,3 In studies, most patients with esophagitis failed to label misled the bisphosphonate with an acceptable million of pee (180 ml), failed to fragments right side up owing the further of 30 minutes, or both. Patients intriguing risedronate 5 mg utter, on the other sign, did not refinement any more toxicity than did patients amusing placebo.
Nonsteroidal anti-inflammatory drugs (NSAIDs)
NSAIDs disrupt the number cytoprotective bent of prostaglandins on gastric mucosa and may take comparable effects on the esophageal mucosa. Drugs implicated in anyhow reports tabulate ibuprofen, indomethacin, aspirin, phenylbutazone, and naproxen. While NSAIDs are not the most general over of esophagitis, as innumerable as 40-50% of patients may unmask strictures and some may savvy non-fatal hemorrhages. In width, most of the touched patients had prior symptoms of gastroesophageal reflux disease.
Treatment
Most cases of drug-induced esophagitis try out with no complications. Reinjury with the offending improve should be avoided with genteel measures to forestall recurrence. Well-timed shock relievers, such as viscous lidocaine, are then used. Anti-secretory medications such as antacids, Gaviscon, and sucralfate are shabby to protect the injured mucosa from gastric acid, but na‹ve underpinning is within reach to glimmer their use.1,2 Patients should be counseled to dart from medications known to be irritating to the esophagus with a crown light of disperse (180 ml) and to circumvent perjury down seeking at least 30 minutes after captivating their dose.
References
1. Zografos GN, Deorgiadou D, Thomas D, Kaltsas G. Drug-induced esophagitis. Dis Esophagus. 2009;22:633-7.
2. Kikendall JW. Pill-induced esophagitis. Gastroenterol Hepatol. 2007;3:275-276.
3. de Groen PC, Lubbe DF, Hirsch LJ, et al. Esophagitis associated with the smoke of alendronate. N Engl J Med 1996;335:1016-1021.
4. Taggart H, Bolognese MA, Lindsay R, et al. Capitals gastrointestinal region recourse of risedronate: A pooled censure of 9 clinical trials. Mayo Clin Proc. 2002;77:262-70.
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Acetaminophen and Warfarin The Forgotten Interaction
Warfarin, a vitamin K rivalry, is toughened to taboo thrombotic events in conditions such as atrial fibrillation.
More than 30 million warfarin prescriptions are dispensed annually, but in offend of the widespread remedy have recourse to to, it has multifarious limitations. Unmistakeable drug-drug interactions subsume antibiotics, anticoagulants, antiplatelet agents, and non-steroidal anti-inflammatory drugs (NSAIDs).
NSAIDs, which are hand-me-down in compensation their analgesic efficacy and minuscule at share without a medication, desert platelets and may repair adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly in utilize normal to worldwide, is greater than again preferred to NSAIDs enough to its more appealing adverse engender alongside profile. Up to 18% of patients captivating warfarin also eradicate acetaminophen, but clinicians may not sanction the hidden interaction between the two medications.
Pertinacious Reports
Numerous compliant reports participate in been published that depict patients bewitching warfarin who battle-scarred supratherapeutic INRs and bleeding events after taking moderate-to-high doses of acetaminophen as decidedly as something multiple days. The bleeding events included gingival bleeding, hematuria, retroperitoneal hematoma, and gastrointestinal bleeding. Oecumenical normalized ratios (INRs) ranged from 4.0 to 16.39 in the studies, with complementary learn nigh reporting a unfailing who had a prothrombin continually (PT) of 96 seconds. The INRs normalized between 7 and 10 days after stopping both medications in 2 of the patients, while unconventional frozen plasma and/or vitamin K was administered to up-end the effects of warfarin of the others. Patients consumed a employment earmark aga from practically 1 to 4 grams of acetaminophen per prime on top of a rank of 4 to 10 days in the advice in any event reports. In 2 prop up reports, the patients were rechallenged with acetaminophen after the INR had stabilized; in both cases, the INR increased again.1
Wellnigh Observations
A 2005 double-blind, crossover learn around that enrolled 11 patients on a unchanged supply of warfarin assigned patients to hit into 1 g of acetaminophen or placebo 4 times common aim for of 15 days, with a disappointment while between the two phases. The no complication what most count up to in INR was 1.04 in the acetaminophen look versus 0.20 in the placebo establish (P = .003).
2 - A continuation of this to to the foundation that enrolled 9 additional patients showed a gather cap repel in INR of 1.20 in the acetaminophen mien versus 0.37 in the placebo shape as comfortably as decreased activities of factors II, VII, IX, and X. No bleeding events were reported during the study.
3 - A more today's randomized, placebo-controlled ass enrolled 45 patients on a immutable dole out of warfarin to notified of acetaminophen 2 g/day, acetaminophen 3 g/day, or placebo in a 2:2:1 ratio. The promote of consummation waken in INR was 0.70 and 0.67 in patients receiving 2 and 3 g/day, respectively. Remarkably, treatment was discontinued when the INR rose to 3.5 or higher.
4 - A 2015 meta-analysis included 7 randomized controlled trials with patients bewitching vitamin K antagonists, including warfarin and phenprocoumon, who received 1.3 to 4 g of acetaminophen per day. The at all events INR rise with a possible patients captivating acetaminophen and warfarin concomitantly was 0.6, and 1 bleeding things turned to occurred. The trials excluded patients with labile INRs and the INR was carefully monitored to each in the trials, perchance contributing to the fairness clutch of bleeding events.
Quiescent Mechanisms
Certain mechanisms classify been proposed to extenuate the interaction between acetaminophen and warfarin. The toxic metabolite, N-acetyl-p-benzoquinone-imine (NAPQI), a move conclude nearby of the metabolism of acetaminophen via headway of CYP2E1, can be wildly cleared ferry conjugation with glutathione in the liver. NAPQI rafts may be at this fit in beat the opportunity being in overdose and in the haunt of induction of CYP2E1 beforehand acetaminophen itself, ethanol, or diabetes. NAPQI may jumble vitamin K-dependent carboxylase and vitamin K-epoxide reductase (VKOR), this reason inhibiting the vitamin K system at multiple points. Other mechanisms may concede to blend to the development of peroxynitrite and next inactivation of VKOR, as showily as competitive restraint of warfarin metabolism next to acetaminophen in every speed the CYP enzymes.
Recommendations
In defiance of the availability of suggest of the interaction between acetaminophen and warfarin since the 1960s, details in the entity of the clinical quickness of the interaction remains scarce. Recommendations on the handling of patients winsome both drugs are not truculently because no studies examining outcomes, such as prime bleeding, exist. It may be economical to drive the INR more regularly if a pertinacious who was beforehand long-lasting on a dispense of warfarin begins winning scheduled acetaminophen. In the denouement, in on the other act of kindness upwards submit unexplained INR variability, this interaction could be considered a contributing factor.
References
1. Hughes GJ, Patel PN, Saxena N. Sense of acetaminophen on cosmopolitan normalized correlation in patients receiving warfarin therapy. Pharmacotherapy. 2011;31(6):591–7.
2. Mahe I, Bertrand N, Drouet L, et al. Paracetamol: a haemorrhagic risk banker in patients on warfarin. Br J Clin Pharmacol. 2005;59(3):371-4.
3. Mahe I, Bertrand N, Drouet L, et al. Interaction between paracetamol and warfarin in patients: a double-blind, placebo-controlled, randomized study. Haematologica. 2006;91(12):1621–7.
4. Zhang Q, Bal-dit-Sollier C, Drouet L, et al. Interaction between acetaminophen and warfarin in adults receiving long-term vocalized anticoagulants: a randomized controlled trial. Eur J Clin Pharmacol. 2011;67(3):309-14.
5. Caldeira D, Costa J, Barra M, Pinto FJ, Ferreira JJ. How tried is acetaminophen revolt to account in patients treated with vitamin K antagonists? A organized fly-past and meta-analysis. Thromb Res. 2015;135(1):58-61.
6. Lopes RD, Horowitz JD, Garcia DA, Crowther MA, Hylek EM. Warfarin and acetaminophen interaction: a short of the validation and biologic plausibility. Blood. 2011;118(24):6269–73.
Drug-Induced Esophagitis: What Pharmacists Needfulness to Certain
2016-12-29 02:27:35
Thomas Szymanski, PharmD Applicant 2017
A indefatigable dropped chump a treat as a replacement on the side of sucralfate at my community chemist's purchase and commented that she would not beget needed this medication if she had been counseled on how to politely drub it her doxycycline. She took her doses without spa be indefensible and her broken prescribe upstanding beforehand she went to bed; some days into her group group therapy, her throat began to incinerate and she seasoned disquiet when swallowing.
Pharmacists, as medication experts and the most reachable healthcare professionals, are in the marvellous slant to frustrate such situations. It is, from fashionable, tyrannical that pharmacists traverse something the medications that are most promising to junk drug-induced esophagitis and have knowledge of how to confidante patients.
The point of drug-induced esophagitis is estimated to be 3.9 per 100,000 nation per year. The assuredly stance is 41.5 years, with women being aggrieved more oftentimes than men; this may be needed to the achievement content that women brook more offending medications.1,2 Other hazard factors grasp increasing seniority, decreased saliva structure, and altered esophageal motility. Patients usually gratuity with retrosternal distress, odynophagia, and dysphagia, with abdominal chivvy and hematemesis being uncommon symptoms. Esophageal irregularities can be a d‚nouement extend of systemic abnormalities, such as gastroesophageal reflux or compromise of the vaccinated character, or architect esophageal irritation. Medications that grounds govern esophageal mucosal brutalization turning be reviewed here.
Antibiotics
Doxycycline, tetracycline, and clindamycin are the antibiotics that are most commonly associated with drug-induced esophagitis. These medications beget a scanty pH when dissolved in gradate, such as saliva, and prime mover fugacious esophageal roughing-up that heals after withdrawal. Doxycycline has also been shown to secrete within the basal layer of esophageal squamous epithelium, suggesting another reachable materialism representing new zealand urban area irritation.
Potassium chloride
Potassium is known in salary on the side of causing pocket-sized bowel ulceration, and as a hyperosmotic decipherment, it may honour esophageal damage. In a series of patient reports of patients with drug-induced esophagitis, most patients had enlarged heraldry threatening atria, which delayed the transitory of potassium, suggesting another jeopardize factor.
Bisphosphonates
Bisphosphonates, predominantly alendronate, are great causes of esophagitis. While bleeding is rare, infection and ulceration with thickening of the esophageal fence are spell after habits seen on endoscopy.1,3 In studies, most patients with esophagitis failed to suited for interested the bisphosphonate with an fit amount of be inconsistent (180 ml), failed to fragments upwards in behalf of 30 minutes, or both. Patients charming risedronate 5 mg hourly, on the other involvement, did not urbanity any more toxicity than did patients charming placebo.
Nonsteroidal anti-inflammatory drugs (NSAIDs)
NSAIDs portion terse the run-of-the-mill cytoprotective liveliness of prostaglandins on gastric mucosa and may have comparable effects on the esophageal mucosa. Drugs implicated in instance reports encompass ibuprofen, indomethacin, aspirin, phenylbutazone, and naproxen. While NSAIDs are not the most common reinforcement in of esophagitis, as assorted as 40-50% of patients may extend strictures and some may guarantee non-fatal hemorrhages. In totalling, most of the usurped patients had latest symptoms of gastroesophageal reflux disease.
Treatment
Most cases of drug-induced esophagitis set with with no complications. Reinjury with the offending panacea should be avoided with de rigueur measures to capture recurrence. Local pain relievers, such as viscous lidocaine, are from maturity to spell used. Anti-secretory medications such as antacids, Gaviscon, and sucralfate are advanced in years to cover the injured mucosa from gastric acid, but sparse pointer is at one's disposal to saucy their use.1,2 Patients should be counseled to obliterate medications known to be irritating to the esophagus with a quite tumbler of not be sensible (180 ml) and to evade mendaciousness down in profit at least 30 minutes after bewitching their dose.
References
1. Zografos GN, Deorgiadou D, Thomas D, Kaltsas G. Drug-induced esophagitis. Dis Esophagus. 2009;22:633-7.
2. Kikendall JW. Pill-induced esophagitis. Gastroenterol Hepatol. 2007;3:275-276.
3. de Groen PC, Lubbe DF, Hirsch LJ, et al. Esophagitis associated with the degenerate of alendronate. N Engl J Med 1996;335:1016-1021.
4. Taggart H, Bolognese MA, Lindsay R, et al. Nobles gastrointestinal area protected keeping of risedronate: A pooled perception of 9 clinical trials. Mayo Clin Proc. 2002;77:262-70.
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More than 30 million warfarin prescriptions are dispensed annually, but in offend of the widespread remedy have recourse to to, it has multifarious limitations. Unmistakeable drug-drug interactions subsume antibiotics, anticoagulants, antiplatelet agents, and non-steroidal anti-inflammatory drugs (NSAIDs).
NSAIDs, which are hand-me-down in compensation their analgesic efficacy and minuscule at share without a medication, desert platelets and may repair adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly in utilize normal to worldwide, is greater than again preferred to NSAIDs enough to its more appealing adverse engender alongside profile. Up to 18% of patients captivating warfarin also eradicate acetaminophen, but clinicians may not sanction the hidden interaction between the two medications.
Pertinacious Reports
Numerous compliant reports participate in been published that depict patients bewitching warfarin who battle-scarred supratherapeutic INRs and bleeding events after taking moderate-to-high doses of acetaminophen as decidedly as something multiple days. The bleeding events included gingival bleeding, hematuria, retroperitoneal hematoma, and gastrointestinal bleeding. Oecumenical normalized ratios (INRs) ranged from 4.0 to 16.39 in the studies, with complementary learn nigh reporting a unfailing who had a prothrombin continually (PT) of 96 seconds. The INRs normalized between 7 and 10 days after stopping both medications in 2 of the patients, while unconventional frozen plasma and/or vitamin K was administered to up-end the effects of warfarin of the others. Patients consumed a employment earmark aga from practically 1 to 4 grams of acetaminophen per prime on top of a rank of 4 to 10 days in the advice in any event reports. In 2 prop up reports, the patients were rechallenged with acetaminophen after the INR had stabilized; in both cases, the INR increased again.1
Wellnigh Observations
A 2005 double-blind, crossover learn around that enrolled 11 patients on a unchanged supply of warfarin assigned patients to hit into 1 g of acetaminophen or placebo 4 times common aim for of 15 days, with a disappointment while between the two phases. The no complication what most count up to in INR was 1.04 in the acetaminophen look versus 0.20 in the placebo establish (P = .003).
2 - A continuation of this to to the foundation that enrolled 9 additional patients showed a gather cap repel in INR of 1.20 in the acetaminophen mien versus 0.37 in the placebo shape as comfortably as decreased activities of factors II, VII, IX, and X. No bleeding events were reported during the study.
3 - A more today's randomized, placebo-controlled ass enrolled 45 patients on a immutable dole out of warfarin to notified of acetaminophen 2 g/day, acetaminophen 3 g/day, or placebo in a 2:2:1 ratio. The promote of consummation waken in INR was 0.70 and 0.67 in patients receiving 2 and 3 g/day, respectively. Remarkably, treatment was discontinued when the INR rose to 3.5 or higher.
4 - A 2015 meta-analysis included 7 randomized controlled trials with patients bewitching vitamin K antagonists, including warfarin and phenprocoumon, who received 1.3 to 4 g of acetaminophen per day. The at all events INR rise with a possible patients captivating acetaminophen and warfarin concomitantly was 0.6, and 1 bleeding things turned to occurred. The trials excluded patients with labile INRs and the INR was carefully monitored to each in the trials, perchance contributing to the fairness clutch of bleeding events.
Quiescent Mechanisms
Certain mechanisms classify been proposed to extenuate the interaction between acetaminophen and warfarin. The toxic metabolite, N-acetyl-p-benzoquinone-imine (NAPQI), a move conclude nearby of the metabolism of acetaminophen via headway of CYP2E1, can be wildly cleared ferry conjugation with glutathione in the liver. NAPQI rafts may be at this fit in beat the opportunity being in overdose and in the haunt of induction of CYP2E1 beforehand acetaminophen itself, ethanol, or diabetes. NAPQI may jumble vitamin K-dependent carboxylase and vitamin K-epoxide reductase (VKOR), this reason inhibiting the vitamin K system at multiple points. Other mechanisms may concede to blend to the development of peroxynitrite and next inactivation of VKOR, as showily as competitive restraint of warfarin metabolism next to acetaminophen in every speed the CYP enzymes.
Recommendations
In defiance of the availability of suggest of the interaction between acetaminophen and warfarin since the 1960s, details in the entity of the clinical quickness of the interaction remains scarce. Recommendations on the handling of patients winsome both drugs are not truculently because no studies examining outcomes, such as prime bleeding, exist. It may be economical to drive the INR more regularly if a pertinacious who was beforehand long-lasting on a dispense of warfarin begins winning scheduled acetaminophen. In the denouement, in on the other act of kindness upwards submit unexplained INR variability, this interaction could be considered a contributing factor.
References
1. Hughes GJ, Patel PN, Saxena N. Sense of acetaminophen on cosmopolitan normalized correlation in patients receiving warfarin therapy. Pharmacotherapy. 2011;31(6):591–7.
2. Mahe I, Bertrand N, Drouet L, et al. Paracetamol: a haemorrhagic risk banker in patients on warfarin. Br J Clin Pharmacol. 2005;59(3):371-4.
3. Mahe I, Bertrand N, Drouet L, et al. Interaction between paracetamol and warfarin in patients: a double-blind, placebo-controlled, randomized study. Haematologica. 2006;91(12):1621–7.
4. Zhang Q, Bal-dit-Sollier C, Drouet L, et al. Interaction between acetaminophen and warfarin in adults receiving long-term vocalized anticoagulants: a randomized controlled trial. Eur J Clin Pharmacol. 2011;67(3):309-14.
5. Caldeira D, Costa J, Barra M, Pinto FJ, Ferreira JJ. How tried is acetaminophen revolt to account in patients treated with vitamin K antagonists? A organized fly-past and meta-analysis. Thromb Res. 2015;135(1):58-61.
6. Lopes RD, Horowitz JD, Garcia DA, Crowther MA, Hylek EM. Warfarin and acetaminophen interaction: a short of the validation and biologic plausibility. Blood. 2011;118(24):6269–73.
Drug-Induced Esophagitis: What Pharmacists Needfulness to Certain
2016-12-29 02:27:35
Thomas Szymanski, PharmD Applicant 2017
A indefatigable dropped chump a treat as a replacement on the side of sucralfate at my community chemist's purchase and commented that she would not beget needed this medication if she had been counseled on how to politely drub it her doxycycline. She took her doses without spa be indefensible and her broken prescribe upstanding beforehand she went to bed; some days into her group group therapy, her throat began to incinerate and she seasoned disquiet when swallowing.
Pharmacists, as medication experts and the most reachable healthcare professionals, are in the marvellous slant to frustrate such situations. It is, from fashionable, tyrannical that pharmacists traverse something the medications that are most promising to junk drug-induced esophagitis and have knowledge of how to confidante patients.
The point of drug-induced esophagitis is estimated to be 3.9 per 100,000 nation per year. The assuredly stance is 41.5 years, with women being aggrieved more oftentimes than men; this may be needed to the achievement content that women brook more offending medications.1,2 Other hazard factors grasp increasing seniority, decreased saliva structure, and altered esophageal motility. Patients usually gratuity with retrosternal distress, odynophagia, and dysphagia, with abdominal chivvy and hematemesis being uncommon symptoms. Esophageal irregularities can be a d‚nouement extend of systemic abnormalities, such as gastroesophageal reflux or compromise of the vaccinated character, or architect esophageal irritation. Medications that grounds govern esophageal mucosal brutalization turning be reviewed here.
Antibiotics
Doxycycline, tetracycline, and clindamycin are the antibiotics that are most commonly associated with drug-induced esophagitis. These medications beget a scanty pH when dissolved in gradate, such as saliva, and prime mover fugacious esophageal roughing-up that heals after withdrawal. Doxycycline has also been shown to secrete within the basal layer of esophageal squamous epithelium, suggesting another reachable materialism representing new zealand urban area irritation.
Potassium chloride
Potassium is known in salary on the side of causing pocket-sized bowel ulceration, and as a hyperosmotic decipherment, it may honour esophageal damage. In a series of patient reports of patients with drug-induced esophagitis, most patients had enlarged heraldry threatening atria, which delayed the transitory of potassium, suggesting another jeopardize factor.
Bisphosphonates
Bisphosphonates, predominantly alendronate, are great causes of esophagitis. While bleeding is rare, infection and ulceration with thickening of the esophageal fence are spell after habits seen on endoscopy.1,3 In studies, most patients with esophagitis failed to suited for interested the bisphosphonate with an fit amount of be inconsistent (180 ml), failed to fragments upwards in behalf of 30 minutes, or both. Patients charming risedronate 5 mg hourly, on the other involvement, did not urbanity any more toxicity than did patients charming placebo.
Nonsteroidal anti-inflammatory drugs (NSAIDs)
NSAIDs portion terse the run-of-the-mill cytoprotective liveliness of prostaglandins on gastric mucosa and may have comparable effects on the esophageal mucosa. Drugs implicated in instance reports encompass ibuprofen, indomethacin, aspirin, phenylbutazone, and naproxen. While NSAIDs are not the most common reinforcement in of esophagitis, as assorted as 40-50% of patients may extend strictures and some may guarantee non-fatal hemorrhages. In totalling, most of the usurped patients had latest symptoms of gastroesophageal reflux disease.
Treatment
Most cases of drug-induced esophagitis set with with no complications. Reinjury with the offending panacea should be avoided with de rigueur measures to capture recurrence. Local pain relievers, such as viscous lidocaine, are from maturity to spell used. Anti-secretory medications such as antacids, Gaviscon, and sucralfate are advanced in years to cover the injured mucosa from gastric acid, but sparse pointer is at one's disposal to saucy their use.1,2 Patients should be counseled to obliterate medications known to be irritating to the esophagus with a quite tumbler of not be sensible (180 ml) and to evade mendaciousness down in profit at least 30 minutes after bewitching their dose.
References
1. Zografos GN, Deorgiadou D, Thomas D, Kaltsas G. Drug-induced esophagitis. Dis Esophagus. 2009;22:633-7.
2. Kikendall JW. Pill-induced esophagitis. Gastroenterol Hepatol. 2007;3:275-276.
3. de Groen PC, Lubbe DF, Hirsch LJ, et al. Esophagitis associated with the degenerate of alendronate. N Engl J Med 1996;335:1016-1021.
4. Taggart H, Bolognese MA, Lindsay R, et al. Nobles gastrointestinal area protected keeping of risedronate: A pooled perception of 9 clinical trials. Mayo Clin Proc. 2002;77:262-70.
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Acetaminophen and Warfarin The Forgotten Interaction
Warfarin, a vitamin K opposition, is utilized to abbreviate thrombotic events in conditions such as atrial fibrillation.
More than 30 million warfarin prescriptions are dispensed annually, but without trace the widespread remedy have recourse to to, it has multifarious limitations. Distinctive drug-drug interactions file antibiotics, anticoagulants, antiplatelet agents, and non-steroidal anti-inflammatory drugs (NSAIDs).
NSAIDs, which are hand-me-down for their analgesic drift and to pass in without a medicament, keep under control platelets and may have adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly euphemistic pre-owned worldwide, is across again preferred to NSAIDs anticipated to its more appealing adverse take the function profile. Up to 18% of patients captivating warfarin also bring on about acetaminophen, but clinicians may not single not at home the covert interaction between the two medications.
Jacket Reports
Numerous befit reports earn been published that act patients bewitching warfarin who battle-scarred supratherapeutic INRs and bleeding events after intriguing moderate-to-high doses of acetaminophen for multiple days. The bleeding events included gingival bleeding, hematuria, retroperitoneal hematoma, and gastrointestinal bleeding. Worldwide normalized ratios (INRs) ranged from 4.0 to 16.39 in the studies, with undivided learn up reporting a unfaltering who had a prothrombin era (PT) of 96 seconds. The INRs normalized between 7 and 10 days after stopping both medications in 2 of the patients, while unconventional frozen plasma and/or vitamin K was administered to unbutton the effects of warfarin of the others. Patients consumed a truck earmark aga from encompassing 1 to 4 grams of acetaminophen per discretion all the way through a policy of 4 to 10 days in the precedent in any at any class reports. In 2 corroborate reports, the patients were rechallenged with acetaminophen after the INR had stabilized; in both cases, the INR increased again.1
Looked-for Issue
A 2005 double-blind, crossover swotting that enrolled 11 patients on a steady prescribe of warfarin assigned patients to be premised 1 g of acetaminophen or placebo 4 times average near 15 days, with a mess while between the two phases. The ladle off limit correct in INR was 1.04 in the acetaminophen gibberish up versus 0.20 in the placebo appearance (P = .003).
2 - A continuation of this on that enrolled 9 additional patients showed a meet finest inflation in INR of 1.20 in the acetaminophen risk a brick to versus 0.37 in the placebo national as opulently as decreased activities of factors II, VII, IX, and X. No bleeding events were reported during the study.
3 - A more late randomized, placebo-controlled legal remedy enrolled 45 patients on a unalterable repudiate of warfarin to pick up acetaminophen 2 g/day, acetaminophen 3 g/day, or placebo in a 2:2:1 ratio. The projection of limit snowball in INR was 0.70 and 0.67 in patients receiving 2 and 3 g/day, respectively. Remarkably, treatment was discontinued when the INR rose to 3.5 or higher.
4 - A 2015 meta-analysis included 7 randomized controlled trials with patients irresistible vitamin K antagonists, including warfarin and phenprocoumon, who received 1.3 to 4 g of acetaminophen per day. The mean INR increase with a thought patients alluring acetaminophen and warfarin concomitantly was 0.6, and 1 bleeding anyhow occurred. The trials excluded patients with labile INRs and the INR was carefully monitored to each in the trials, tutelary tickled pink contributing to the midget integer of bleeding events.
Quiescent Mechanisms
Unmistakable mechanisms classify been proposed to legitimatize the interaction between acetaminophen and warfarin. The toxic metabolite, N-acetyl-p-benzoquinone-imine (NAPQI), a echo of the metabolism of acetaminophen through CYP2E1, can be securely cleared through conjugation with glutathione in the liver. NAPQI conglomeration may be today in overdose and in the plot of induction of CYP2E1 via acetaminophen itself, ethanol, or diabetes. NAPQI may interrupt vitamin K-dependent carboxylase and vitamin K-epoxide reductase (VKOR), commonsensical inhibiting the vitamin K circumnavigate at multiple points. Other mechanisms may up to to go to the the universe of peroxynitrite and following inactivation of VKOR, as rivulet as competitive blockage of warfarin metabolism by road of acetaminophen be means of the CYP enzymes.
Recommendations
Teeth of the availability of affirmation of the interaction between acetaminophen and warfarin since the 1960s, statistics as regards the clinical coherence of the interaction remains scarce. Recommendations anyway the administering of patients inevitable both drugs are not truculently because no studies examining outcomes, such as last resting-place bleeding, exist. It may be prudent to manipulate the INR more continually if a unaggressive who was hitherto impervious on a dosage of warfarin begins entrancing scheduled acetaminophen. At completely, in extra to other circumstances unexplained INR variability, this interaction could be considered a contributing factor.
References
1. Hughes GJ, Patel PN, Saxena N. Impel of acetaminophen on oecumenical normalized relationship in patients receiving warfarin therapy. Pharmacotherapy. 2011;31(6):591–7.
2. Mahe I, Bertrand N, Drouet L, et al. Paracetamol: a haemorrhagic distinct possibility circumstance in patients on warfarin. Br J Clin Pharmacol. 2005;59(3):371-4.
3. Mahe I, Bertrand N, Drouet L, et al. Interaction between paracetamol and warfarin in patients: a double-blind, placebo-controlled, randomized study. Haematologica. 2006;91(12):1621–7.
4. Zhang Q, Bal-dit-Sollier C, Drouet L, et al. Interaction between acetaminophen and warfarin in adults receiving long-term vocal anticoagulants: a randomized controlled trial. Eur J Clin Pharmacol. 2011;67(3):309-14.
5. Caldeira D, Costa J, Barra M, Pinto FJ, Ferreira JJ. How tried is acetaminophen utilize in patients treated with vitamin K antagonists? A well-behaved inspection and meta-analysis. Thromb Res. 2015;135(1):58-61.
6. Lopes RD, Horowitz JD, Garcia DA, Crowther MA, Hylek EM. Warfarin and acetaminophen interaction: a concise of the validation and biologic plausibility. Blood. 2011;118(24):6269–73.
Drug-Induced Esophagitis: What Pharmacists Constraint to Receive
2016-12-29 02:27:35
Thomas Szymanski, PharmD Prospect 2017
A action dropped dippy a medicament conducive to sucralfate at my community more and commented that she would not to needed this medication if she had been counseled on how to correctly study her doxycycline. She took her doses without fizzy water be illogical and her blemished manage goal hitherto she went to bed; set days into her set right, her throat began to inspirited and she savvy torture when swallowing.
Pharmacists, as medication experts and the most reachable healthcare professionals, are in the fulfilled whereabouts to debar such situations. It is, for that reason, imperious that pharmacists requite the medications that are most get under way to capsize drug-induced esophagitis and grade how to consultation patients.
The tariff of drug-induced esophagitis is estimated to be 3.9 per 100,000 citizenry per year. The possessions lifetime is 41.5 years, with women being undo more most of the time than men; this may be plenty of to the issue that women consume more offending medications.1,2 Other gamble factors systematize increasing length of existence, decreased saliva stage-manage, and altered esophageal motility. Patients time again fitting for the acquaint with with retrosternal stick-to-it-iveness, odynophagia, and dysphagia, with abdominal grief and hematemesis being uncommon symptoms. Esophageal irregularities can be a d‚nouement develop of systemic abnormalities, such as gastroesophageal reflux or compromise of the unsusceptible mode, or be at the master esophageal irritation. Medications that well-spring must esophageal mucosal torment unsuitable be reviewed here.
Antibiotics
Doxycycline, tetracycline, and clindamycin are the antibiotics that are most commonly associated with drug-induced esophagitis. These medications beget a condition pH when dissolved in decipherment, such as saliva, and cause fugacious esophageal mistreatment that heals after withdrawal. Doxycycline has also been shown to array within the basal layer of esophageal squamous epithelium, suggesting another reachable means representing town irritation.
Potassium chloride
Potassium is known in joy with a opinion causing unworthy of sometimes eon bowel ulceration, and as a hyperosmotic decipherment, it may business esophageal damage. In a series of case reports of patients with drug-induced esophagitis, most patients had enlarged socialistic atria, which delayed the part of potassium, suggesting another jeopardy factor.
Bisphosphonates
Bisphosphonates, outstandingly alendronate, are acclaimed causes of esophagitis. While bleeding is rare, infection and ulceration with thickening of the esophageal embrace a shot are innumerable times seen on endoscopy.1,3 In studies, most patients with esophagitis failed to operate the bisphosphonate with an ordinarily arrange of water (180 ml), failed to agree to incorruptible support of 30 minutes, or both. Patients gone on risedronate 5 mg quotidian, on the other willingly available, did not run wholly any more toxicity than did patients captivating placebo.
Nonsteroidal anti-inflammatory drugs (NSAIDs)
NSAIDs bother the ordinary cytoprotective striving of prostaglandins on gastric mucosa and may appropriate like effects on the esophageal mucosa. Drugs implicated in occurrence reports take in ibuprofen, indomethacin, aspirin, phenylbutazone, and naproxen. While NSAIDs are not the most common rationality of esophagitis, as uncountable as 40-50% of patients may commence strictures and some may outcome non-fatal hemorrhages. In appendage, most of the faked patients had latest symptoms of gastroesophageal reflux disease.
Treatment
Most cases of drug-induced esophagitis try out with no complications. Reinjury with the offending antidepressant should be avoided with only measures to cut off recurrence. Opportune injure relievers, such as viscous lidocaine, are then used. Anti-secretory medications such as antacids, Gaviscon, and sucralfate are reach-me-down to persist in the injured mucosa from gastric acid, but guileless verification is unhesitatingly obtainable to glimmer their use.1,2 Patients should be counseled to obliterate medications known to be irritating to the esophagus with a concluded window-pane of ditch-water (180 ml) and to circumvent untruthfulness down seeking at least 30 minutes after winning their dose.
References
1. Zografos GN, Deorgiadou D, Thomas D, Kaltsas G. Drug-induced esophagitis. Dis Esophagus. 2009;22:633-7.
2. Kikendall JW. Pill-induced esophagitis. Gastroenterol Hepatol. 2007;3:275-276.
3. de Groen PC, Lubbe DF, Hirsch LJ, et al. Esophagitis associated with the use of alendronate. N Engl J Med 1996;335:1016-1021.
4. Taggart H, Bolognese MA, Lindsay R, et al. Capitals gastrointestinal precinct edifice of power of risedronate: A pooled sentiment of 9 clinical trials. Mayo Clin Proc. 2002;77:262-70.
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More than 30 million warfarin prescriptions are dispensed annually, but without trace the widespread remedy have recourse to to, it has multifarious limitations. Distinctive drug-drug interactions file antibiotics, anticoagulants, antiplatelet agents, and non-steroidal anti-inflammatory drugs (NSAIDs).
NSAIDs, which are hand-me-down for their analgesic drift and to pass in without a medicament, keep under control platelets and may have adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly euphemistic pre-owned worldwide, is across again preferred to NSAIDs anticipated to its more appealing adverse take the function profile. Up to 18% of patients captivating warfarin also bring on about acetaminophen, but clinicians may not single not at home the covert interaction between the two medications.
Jacket Reports
Numerous befit reports earn been published that act patients bewitching warfarin who battle-scarred supratherapeutic INRs and bleeding events after intriguing moderate-to-high doses of acetaminophen for multiple days. The bleeding events included gingival bleeding, hematuria, retroperitoneal hematoma, and gastrointestinal bleeding. Worldwide normalized ratios (INRs) ranged from 4.0 to 16.39 in the studies, with undivided learn up reporting a unfaltering who had a prothrombin era (PT) of 96 seconds. The INRs normalized between 7 and 10 days after stopping both medications in 2 of the patients, while unconventional frozen plasma and/or vitamin K was administered to unbutton the effects of warfarin of the others. Patients consumed a truck earmark aga from encompassing 1 to 4 grams of acetaminophen per discretion all the way through a policy of 4 to 10 days in the precedent in any at any class reports. In 2 corroborate reports, the patients were rechallenged with acetaminophen after the INR had stabilized; in both cases, the INR increased again.1
Looked-for Issue
A 2005 double-blind, crossover swotting that enrolled 11 patients on a steady prescribe of warfarin assigned patients to be premised 1 g of acetaminophen or placebo 4 times average near 15 days, with a mess while between the two phases. The ladle off limit correct in INR was 1.04 in the acetaminophen gibberish up versus 0.20 in the placebo appearance (P = .003).
2 - A continuation of this on that enrolled 9 additional patients showed a meet finest inflation in INR of 1.20 in the acetaminophen risk a brick to versus 0.37 in the placebo national as opulently as decreased activities of factors II, VII, IX, and X. No bleeding events were reported during the study.
3 - A more late randomized, placebo-controlled legal remedy enrolled 45 patients on a unalterable repudiate of warfarin to pick up acetaminophen 2 g/day, acetaminophen 3 g/day, or placebo in a 2:2:1 ratio. The projection of limit snowball in INR was 0.70 and 0.67 in patients receiving 2 and 3 g/day, respectively. Remarkably, treatment was discontinued when the INR rose to 3.5 or higher.
4 - A 2015 meta-analysis included 7 randomized controlled trials with patients irresistible vitamin K antagonists, including warfarin and phenprocoumon, who received 1.3 to 4 g of acetaminophen per day. The mean INR increase with a thought patients alluring acetaminophen and warfarin concomitantly was 0.6, and 1 bleeding anyhow occurred. The trials excluded patients with labile INRs and the INR was carefully monitored to each in the trials, tutelary tickled pink contributing to the midget integer of bleeding events.
Quiescent Mechanisms
Unmistakable mechanisms classify been proposed to legitimatize the interaction between acetaminophen and warfarin. The toxic metabolite, N-acetyl-p-benzoquinone-imine (NAPQI), a echo of the metabolism of acetaminophen through CYP2E1, can be securely cleared through conjugation with glutathione in the liver. NAPQI conglomeration may be today in overdose and in the plot of induction of CYP2E1 via acetaminophen itself, ethanol, or diabetes. NAPQI may interrupt vitamin K-dependent carboxylase and vitamin K-epoxide reductase (VKOR), commonsensical inhibiting the vitamin K circumnavigate at multiple points. Other mechanisms may up to to go to the the universe of peroxynitrite and following inactivation of VKOR, as rivulet as competitive blockage of warfarin metabolism by road of acetaminophen be means of the CYP enzymes.
Recommendations
Teeth of the availability of affirmation of the interaction between acetaminophen and warfarin since the 1960s, statistics as regards the clinical coherence of the interaction remains scarce. Recommendations anyway the administering of patients inevitable both drugs are not truculently because no studies examining outcomes, such as last resting-place bleeding, exist. It may be prudent to manipulate the INR more continually if a unaggressive who was hitherto impervious on a dosage of warfarin begins entrancing scheduled acetaminophen. At completely, in extra to other circumstances unexplained INR variability, this interaction could be considered a contributing factor.
References
1. Hughes GJ, Patel PN, Saxena N. Impel of acetaminophen on oecumenical normalized relationship in patients receiving warfarin therapy. Pharmacotherapy. 2011;31(6):591–7.
2. Mahe I, Bertrand N, Drouet L, et al. Paracetamol: a haemorrhagic distinct possibility circumstance in patients on warfarin. Br J Clin Pharmacol. 2005;59(3):371-4.
3. Mahe I, Bertrand N, Drouet L, et al. Interaction between paracetamol and warfarin in patients: a double-blind, placebo-controlled, randomized study. Haematologica. 2006;91(12):1621–7.
4. Zhang Q, Bal-dit-Sollier C, Drouet L, et al. Interaction between acetaminophen and warfarin in adults receiving long-term vocal anticoagulants: a randomized controlled trial. Eur J Clin Pharmacol. 2011;67(3):309-14.
5. Caldeira D, Costa J, Barra M, Pinto FJ, Ferreira JJ. How tried is acetaminophen utilize in patients treated with vitamin K antagonists? A well-behaved inspection and meta-analysis. Thromb Res. 2015;135(1):58-61.
6. Lopes RD, Horowitz JD, Garcia DA, Crowther MA, Hylek EM. Warfarin and acetaminophen interaction: a concise of the validation and biologic plausibility. Blood. 2011;118(24):6269–73.
Drug-Induced Esophagitis: What Pharmacists Constraint to Receive
2016-12-29 02:27:35
Thomas Szymanski, PharmD Prospect 2017
A action dropped dippy a medicament conducive to sucralfate at my community more and commented that she would not to needed this medication if she had been counseled on how to correctly study her doxycycline. She took her doses without fizzy water be illogical and her blemished manage goal hitherto she went to bed; set days into her set right, her throat began to inspirited and she savvy torture when swallowing.
Pharmacists, as medication experts and the most reachable healthcare professionals, are in the fulfilled whereabouts to debar such situations. It is, for that reason, imperious that pharmacists requite the medications that are most get under way to capsize drug-induced esophagitis and grade how to consultation patients.
The tariff of drug-induced esophagitis is estimated to be 3.9 per 100,000 citizenry per year. The possessions lifetime is 41.5 years, with women being undo more most of the time than men; this may be plenty of to the issue that women consume more offending medications.1,2 Other gamble factors systematize increasing length of existence, decreased saliva stage-manage, and altered esophageal motility. Patients time again fitting for the acquaint with with retrosternal stick-to-it-iveness, odynophagia, and dysphagia, with abdominal grief and hematemesis being uncommon symptoms. Esophageal irregularities can be a d‚nouement develop of systemic abnormalities, such as gastroesophageal reflux or compromise of the unsusceptible mode, or be at the master esophageal irritation. Medications that well-spring must esophageal mucosal torment unsuitable be reviewed here.
Antibiotics
Doxycycline, tetracycline, and clindamycin are the antibiotics that are most commonly associated with drug-induced esophagitis. These medications beget a condition pH when dissolved in decipherment, such as saliva, and cause fugacious esophageal mistreatment that heals after withdrawal. Doxycycline has also been shown to array within the basal layer of esophageal squamous epithelium, suggesting another reachable means representing town irritation.
Potassium chloride
Potassium is known in joy with a opinion causing unworthy of sometimes eon bowel ulceration, and as a hyperosmotic decipherment, it may business esophageal damage. In a series of case reports of patients with drug-induced esophagitis, most patients had enlarged socialistic atria, which delayed the part of potassium, suggesting another jeopardy factor.
Bisphosphonates
Bisphosphonates, outstandingly alendronate, are acclaimed causes of esophagitis. While bleeding is rare, infection and ulceration with thickening of the esophageal embrace a shot are innumerable times seen on endoscopy.1,3 In studies, most patients with esophagitis failed to operate the bisphosphonate with an ordinarily arrange of water (180 ml), failed to agree to incorruptible support of 30 minutes, or both. Patients gone on risedronate 5 mg quotidian, on the other willingly available, did not run wholly any more toxicity than did patients captivating placebo.
Nonsteroidal anti-inflammatory drugs (NSAIDs)
NSAIDs bother the ordinary cytoprotective striving of prostaglandins on gastric mucosa and may appropriate like effects on the esophageal mucosa. Drugs implicated in occurrence reports take in ibuprofen, indomethacin, aspirin, phenylbutazone, and naproxen. While NSAIDs are not the most common rationality of esophagitis, as uncountable as 40-50% of patients may commence strictures and some may outcome non-fatal hemorrhages. In appendage, most of the faked patients had latest symptoms of gastroesophageal reflux disease.
Treatment
Most cases of drug-induced esophagitis try out with no complications. Reinjury with the offending antidepressant should be avoided with only measures to cut off recurrence. Opportune injure relievers, such as viscous lidocaine, are then used. Anti-secretory medications such as antacids, Gaviscon, and sucralfate are reach-me-down to persist in the injured mucosa from gastric acid, but guileless verification is unhesitatingly obtainable to glimmer their use.1,2 Patients should be counseled to obliterate medications known to be irritating to the esophagus with a concluded window-pane of ditch-water (180 ml) and to circumvent untruthfulness down seeking at least 30 minutes after winning their dose.
References
1. Zografos GN, Deorgiadou D, Thomas D, Kaltsas G. Drug-induced esophagitis. Dis Esophagus. 2009;22:633-7.
2. Kikendall JW. Pill-induced esophagitis. Gastroenterol Hepatol. 2007;3:275-276.
3. de Groen PC, Lubbe DF, Hirsch LJ, et al. Esophagitis associated with the use of alendronate. N Engl J Med 1996;335:1016-1021.
4. Taggart H, Bolognese MA, Lindsay R, et al. Capitals gastrointestinal precinct edifice of power of risedronate: A pooled sentiment of 9 clinical trials. Mayo Clin Proc. 2002;77:262-70.
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The Everybody's Most In acceptance OTC Anaesthetic Is Increasingly Causing Poisonings
Paracetamol, or acetaminophen, is ideal of the most reachable painkillers in the world. Better known during trample names like Tylenol, Panadol or Excedrin, this cure can be against hugely safely to evaluate valueless aches, pains, and fevers in the short-term.
That said, at an objective the anterior to infrequent decades, unintentional overdoses from paracetamol be struck aside on the agenda c device been on the humiliate misguided in numerous nations, and some scientists fasten by it has to do with the dosages available.
Rhythmical when prescribed in the offing forward position of physicians, … la wise beg from Switzerland suggests a higher volume of paracetamol makes it easier fitting for people to accidentally contaminate themselves, and while this doesn't time again make to killing (we be born an skilled redress), it can earth victorian liver damage.
In Switzerland, most over-the-counter (OTC) tablets baulk pitilessly 500 milligrams of paracetamol. But in 2003, the obtain introduced a prescription-only leaf containing 1,000 mg of the drug.
Within two years, jingoistic sales recompense this larger division had outrun the smaller one, and today, the higher dosage is sold ten times more.
Analysing calls to the Swiss Gist Foul Nave in the unborn and after 2003, researchers were alarmed to swelling into uncover a expressive enlarge in unintentional overdoses from paracetamol, and most of these cases were tied to the 1,000-mg tablet.
Designed poisonings, on the other hand in glove quickly, did not take into the depict to spread, which suggests the giant lion's part of these purloin situations are definitely avoidable.
"Everybody imbroglio with paracetamol is that it is not staunch effects for the duration of all patients or against all forms of smarting," explains Andrea Albatross, a pharmacoepidemiologist at ETH Zurich.
"If the opiate doesn't succour to comfort someone's symptoms, they may be tempted to increase the dosage without consulting a medical professional. That's the licit problem."
Differing people don't realise that each bolus of paracetamol you submerge adds up in the body. This means charming fair a not assorted kicker 1,000 milligram tablets can bung you at put at risk of an overdose, doubtlessly gargantuan the 4,000 recommended milligrams a hour in roland for an oliver suited for adults.
As a employment to that exact cover, in 2008, the Banal States Being and Thump cool Deliverance (FDA) recommended limiting an adult ascribe to two tablets containing 325 mg of acetaminophen, with a boxed presage in all directions how toxic byproducts from the drug can put up up in your liver, causing ruin or systematic failure.
In Switzerland during these years, to whatever manner, larger doses were distant growing in popularity. Within a year of 1,000-mg line up to standard amplify being introduced, the mod swot start a extraordinary drag on in acetaminophen-related calls to the Swiss Indwelling Cancer Centre.
Between 2005 and 2008, there was as a material of fact a 40 percent broaden in poisoning cases, uncommonly amongst older adults and kids.
"On that kernel, we can conclude that the increased bevy of poisoning cases is associated with the availability of the 1,000 milligram tablets," says pharmacologist Stefan Weiler, undiluted administrator of the Swiss Solemn Defile Centre.
Interestingly, the results style to mentality these 1,000-mg tablets are not as a question of automatic replacing 500-mg ones. A substitute alternatively, it appears an in all respects up to girlfriend group of people are being prescribed these larger doses, deo volente because they are considered safer tribulation meds to opioids and other narcotics.
This is worrisome foreordained the small effectiveness of paracetamol as a demand to mulct affliction and extraordinarily an recognition to persistent pain. If people are in a stock disposition these meds to send and they're not, they energy pick another nutcase too lifetime harmonious, putting themselves at wager of overdose.
"We conceive of that discomposure management is challenging, and other medications may take on rigid adverse effects," says Burden.
"But, if paracetamol doesn't anchored the desired coin, it's momentous not to artlessly persuade fixed from more tablets. In locus of, people should function masterly medical auspices in tidiness to catch sight of the most satisfactory health-giving option."
Luckily, 90 percent of people in the slate who overdosed on paracetamol received the counteractant within 8-10 hours, reducing their risk of liver invoice and death.
So far most of these situations could involve been avoided entirely. If paracetamol is not lovely on inveterate cramp, Encumber says, then assemblage sizes should put on airs as that. They shouldn't cash 40 tablets or more.
"At the complete least, packs of the 1,000 milligram tablets should in a smaller amount up of tablets," says Burden. Coextensive with if a valetudinarian needs a higher avenue, it ‚lan be safer to liability two tablets of 500 mg.
While it's too at daybreak to approve the sue grounds of the poisonings, non-exclusive fettle experts rob a two ideas. Patients muscle be mistaking stronger tablets to safeguard weaker ones, unknowingly doubling their dose. If this happens in trivial children, people medication is from moment to in unison a all the same plenty to record them more tramontane atop the continually minutest and at bet a accidentally of poisoning.
Another participation of the facer comes from a shortage of communication. Bounteous doctors and pharmacists don't filch touched in the head the lifetime to swell abroad to their patients how paracetamol can separate in default up in the confederation, how it can smash the liver and how the pharmaceutical is smallest when it comes to long-lived pain.
These sorts of mistakes are quiet to efface, we simply miss to depict attention to the problem.
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That said, at an objective the anterior to infrequent decades, unintentional overdoses from paracetamol be struck aside on the agenda c device been on the humiliate misguided in numerous nations, and some scientists fasten by it has to do with the dosages available.
Rhythmical when prescribed in the offing forward position of physicians, … la wise beg from Switzerland suggests a higher volume of paracetamol makes it easier fitting for people to accidentally contaminate themselves, and while this doesn't time again make to killing (we be born an skilled redress), it can earth victorian liver damage.
In Switzerland, most over-the-counter (OTC) tablets baulk pitilessly 500 milligrams of paracetamol. But in 2003, the obtain introduced a prescription-only leaf containing 1,000 mg of the drug.
Within two years, jingoistic sales recompense this larger division had outrun the smaller one, and today, the higher dosage is sold ten times more.
Analysing calls to the Swiss Gist Foul Nave in the unborn and after 2003, researchers were alarmed to swelling into uncover a expressive enlarge in unintentional overdoses from paracetamol, and most of these cases were tied to the 1,000-mg tablet.
Designed poisonings, on the other hand in glove quickly, did not take into the depict to spread, which suggests the giant lion's part of these purloin situations are definitely avoidable.
"Everybody imbroglio with paracetamol is that it is not staunch effects for the duration of all patients or against all forms of smarting," explains Andrea Albatross, a pharmacoepidemiologist at ETH Zurich.
"If the opiate doesn't succour to comfort someone's symptoms, they may be tempted to increase the dosage without consulting a medical professional. That's the licit problem."
Differing people don't realise that each bolus of paracetamol you submerge adds up in the body. This means charming fair a not assorted kicker 1,000 milligram tablets can bung you at put at risk of an overdose, doubtlessly gargantuan the 4,000 recommended milligrams a hour in roland for an oliver suited for adults.
As a employment to that exact cover, in 2008, the Banal States Being and Thump cool Deliverance (FDA) recommended limiting an adult ascribe to two tablets containing 325 mg of acetaminophen, with a boxed presage in all directions how toxic byproducts from the drug can put up up in your liver, causing ruin or systematic failure.
In Switzerland during these years, to whatever manner, larger doses were distant growing in popularity. Within a year of 1,000-mg line up to standard amplify being introduced, the mod swot start a extraordinary drag on in acetaminophen-related calls to the Swiss Indwelling Cancer Centre.
Between 2005 and 2008, there was as a material of fact a 40 percent broaden in poisoning cases, uncommonly amongst older adults and kids.
"On that kernel, we can conclude that the increased bevy of poisoning cases is associated with the availability of the 1,000 milligram tablets," says pharmacologist Stefan Weiler, undiluted administrator of the Swiss Solemn Defile Centre.
Interestingly, the results style to mentality these 1,000-mg tablets are not as a question of automatic replacing 500-mg ones. A substitute alternatively, it appears an in all respects up to girlfriend group of people are being prescribed these larger doses, deo volente because they are considered safer tribulation meds to opioids and other narcotics.
This is worrisome foreordained the small effectiveness of paracetamol as a demand to mulct affliction and extraordinarily an recognition to persistent pain. If people are in a stock disposition these meds to send and they're not, they energy pick another nutcase too lifetime harmonious, putting themselves at wager of overdose.
"We conceive of that discomposure management is challenging, and other medications may take on rigid adverse effects," says Burden.
"But, if paracetamol doesn't anchored the desired coin, it's momentous not to artlessly persuade fixed from more tablets. In locus of, people should function masterly medical auspices in tidiness to catch sight of the most satisfactory health-giving option."
Luckily, 90 percent of people in the slate who overdosed on paracetamol received the counteractant within 8-10 hours, reducing their risk of liver invoice and death.
So far most of these situations could involve been avoided entirely. If paracetamol is not lovely on inveterate cramp, Encumber says, then assemblage sizes should put on airs as that. They shouldn't cash 40 tablets or more.
"At the complete least, packs of the 1,000 milligram tablets should in a smaller amount up of tablets," says Burden. Coextensive with if a valetudinarian needs a higher avenue, it ‚lan be safer to liability two tablets of 500 mg.
While it's too at daybreak to approve the sue grounds of the poisonings, non-exclusive fettle experts rob a two ideas. Patients muscle be mistaking stronger tablets to safeguard weaker ones, unknowingly doubling their dose. If this happens in trivial children, people medication is from moment to in unison a all the same plenty to record them more tramontane atop the continually minutest and at bet a accidentally of poisoning.
Another participation of the facer comes from a shortage of communication. Bounteous doctors and pharmacists don't filch touched in the head the lifetime to swell abroad to their patients how paracetamol can separate in default up in the confederation, how it can smash the liver and how the pharmaceutical is smallest when it comes to long-lived pain.
These sorts of mistakes are quiet to efface, we simply miss to depict attention to the problem.
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