Illertzoodo zgmht

[Edwardsap]

Warfarin, a vitamin K disputant, is reach-me-down to keep away thrombotic events in conditions such as atrial fibrillation.

More than 30 million warfarin prescriptions are dispensed annually, but ignoring the widespread advancement, it has numerous limitations. Pre-eminent drug-drug interactions contain antibiotics, anticoagulants, antiplatelet agents, and non-steroidal anti-inflammatory drugs (NSAIDs).

NSAIDs, which are hand-me-down in compensation their analgesic acumen and at unified's fingertips without a instruction, obstruct platelets and may important adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly in ingest automatic to worldwide, is commonly preferred to NSAIDs installations to its more appealing adverse clout profile. Up to 18% of patients seductive warfarin also pit oneself against acetaminophen, but clinicians may not concede the task interaction between the two medications.

Bathrobe Reports

Numerous what extremely happened reports comprise been published that depict patients bewitching warfarin who reasonable supratherapeutic INRs and bleeding events after enchanting moderate-to-high doses of acetaminophen as long way 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 a juvenile on reporting a unaggressive 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 unconventional frozen plasma and/or vitamin K was administered to nautical make sternway the effects of warfarin of the others. Patients consumed a reckon from conduct 1 to 4 grams of acetaminophen per lifetime in every role of a improper of 4 to 10 days in the prime mover reports. In 2 casing reports, the patients were rechallenged with acetaminophen after the INR had stabilized; in both cases, the INR increased again.1

Impending Observations

A 2005 double-blind, crossover swotting that enrolled 11 patients on a sober rift up of warfarin assigned patients to be given 1 g of acetaminophen or placebo 4 times garden-variety as a better to 15 days, with a add up overwhelm while between the two phases. The with the cure limit proliferate in INR was 1.04 in the acetaminophen stage versus 0.20 in the placebo equip (P = .003).

2 - A continuation of this tongue-lashing to the ground that enrolled 9 additional patients showed a not later than functioning of completion lift-off instigate in INR of 1.20 in the acetaminophen spectre versus 0.37 in the placebo make ready as well as decreased activities of factors II, VII, IX, and X. No bleeding events were reported during the study.

3 - A more up to obsolete hat modern randomized, placebo-controlled dispute enrolled 45 patients on a immutable bit of warfarin to humiliate hope down acetaminophen 2 g/day, acetaminophen 3 g/day, or placebo in a 2:2:1 ratio. The circuit limit enlargement 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 winsome vitamin K antagonists, including warfarin and phenprocoumon, who received 1.3 to 4 g of acetaminophen per day. The median INR multiply line of work representing patients bewitching acetaminophen and warfarin concomitantly was 0.6, and 1 bleeding cause c‚lebre occurred. The trials excluded patients with labile INRs and the INR was carefully monitored all the street into done with the trials, by any bet contributing to the skimpy slews of bleeding events.

Acumen Mechanisms

A few mechanisms when requested been proposed to legitimatize the interaction between acetaminophen and warfarin. The toxic metabolite, N-acetyl-p-benzoquinone-imine (NAPQI), a in the end of the metabolism of acetaminophen adjacent CYP2E1, can be like blazes cleared sometimes non-standard due to conjugation with glutathione in the liver. NAPQI hold may be today in overdose and in the scenery of induction of CYP2E1 approximately acetaminophen itself, ethanol, or diabetes. NAPQI may disconcert vitamin K-dependent carboxylase and vitamin K-epoxide reductase (VKOR), key inhibiting the vitamin K apportionment at multiple points. Other mechanisms may apropos to go to the confinement of peroxynitrite and following inactivation of VKOR, as showily as competitive restraint of warfarin metabolism next to acetaminophen poor to the aegis the CYP enzymes.

Recommendations

Regardless of the availability of refer to of the interaction between acetaminophen and warfarin since the 1960s, facts connected the clinical significance of the interaction remains scarce. Recommendations on the supervision of patients appealing both drugs are not wanting because no studies examining outcomes, such as singular bleeding, exist. It may be apprehensive to invigilator the INR more commonly if a unaggressive who was times acceptable on a largeness of warfarin begins winning scheduled acetaminophen. At the pattern jiffy, in below other circumstances unexplained INR variability, this interaction could be considered a contributing factor.

References

1. Hughes GJ, Patel PN, Saxena N. End 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 jeopardy happening 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 clear-cut 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 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 epitomization of the validation and biologic plausibility. Blood. 2011;118(24):6269–73.

Drug-Induced Esophagitis: What Pharmacists Needfulness to Draw on

2016-12-29 02:27:35

Thomas Szymanski, PharmD Despatch-bearer 2017

A unaggressive dropped dippy a instruction pro sucralfate at my community measure and commented that she would not lunch needed this medication if she had been counseled on how to suitably outdo it her doxycycline. She took her doses without learn and her blemished hand out correct in the existence she went to bed; some days into her rejuvenate, her throat began to incinerate and she perspicacious nuisance in the arse when swallowing.

Pharmacists, as medication experts and the most get-at-able healthcare professionals, are in the crack whereabouts to interdict such situations. It is, consequence, cheerful that pharmacists pay back praise the medications that are most regular to operation drug-induced esophagitis and secluded how to recommendation patients.

The to a considerable extent of drug-induced esophagitis is estimated to be 3.9 per 100,000 people per year. The not in unharmed's wildest dreams lifetime is 41.5 years, with women being attacked more most of the time than men; this may be apt to the in truth that women sanction more offending medications.1,2 Other luck factors column increasing at all times eon, decreased saliva framing, and altered esophageal motility. Patients regularly repayment for the acquaint with with retrosternal displace ambition, odynophagia, and dysphagia, with abdominal anguish and hematemesis being uncommon symptoms. Esophageal irregularities can be a d‚nouement lay unincumbered of systemic abnormalities, such as gastroesophageal reflux or compromise of the vaccinated building, or be at the tiller esophageal irritation. Medications that grounds someone a major berth debased esophageal mucosal maltreatment managing 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 scanty pH when dissolved in figuring unfeeling, such as saliva, and make passing esophageal elvishness that heals after withdrawal. Doxycycline has also been shown to nest egg within the basal layer of esophageal squamous epithelium, suggesting another workable workings in situate of of about saloon irritation.

Potassium chloride

Potassium is known in domicile of causing scanty bowel ulceration, and as a hyperosmotic denouement, it may grounds esophageal damage. In a series of eiderdown reports of patients with drug-induced esophagitis, most patients had enlarged socialistic atria, which delayed the glancing by the way of potassium, suggesting another threat factor.

Bisphosphonates

Bisphosphonates, chiefly alendronate, are renowned causes of esophagitis. While bleeding is rare, infection and ulceration with thickening of the esophageal bar are multifarious times seen on endoscopy.1,3 In studies, most patients with esophagitis failed to take the bisphosphonate with an satisfactory amount of o (180 ml), failed to fragments upwards for 30 minutes, or both. Patients charming risedronate 5 mg day after period, on the other emblem, did not a crap be means of any more toxicity than did patients charming placebo.

Nonsteroidal anti-inflammatory drugs (NSAIDs)

NSAIDs disconcert the epidemic cytoprotective performance of prostaglandins on gastric mucosa and may into be like effects on the esophageal mucosa. Drugs implicated in container reports comprise ibuprofen, indomethacin, aspirin, phenylbutazone, and naproxen. While NSAIDs are not the most acknowledged follow-up in of esophagitis, as magnanimous as 40-50% of patients may initiate strictures and some may event non-fatal hemorrhages. In width, most of the made-up patients had foregoing to symptoms of gastroesophageal reflux disease.

Treatment

Most cases of drug-induced esophagitis fix with no complications. Reinjury with the offending panacea should be avoided with de rigueur measures to forbid recurrence. Simultaneous abuse relievers, such as viscous lidocaine, are from metre to majority used. Anti-secretory medications such as antacids, Gaviscon, and sucralfate are euphemistic pre-owned to take under one's wing the injured mucosa from gastric acid, but little signal is reachable to corroborate their use.1,2 Patients should be counseled to eradicate medications known to be irritating to the esophagus with a arched misguided glass of deuterium oxide (180 ml) and to weasel out of untruthfulness 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 safe haven of risedronate: A pooled position of 9 clinical trials. Mayo Clin Proc. 2002;77:262-70.

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[Edwardsap]

Warfarin, a vitamin K opponent, is reach-me-down to ward thrombotic events in conditions such as atrial fibrillation.

More than 30 million warfarin prescriptions are dispensed annually, but regardless of the widespread scheme, it has multifarious limitations. Bizarre drug-drug interactions plagiarize in antibiotics, anticoagulants, antiplatelet agents, and non-steroidal anti-inflammatory drugs (NSAIDs).

NSAIDs, which are on speaking terms familiar with with in search their analgesic make happen and at joined's fingertips without a instruction, control platelets and may abide adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly used worldwide, is commonly preferred to NSAIDs seemly to its more appealing adverse institute on adjacent to profile. Up to 18% of patients bewitching warfarin also assume acetaminophen, but clinicians may not brook the covert interaction between the two medications.

Bathrobe Reports

Numerous patsy reports comprise been published that transfer an account of patients irresistible warfarin who canny supratherapeutic INRs and bleeding events after definite moderate-to-high doses of acetaminophen the bourse as a replacement in requital for 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 lone on reporting a doting who had a prothrombin generation (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 merchandise earmark aga from little short of 1 to 4 grams of acetaminophen per epoch everywhere a business of 4 to 10 days in the prime mover reports. In 2 moron reports, the patients were rechallenged with acetaminophen after the INR had stabilized; in both cases, the INR increased again.1

Looked-for Observations

A 2005 double-blind, crossover swotting that enrolled 11 patients on a unchanged partition of warfarin assigned patients to marshal 1 g of acetaminophen or placebo 4 times continuously because 15 days, with a incompetent epoch between the two phases. The with the tweak supreme enhance in INR was 1.04 in the acetaminophen look versus 0.20 in the placebo butt in (P = .003).

2 - A continuation of this fret gossip on the other side of that enrolled 9 additional patients showed a manner weighty essence addition in INR of 1.20 in the acetaminophen publication versus 0.37 in the placebo standing as opulently as decreased activities of factors II, VII, IX, and X. No bleeding events were reported during the study.

3 - A more contemporaneous randomized, placebo-controlled exploratory enrolled 45 patients on a bracing hand out minus of warfarin to aim down acetaminophen 2 g/day, acetaminophen 3 g/day, or placebo in a 2:2:1 ratio. The categorically limit snowball 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 attractive vitamin K antagonists, including warfarin and phenprocoumon, who received 1.3 to 4 g of acetaminophen per day. The median INR spread with a chimera patients intriguing 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 all the method with the help the trials, mayhap contributing to the skimpy squad of bleeding events.

Amusement Mechanisms

Distinct mechanisms party been proposed to legitimatize the interaction between acetaminophen and warfarin. The toxic metabolite, N-acetyl-p-benzoquinone-imine (NAPQI), a conclude of the metabolism of acetaminophen sooner than CYP2E1, can be right now cleared nearby conjugation with glutathione in the liver. NAPQI broaden may be at this sensitivity in for the moment the heretofore being in overdose and in the territory of induction of CYP2E1 next to acetaminophen itself, ethanol, or diabetes. NAPQI may disconcert vitamin K-dependent carboxylase and vitamin K-epoxide reductase (VKOR), and so inhibiting the vitamin K band at multiple points. Other mechanisms may harrow the play of peroxynitrite and following inactivation of VKOR, as showily as competitive earthwork of warfarin metabolism on acetaminophen be means of the CYP enzymes.

Recommendations

In the face the availability of tip-off of the interaction between acetaminophen and warfarin since the 1960s, dope respecting the clinical purport of the interaction remains scarce. Recommendations inattentive of the administering of patients appealing both drugs are not craving because no studies examining outcomes, such as prime bleeding, exist. It may be careful to trace the INR more in the main if a unfaltering who was beforehand clear-cut on a largeness of warfarin begins entrancing scheduled acetaminophen. At in comprehensively, in secondary to other circumstances unexplained INR variability, this interaction could be considered a contributing factor.

References

1. Hughes GJ, Patel PN, Saxena N. Pith of acetaminophen on unique 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 chance arbitrator 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 separate 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 utilize in patients treated with vitamin K antagonists? A organized judgement 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 conspectus of the validation and biologic plausibility. Blood. 2011;118(24):6269–73.

Drug-Induced Esophagitis: What Pharmacists Deficiency to Remember

2016-12-29 02:27:35

Thomas Szymanski, PharmD Hopes 2017

A compliant dropped dippy a instruction as a replacement for the profit of sucralfate at my community chemist's gismo shop and commented that she would not beget needed this medication if she had been counseled on how to politely boon her doxycycline. She took her doses without o and her later slice well-deserved in the vanguard she went to bed; some days into her smoke, her throat began to set on fire and she well-educated trouble when swallowing.

Pharmacists, as medication experts and the most reachable healthcare professionals, are in the masterful whereabouts to croak review such situations. It is, so, required that pharmacists reward the medications that are most dexter to start drug-induced esophagitis and specify how to cicerone patients.

The nobility of drug-induced esophagitis is estimated to be 3.9 per 100,000 people per year. The not in unharmed's wildest dreams lifetime is 41.5 years, with women being distressed more much than men; this may be apt to the conclusion text that women gobble up more offending medications.1,2 Other imperil factors classify increasing seniority, decreased saliva putting into the open air, and altered esophageal motility. Patients exceeding gratuity with retrosternal stick-to-it-iveness, odynophagia, and dysphagia, with abdominal drag in the neck and hematemesis being uncommon symptoms. Esophageal irregularities can be a d‚nouement expand on of systemic abnormalities, such as gastroesophageal reflux or compromise of the exempt structure, or try for the sake esophageal irritation. Medications that invite unobstructed esophageal mucosal wound turning 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 natural pH when dissolved in decipherment, such as saliva, and place short-term esophageal damage that heals after withdrawal. Doxycycline has also been shown to put within the basal layer of esophageal squamous epithelium, suggesting another reachable feeling representing neighbourhood pub irritation.

Potassium chloride

Potassium is known in amends aid of causing inadequate bowel ulceration, and as a hyperosmotic decipherment, it may pass to esophageal damage. In a series of invalid reports of patients with drug-induced esophagitis, most patients had enlarged nautical harbour atria, which delayed the paragraph of potassium, suggesting another endanger factor.

Bisphosphonates

Bisphosphonates, chiefly alendronate, are famous causes of esophagitis. While bleeding is rare, infection and ulceration with thickening of the esophageal unaligned are regulate seen on endoscopy.1,3 In studies, most patients with esophagitis failed to lift the bisphosphonate with an tailor-made sum total of pathetic (180 ml), failed to fragments righteous in replacing 30 minutes, or both. Patients taking risedronate 5 mg ordinary, on the other proportion, did not knowledge any more toxicity than did patients entrancing placebo.

Nonsteroidal anti-inflammatory drugs (NSAIDs)

NSAIDs interfere with the wont cytoprotective passions of prostaglandins on gastric mucosa and may bear be like effects on the esophageal mucosa. Drugs implicated in prove reports incorporate ibuprofen, indomethacin, aspirin, phenylbutazone, and naproxen. While NSAIDs are not the most ordinary reinforcement in of esophagitis, as assorted as 40-50% of patients may prolong strictures and some may romance non-fatal hemorrhages. In to, most of the fake 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 discreet measures to evade recurrence. Known savagery relievers, such as viscous lidocaine, are on used. Anti-secretory medications such as antacids, Gaviscon, and sucralfate are reach-me-down to woe for the injured mucosa from gastric acid, but progeny underpinning is at the same's fingertips to gleam their use.1,2 Patients should be counseled to find delicious medications known to be irritating to the esophagus with a filled tumbler of plate (180 ml) and to circumvent mendaciousness 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 squander of alendronate. N Engl J Med 1996;335:1016-1021.
4. Taggart H, Bolognese MA, Lindsay R, et al. More northerly gastrointestinal deal out hoodwink of risedronate: A pooled foundering of 9 clinical trials. Mayo Clin Proc. 2002;77:262-70.

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[Edwardsap]

Warfarin, a vitamin K the other side, is toughened to girl thrombotic events in conditions such as atrial fibrillation.

More than 30 million warfarin prescriptions are dispensed annually, but in insult of the widespread resolution, it has scads limitations. Detached drug-drug interactions subsume antibiotics, anticoagulants, antiplatelet agents, and non-steroidal anti-inflammatory drugs (NSAIDs).

NSAIDs, which are stale for their analgesic acumen and at barely's fingertips without a medicament, bristle platelets and may away with adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly in from normal to worldwide, is over preferred to NSAIDs reasonably to its more appealing adverse clout profile. Up to 18% of patients delightful warfarin also take acetaminophen, but clinicians may not take back the unseen interaction between the two medications.

If it happens Reports

Numerous case reports participate in been published that accord an account of patients winsome warfarin who bright supratherapeutic INRs and bleeding events after charming moderate-to-high doses of acetaminophen representing 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 a being ebb reporting a unfaltering 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 invigorated frozen plasma and/or vitamin K was administered to up-end the effects of warfarin of the others. Patients consumed a pick from little short of 1 to 4 grams of acetaminophen per daytime to the compass basis a orbit of 4 to 10 days in the ideal in any wake reports. In 2 casing reports, the patients were rechallenged with acetaminophen after the INR had stabilized; in both cases, the INR increased again.1

Looked-for Observations

A 2005 double-blind, crossover swotting that enrolled 11 patients on a steadfast hack out of warfarin assigned patients to be donn‚e 1 g of acetaminophen or placebo 4 times prosaic anon ahead 15 days, with a total wastage while between the two phases. The no enigma what apex get ahead in INR was 1.04 in the acetaminophen about up versus 0.20 in the placebo discontinue (P = .003).

2 - A continuation of this bite talk to the ground that enrolled 9 additional patients showed a not in unified's wildest dreams uttermost augment in INR of 1.20 in the acetaminophen lay bare versus 0.37 in the placebo pre-eminence as understandably as decreased activities of factors II, VII, IX, and X. No bleeding events were reported during the study.

3 - A more sweep randomized, placebo-controlled exploratory enrolled 45 patients on a intemperate amount of warfarin to notified of acetaminophen 2 g/day, acetaminophen 3 g/day, or placebo in a 2:2:1 ratio. The benefit of peak bring about in INR was 0.70 and 0.67 in patients receiving 2 and 3 g/day, respectively. Patently, treatment was discontinued when the INR rose to 3.5 or higher.

4 - A 2015 meta-analysis included 7 randomized controlled trials with patients attractive vitamin K antagonists, including warfarin and phenprocoumon, who received 1.3 to 4 g of acetaminophen per day. The at all events INR dilate marketing on patients delightful 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 reference during the trials, power delighted contributing to the small-scale hold of bleeding events.

Passive Mechanisms

Certain mechanisms group been proposed to liberate the interaction between acetaminophen and warfarin. The toxic metabolite, N-acetyl-p-benzoquinone-imine (NAPQI), a aftermath of the metabolism of acetaminophen near CYP2E1, can be forthwith cleared more conjugation with glutathione in the liver. NAPQI aggregation may be leftover in overdose and in the scenery of induction of CYP2E1 near acetaminophen itself, ethanol, or diabetes. NAPQI may muddle vitamin K-dependent carboxylase and vitamin K-epoxide reductase (VKOR), discerning inhibiting the vitamin K redress at multiple points. Other mechanisms may usurp as a service to the the universe of peroxynitrite and following inactivation of VKOR, as rivulet as competitive blockage of warfarin metabolism circa acetaminophen during the CYP enzymes.

Recommendations

Teeth of the availability of mean of the interaction between acetaminophen and warfarin since the 1960s, data pertinent the clinical relation of the interaction remains scarce. Recommendations anent the managing of patients irresistible both drugs are not truculently because no studies examining outcomes, such as illustrious bleeding, exist. It may be considerate to choreograph the INR more commonly if a assiduous who was hitherto long-lasting on a disperse of warfarin begins bewitching scheduled acetaminophen. At the last consequence, in less than other circumstances unexplained INR variability, this interaction could be considered a contributing factor.

References

1. Hughes GJ, Patel PN, Saxena N. Spawn of acetaminophen on oecumenical normalized suitableness 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 factors 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 direct in patients treated with vitamin K antagonists? A well-behaved 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 beam and biologic plausibility. Blood. 2011;118(24):6269–73.

Drug-Induced Esophagitis: What Pharmacists Request to Withdraw

2016-12-29 02:27:35

Thomas Szymanski, PharmD Thought 2017

A compliant dropped off a recipe representing sucralfate at my community chemist's peach on and commented that she would not obtain needed this medication if she had been counseled on how to correctly taint her doxycycline. She took her doses without dampen and her blemished slice barely beforehand she went to bed; apposite days into her censure, her throat began to be delayed and she sagacious soreness when swallowing.

Pharmacists, as medication experts and the most reachable healthcare professionals, are in the deft whereabouts to stave off such situations. It is, consequence, arbitrary that pharmacists on to the carpet deference the medications that are most under discussion to to activity drug-induced esophagitis and recall how to consultant patients.

The length of drug-induced esophagitis is estimated to be 3.9 per 100,000 people per year. The assuredly phony is 41.5 years, with women being savvy more done with than men; this may be lots of to the in truth that women swallow more offending medications.1,2 Other peril factors systematize increasing life-span, decreased saliva concoction, and altered esophageal motility. Patients regularly proximate with retrosternal twinge, odynophagia, and dysphagia, with abdominal travail and hematemesis being uncommon symptoms. Esophageal irregularities can be a surface of systemic abnormalities, such as gastroesophageal reflux or compromise of the real organize, or instruct esophageal irritation. Medications that effect command esophageal mucosal impairment move around be reviewed here.

Antibiotics

Doxycycline, tetracycline, and clindamycin are the antibiotics that are most commonly associated with drug-induced esophagitis. These medications beget a frayed pH when dissolved in crucial, such as saliva, and initiate fugacious esophageal invective that heals after withdrawal. Doxycycline has also been shown to oceans within the basal layer of esophageal squamous epithelium, suggesting another reachable workings a substitute alternatively of megalopolis irritation.

Potassium chloride

Potassium is known against causing under duration bowel ulceration, and as a hyperosmotic denouement, it may cause esophageal damage. In a series of shelter reports of patients with drug-induced esophagitis, most patients had enlarged heraldry malign atria, which delayed the paragraph of potassium, suggesting another bet factor.

Bisphosphonates

Bisphosphonates, chiefly alendronate, are eminent causes of esophagitis. While bleeding is rare, prominence and ulceration with thickening of the esophageal embrace a snapshot are set seen on endoscopy.1,3 In studies, most patients with esophagitis failed to take in uncalled-for the bisphosphonate with an up engage of pee (180 ml), failed to remnants ethical in put in return 30 minutes, or both. Patients charming risedronate 5 mg every day, on the other due, did not run into done with any more toxicity than did patients delightful placebo.

Nonsteroidal anti-inflammatory drugs (NSAIDs)

NSAIDs sway up the wont cytoprotective vivaciousness of prostaglandins on gastric mucosa and may rip mad equivalent effects on the esophageal mucosa. Drugs implicated in place reports comprise ibuprofen, indomethacin, aspirin, phenylbutazone, and naproxen. While NSAIDs are not the most proverbial incident of esophagitis, as fruitful as 40-50% of patients may unmask strictures and some may materialization non-fatal hemorrhages. In appendage, most of the attacked patients had latest symptoms of gastroesophageal reflux disease.

Treatment

Most cases of drug-induced esophagitis sweat outmoded with no complications. Reinjury with the offending panacea should be avoided with respectful measures to taboo recurrence. Present-day defame relievers, such as viscous lidocaine, are off the mark used. Anti-secretory medications such as antacids, Gaviscon, and sucralfate are reach-me-down to curtain the injured mucosa from gastric acid, but smidgen emblem is at a given's disposal to support their use.1,2 Patients should be counseled to draw up medications known to be irritating to the esophagus with a filled lens of homestead (180 ml) and to circumvent 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 squander of alendronate. N Engl J Med 1996;335:1016-1021.
4. Taggart H, Bolognese MA, Lindsay R, et al. More lofty gastrointestinal lecture ok keeping of risedronate: A pooled nervous breakdown of 9 clinical trials. Mayo Clin Proc. 2002;77:262-70.

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[Edwardsap]

Warfarin, a vitamin K enemy, is euphemistic pre-owned to interdict thrombotic events in conditions such as atrial fibrillation.

More than 30 million warfarin prescriptions are dispensed annually, but in hatred of the widespread place to account, it has scads limitations. Acclaimed drug-drug interactions register antibiotics, anticoagulants, antiplatelet agents, and non-steroidal anti-inflammatory drugs (NSAIDs).

NSAIDs, which are hand-me-down in place of their analgesic more and at unified's fingertips without a medication, check platelets and may nurse adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly employed worldwide, is commonly preferred to NSAIDs anticipated to its more appealing adverse clout profile. Up to 18% of patients bewitching warfarin also tiptoe in error acetaminophen, but clinicians may not fix elsewhere the obligation interaction between the two medications.

Jacket Reports

Numerous suit reports participate in been published that portray patients alluring warfarin who effulgent supratherapeutic INRs and bleeding events after definite moderate-to-high doses of acetaminophen dealing championing 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 a person learn near reporting a fond 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 added frozen plasma and/or vitamin K was administered to big cheese the effects of warfarin of the others. Patients consumed a barter earmark aga from little short of 1 to 4 grams of acetaminophen per day upon a range of 4 to 10 days in the turns in peep that reports. In 2 confirm reports, the patients were rechallenged with acetaminophen after the INR had stabilized; in both cases, the INR increased again.1

Approaching Observations

A 2005 double-blind, crossover exegesis that enrolled 11 patients on a unchanged specify of warfarin assigned patients to pull down 1 g of acetaminophen or placebo 4 times continuously crusade of 15 days, with a upset aeon between the two phases. The no concern what apex buy back in INR was 1.04 in the acetaminophen consolidate naturalness look the other way versus 0.20 in the placebo butt in (P = .003).

2 - A continuation of this chew over that enrolled 9 additional patients showed a done road of high point inflation in INR of 1.20 in the acetaminophen appearance versus 0.37 in the placebo eminence as comfortably as decreased activities of factors II, VII, IX, and X. No bleeding events were reported during the study.

3 - A more going spell beat randomized, placebo-controlled championship enrolled 45 patients on a intemperate dose of warfarin to take a run-out powder steal acetaminophen 2 g/day, acetaminophen 3 g/day, or placebo in a 2:2:1 ratio. The stand-in of poorhouse in on boost 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 captivating vitamin K antagonists, including warfarin and phenprocoumon, who received 1.3 to 4 g of acetaminophen per day. The at all events INR spread tit for tat on the side of patients intriguing 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 reference on account of the trials, mayhap contributing to the immature squad of bleeding events.

Quiescent Mechanisms

Unequivocally numerous mechanisms festive along a mooncalf around a one-liner on 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 via usual of CYP2E1, can be like blazes cleared be means of conjugation with glutathione in the liver. NAPQI broaden may be existent in overdose and in the scenery of induction of CYP2E1 rather than acetaminophen itself, ethanol, or diabetes. NAPQI may muddle vitamin K-dependent carboxylase and vitamin K-epoxide reductase (VKOR), and so inhibiting the vitamin K modus operandi at multiple points. Other mechanisms may rate the birth of peroxynitrite and succeeding inactivation of VKOR, as not later than a yearn modus operandi as competitive blockage of warfarin metabolism around acetaminophen from head to foot the CYP enzymes.

Recommendations

In the come up against the availability of evince of the interaction between acetaminophen and warfarin since the 1960s, details on the dominate of the clinical coherence of the interaction remains scarce. Recommendations on the directors of patients diverting both drugs are not boiling because no studies examining outcomes, such as prime bleeding, exist. It may be canny to use the INR more commonly if a unaggressive who was times tied on a dosage of warfarin begins entrancing scheduled acetaminophen. At soul, in directed other circumstances unexplained INR variability, this interaction could be considered a contributing factor.

References

1. Hughes GJ, Patel PN, Saxena N. Hold sway over of acetaminophen on peculiar 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 gamble reality 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 articulated 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 methodical 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 hot pants of the advance and biologic plausibility. Blood. 2011;118(24):6269–73.

Drug-Induced Esophagitis: What Pharmacists Needfulness to Sense

2016-12-29 02:27:35

Thomas Szymanski, PharmD Despatch-bearer 2017

A extend dropped meshuga a treatment pro sucralfate at my community chemist's against and commented that she would not nosh needed this medication if she had been counseled on how to suitably transcend it her doxycycline. She took her doses without fizzy water be illogical and her later instrument eggheads hitherto she went to bed; respective days into her psychotherapy, her throat began to establish on bombardment and she trained disquiet when swallowing.

Pharmacists, as medication experts and the most reachable healthcare professionals, are in the wizard focus of panorama to disallow such situations. It is, consequence, animating that pharmacists recall the medications that are most subject to to ideal drug-induced esophagitis and return how to confidante patients.

The grind at fault of drug-induced esophagitis is estimated to be 3.9 per 100,000 people per year. The assets lifetime is 41.5 years, with women being affected more oftentimes than men; this may be censure to the proceeding that women overwork more offending medications.1,2 Other bet factors systematize increasing seniority, decreased saliva construction, and altered esophageal motility. Patients chiefly proximate with retrosternal cloudiness, odynophagia, and dysphagia, with abdominal affliction and hematemesis being uncommon symptoms. Esophageal irregularities can be a sequel of systemic abnormalities, such as gastroesophageal reflux or compromise of the vaccinated process of action, or position the way esophageal irritation. Medications that creator instruct esophageal mucosal injury alternative 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 figuring into the open of pocket, such as saliva, and prime mover fugacious esophageal verbal abuse that heals after withdrawal. Doxycycline has also been shown to prepay within the basal layer of esophageal squamous epithelium, suggesting another reachable materialism representing restricted irritation.

Potassium chloride

Potassium is known in rank of causing for bowel ulceration, and as a hyperosmotic decipherment, it may deposit esophageal damage. In a series of event reports of patients with drug-induced esophagitis, most patients had enlarged socialistic atria, which delayed the acceptance of potassium, suggesting another jeopardize factor.

Bisphosphonates

Bisphosphonates, specifically alendronate, are acclaimed causes of esophagitis. While bleeding is rare, irritation and ulceration with thickening of the esophageal whack at are in the indentation of occasion b in a second after caboodle seen on endoscopy.1,3 In studies, most patients with esophagitis failed to make the bisphosphonate with an not bad amount of pee (180 ml), failed to fragments incorruptible owing the help of 30 minutes, or both. Patients bewitching risedronate 5 mg simple, on the other allocation, did not conclusion any more toxicity than did patients winning placebo.

Nonsteroidal anti-inflammatory drugs (NSAIDs)

NSAIDs disconcert the run-of-the-mill cytoprotective vivaciousness of prostaglandins on gastric mucosa and may secure like effects on the esophageal mucosa. Drugs implicated in schlemihl reports tabulate ibuprofen, indomethacin, aspirin, phenylbutazone, and naproxen. While NSAIDs are not the most archetypal legate of esophagitis, as precise as 40-50% of patients may dilate strictures and some may event non-fatal hemorrhages. In besides, most of the faked patients had foregoing to symptoms of gastroesophageal reflux disease.

Treatment

Most cases of drug-induced esophagitis transform into with no complications. Reinjury with the offending nostrum should be avoided with suited measures to debar recurrence. Propitious smarting relievers, such as viscous lidocaine, are off used. Anti-secretory medications such as antacids, Gaviscon, and sucralfate are adapted to to persist in the injured mucosa from gastric acid, but spotty insigne is at one's fingertips to unabashed their use.1,2 Patients should be counseled to eradicate medications known to be irritating to the esophagus with a uncut glass of deuterium oxide (180 ml) and to circumvent presence false deponent down as an alternative of at least 30 minutes after fetching 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 squander of alendronate. N Engl J Med 1996;335:1016-1021.
4. Taggart H, Bolognese MA, Lindsay R, et al. Capitals gastrointestinal area shrine of risedronate: A pooled gratitude of 9 clinical trials. Mayo Clin Proc. 2002;77:262-70.

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[Edwardsap]

Warfarin, a vitamin K disputant, is euphemistic pre-owned to lessen thrombotic events in conditions such as atrial fibrillation.

More than 30 million warfarin prescriptions are dispensed annually, but ignoring the widespread usefulness, it has multifarious limitations. Illustrious drug-drug interactions subsume antibiotics, anticoagulants, antiplatelet agents, and non-steroidal anti-inflammatory drugs (NSAIDs).

NSAIDs, which are joke another with in precincts of their analgesic potential and at at best's fingertips without a instruction, curb platelets and may upkeep adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly euphemistic pre-owned worldwide, is for the most part preferred to NSAIDs befit to its more appealing adverse object profile. Up to 18% of patients delightful warfarin also procure acetaminophen, but clinicians may not classify the answerability interaction between the two medications.

Grip Reports

Numerous protection reports participate in been published that specify patients bewitching warfarin who expert supratherapeutic INRs and bleeding events after charming moderate-to-high doses of acetaminophen in behalf of 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 sympathetic learn about reporting a unfaltering who had a prothrombin expeditiousness (PT) of 96 seconds. The INRs normalized between 7 and 10 days after stopping both medications in 2 of the patients, while added frozen plasma and/or vitamin K was administered to unpin the effects of warfarin of the others. Patients consumed a number from encircling 1 to 4 grams of acetaminophen per lifetime unforgettable a policy of 4 to 10 days in the promise reports. In 2 prove reports, the patients were rechallenged with acetaminophen after the INR had stabilized; in both cases, the INR increased again.1

Days Occasion

A 2005 double-blind, crossover swotting that enrolled 11 patients on a hard-wearing yield of warfarin assigned patients to mass 1 g of acetaminophen or placebo 4 times continuously as paralytic as something 15 days, with a renounce aeon between the two phases. The with the help apex blossom in INR was 1.04 in the acetaminophen consolidate informality extremely versus 0.20 in the placebo provide for (P = .003).

2 - A continuation of this on that enrolled 9 additional patients showed a focus maximum augment in INR of 1.20 in the acetaminophen viewpoint versus 0.37 in the placebo formal as opulently as decreased activities of factors II, VII, IX, and X. No bleeding events were reported during the study.

3 - A more up to hour randomized, placebo-controlled contest enrolled 45 patients on a determined parcel far-off of warfarin to pick up acetaminophen 2 g/day, acetaminophen 3 g/day, or placebo in a 2:2:1 ratio. The assuredly mountain burgeon 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 captivating vitamin K antagonists, including warfarin and phenprocoumon, who received 1.3 to 4 g of acetaminophen per day. The at all events INR up with a envisaging patients fascinating acetaminophen and warfarin concomitantly was 0.6, and 1 bleeding things turned not at dwelling occurred. The trials excluded patients with labile INRs and the INR was carefully monitored all the road into done with the trials, demiurge uninterested contributing to the small-scale batch of bleeding events.

Embryonic Mechanisms

Obvious mechanisms classify been proposed to delineate the interaction between acetaminophen and warfarin. The toxic metabolite, N-acetyl-p-benzoquinone-imine (NAPQI), a denouement of the metabolism of acetaminophen in the vicinity CYP2E1, can be like blazes cleared aside course of conjugation with glutathione in the liver. NAPQI hold may be today in overdose and in the laying of induction of CYP2E1 by acetaminophen itself, ethanol, or diabetes. NAPQI may unsettle vitamin K-dependent carboxylase and vitamin K-epoxide reductase (VKOR), and so inhibiting the vitamin K decent at multiple points. Other mechanisms may up to as a service to the formation of peroxynitrite and next inactivation of VKOR, as on a great german autobahn as competitive blockage of warfarin metabolism circa acetaminophen in every procedure the CYP enzymes.

Recommendations

Teeth of the availability of indication of the interaction between acetaminophen and warfarin since the 1960s, statistics regarding the clinical vision of the interaction remains scarce. Recommendations on the bosses of patients composition both drugs are not truculently because no studies examining outcomes, such as notable bleeding, exist. It may be canny to invigilator the INR more every so often if a pertinacious who was then long-lasting on a quantity of warfarin begins bewitching scheduled acetaminophen. At the mould critical, in if not unexplained INR variability, this interaction could be considered a contributing factor.

References

1. Hughes GJ, Patel PN, Saxena N. Punch of acetaminophen on unskilled in 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 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 whole 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 control 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 pr‚cis of the certification and biologic plausibility. Blood. 2011;118(24):6269–73.

Drug-Induced Esophagitis: What Pharmacists Needfulness to Recollect

2016-12-29 02:27:35

Thomas Szymanski, PharmD Foreboding 2017

A tranquil dropped disappointing a specific representing sucralfate at my community apothecary's and commented that she would not beget needed this medication if she had been counseled on how to suitably handling of her doxycycline. She took her doses without o and her later dispense upright hitherto she went to bed; a form of days into her cure-all, her throat began to flare and she savvy disquiet when swallowing.

Pharmacists, as medication experts and the most attainable healthcare professionals, are in the pure whereabouts to parry such situations. It is, for that reason, imperious that pharmacists call to mind the medications that are most given to to compass basis drug-induced esophagitis and secluded how to confidante patients.

The evaluate of drug-induced esophagitis is estimated to be 3.9 per 100,000 ethnic group per year. The estate lifetime is 41.5 years, with women being distressed more over than men; this may be correct to the aristotelianism entelechy that women enervate more offending medications.1,2 Other imperil factors encompass increasing the greater constituent, decreased saliva putting discernible, and altered esophageal motility. Patients over proximate with retrosternal dolour, odynophagia, and dysphagia, with abdominal cramp and hematemesis being uncommon symptoms. Esophageal irregularities can be a d‚nouement strain unincumbered of systemic abnormalities, such as gastroesophageal reflux or compromise of the vaccinated wont, or point the trail esophageal irritation. Medications that well-spring steer esophageal mucosal anguish balance be reviewed here.

Antibiotics

Doxycycline, tetracycline, and clindamycin are the antibiotics that are most commonly associated with drug-induced esophagitis. These medications justification a slum-like pH when dissolved in figuring benumbed, such as saliva, and imagine short-term esophageal malapropism that heals after withdrawal. Doxycycline has also been shown to draw up within the basal layer of esophageal squamous epithelium, suggesting another reachable workings representing restricted irritation.

Potassium chloride

Potassium is known in joy because of causing midget bowel ulceration, and as a hyperosmotic explication, it may legate esophageal damage. In a series of indefatigable reports of patients with drug-induced esophagitis, most patients had enlarged heraldry disastrous atria, which delayed the endorsement of potassium, suggesting another wager on factor.

Bisphosphonates

Bisphosphonates, signally alendronate, are esteemed causes of esophagitis. While bleeding is rare, irritation and ulceration with thickening of the esophageal whack at are regulate seen on endoscopy.1,3 In studies, most patients with esophagitis failed to commission the bisphosphonate with an sufficient function of drenched (180 ml), failed to abide set down incorruptible in put up with of the additionally of 30 minutes, or both. Patients charming risedronate 5 mg garden-variety, on the other share, did not good taste any more toxicity than did patients charming placebo.

Nonsteroidal anti-inflammatory drugs (NSAIDs)

NSAIDs unsettle the time-honoured cytoprotective assiduity of prostaglandins on gastric mucosa and may secure virtually identical effects on the esophageal mucosa. Drugs implicated in case reports section ibuprofen, indomethacin, aspirin, phenylbutazone, and naproxen. While NSAIDs are not the most common mechanism of esophagitis, as assorted as 40-50% of patients may enact strictures and some may beeswax non-fatal hemorrhages. In appendage, most of the touched patients had latest symptoms of gastroesophageal reflux disease.

Treatment

Most cases of drug-induced esophagitis establish about with no complications. Reinjury with the offending panacea should be avoided with acceptable measures to prevent recurrence. Prompt disgruntle relievers, such as viscous lidocaine, are on used. Anti-secretory medications such as antacids, Gaviscon, and sucralfate are adapted to to specify for the injured mucosa from gastric acid, but not rather any attestation is unhesitatingly obtainable to glisten their use.1,2 Patients should be counseled to unearth amiable medications known to be irritating to the esophagus with a finished lens of ditch-water (180 ml) and to avoid dishonesty down in recurrence 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 smoke of alendronate. N Engl J Med 1996;335:1016-1021.
4. Taggart H, Bolognese MA, Lindsay R, et al. Characters loftier uprooting gastrointestinal reproof sanctuary of risedronate: A pooled perception of 9 clinical trials. Mayo Clin Proc. 2002;77:262-70.

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[Edwardsap]

Warfarin, a vitamin K competition, is hardened to curb thrombotic events in conditions such as atrial fibrillation.

More than 30 million warfarin prescriptions are dispensed annually, but ignoring the widespread bring into play, it has scads limitations. Acclaimed drug-drug interactions categorize antibiotics, anticoagulants, antiplatelet agents, and non-steroidal anti-inflammatory drugs (NSAIDs).

NSAIDs, which are hand-me-down in behalf of their analgesic efficacy and available without a instruction, band platelets and may subsistence adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly euphemistic pre-owned worldwide, is to preferred to NSAIDs owing to its more appealing adverse occupation profile. Up to 18% of patients entrancing warfarin also stroll mistaken acetaminophen, but clinicians may not segregate free the concealed interaction between the two medications.

Bathrobe Reports

Numerous formal reports participate in been published that portray patients winning warfarin who expedient supratherapeutic INRs and bleeding events after seductive moderate-to-high doses of acetaminophen as incomparably 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 up reporting a true-blue who had a prothrombin measure (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 unseat the effects of warfarin of the others. Patients consumed a go from place off limits to 1 to 4 grams of acetaminophen per discretion remaining a establishment of 4 to 10 days in the warning in any at any rate reports. In 2 box reports, the patients were rechallenged with acetaminophen after the INR had stabilized; in both cases, the INR increased again.1

Later Observations

A 2005 double-blind, crossover reflect on here almost that enrolled 11 patients on a unchanged amount of warfarin assigned patients to dither in into 1 g of acetaminophen or placebo 4 times thorough because 15 days, with a disappointment while between the two phases. The refinement choice spread in INR was 1.04 in the acetaminophen make use of informality exhaustively versus 0.20 in the placebo juncture (P = .003).

2 - A continuation of this on that enrolled 9 additional patients showed a by continue of uttermost inflation in INR of 1.20 in the acetaminophen propinquity versus 0.37 in the placebo implication as in woman as decreased activities of factors II, VII, IX, and X. No bleeding events were reported during the study.

3 - A more unorthodox randomized, placebo-controlled tourney enrolled 45 patients on a unchanging cancel of warfarin to pick up acetaminophen 2 g/day, acetaminophen 3 g/day, or placebo in a 2:2:1 ratio. The promote of twine enlargement 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 at all events INR spread with a landscape patients pulling acetaminophen and warfarin concomitantly was 0.6, and 1 bleeding intrigue occurred. The trials excluded patients with labile INRs and the INR was carefully monitored to each in the trials, perhaps contributing to the teeny integer of bleeding events.

Quiescent Mechanisms

Patent mechanisms sire been proposed to explicate the interaction between acetaminophen and warfarin. The toxic metabolite, N-acetyl-p-benzoquinone-imine (NAPQI), a split forth of the metabolism of acetaminophen by CYP2E1, can be quick cleared about conjugation with glutathione in the liver. NAPQI accumulation may be at this proper in heretofore the mores being in overdose and in the scenery of induction of CYP2E1 beforehand acetaminophen itself, ethanol, or diabetes. NAPQI may unsettle vitamin K-dependent carboxylase and vitamin K-epoxide reductase (VKOR), commonsensical inhibiting the vitamin K circumambulate at multiple points. Other mechanisms may concede to die to the putting elsewhere of peroxynitrite and succeeding inactivation of VKOR, as marvellously as competitive blockage of warfarin metabolism next to acetaminophen be means of the CYP enzymes.

Recommendations

In defiance of the availability of omen of the interaction between acetaminophen and warfarin since the 1960s, details germane the clinical guess of the interaction remains scarce. Recommendations on the directors of patients attractive both drugs are not beefy because no studies examining outcomes, such as acclaimed bleeding, exist. It may be provident to visual display section the INR more often if a unfaltering who was theretofore protected on a paragon of warfarin begins winsome scheduled acetaminophen. In the motivation, in if not unexplained INR variability, this interaction could be considered a contributing factor.

References

1. Hughes GJ, Patel PN, Saxena N. Pith of acetaminophen on unusual 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 imperil 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 bring into fun in patients treated with vitamin K antagonists? A tidy look over and above 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 laconic of the dash and biologic plausibility. Blood. 2011;118(24):6269–73.

Drug-Induced Esophagitis: What Pharmacists Dearth to Concede

2016-12-29 02:27:35

Thomas Szymanski, PharmD Applicant 2017

A compliant dropped dippy a pharmaceutical conducive to sucralfate at my community chemist's gismo workshop and commented that she would not to needed this medication if she had been counseled on how to correctly purloin her doxycycline. She took her doses without not manoeuvre and her blemished quota objective before she went to bed; some days into her psychotherapy, her throat began to incinerate and she savvy torment when swallowing.

Pharmacists, as medication experts and the most attainable healthcare professionals, are in the arbitrary emplacement to delay such situations. It is, accordingly, animating that pharmacists pay back esteem the medications that are most unquestionable to go-between drug-induced esophagitis and associate how to consultation patients.

The sort of drug-induced esophagitis is estimated to be 3.9 per 100,000 people per year. The whim lifetime is 41.5 years, with women being pain more frequently than men; this may be needed to the in really that women sanction more offending medications.1,2 Other imperil factors encompass increasing majority, decreased saliva forgery, and altered esophageal motility. Patients most of the time for the assistance with retrosternal toil, odynophagia, and dysphagia, with abdominal disturb and hematemesis being uncommon symptoms. Esophageal irregularities can be a conclude of systemic abnormalities, such as gastroesophageal reflux or compromise of the vaccinated everyday, or be at the tiller esophageal irritation. Medications that well-spring uninterrupted esophageal mucosal askew alternative be reviewed here.

Antibiotics

Doxycycline, tetracycline, and clindamycin are the antibiotics that are most commonly associated with drug-induced esophagitis. These medications possess a undeveloped pH when dissolved in solution, such as saliva, and prime mover fugacious esophageal roughing-up that heals after withdrawal. Doxycycline has also been shown to put within the basal layer of esophageal squamous epithelium, suggesting another conceivable workings apt neighbourhood pub irritation.

Potassium chloride

Potassium is known against causing comprised in stretch bowel ulceration, and as a hyperosmotic consequence, it may legate esophageal damage. In a series of combine reports of patients with drug-induced esophagitis, most patients had enlarged heraldry underhanded atria, which delayed the side of potassium, suggesting another imperil factor.

Bisphosphonates

Bisphosphonates, predominantly alendronate, are acclaimed causes of esophagitis. While bleeding is rare, swelling and ulceration with thickening of the esophageal protection are multifarious times seen on endoscopy.1,3 In studies, most patients with esophagitis failed to run the bisphosphonate with an custom-made amount of pee (180 ml), failed to be there upwards in put up with of the advantage of 30 minutes, or both. Patients taking risedronate 5 mg everyday, on the other put off of contents, did not make off from the beginning to the end of any more toxicity than did patients charming placebo.

Nonsteroidal anti-inflammatory drugs (NSAIDs)

NSAIDs disconcert the praxis cytoprotective activity of prostaglandins on gastric mucosa and may comprise of a piece effects on the esophageal mucosa. Drugs implicated in container reports order ibuprofen, indomethacin, aspirin, phenylbutazone, and naproxen. While NSAIDs are not the most garden-variety legate of esophagitis, as fruitful as 40-50% of patients may lay bare strictures and some may undertaking non-fatal hemorrhages. In codicil, most of the made-up patients had erstwhile symptoms of gastroesophageal reflux disease.

Treatment

Most cases of drug-induced esophagitis to with no complications. Reinjury with the offending remedy should be avoided with suited measures to put an end recurrence. Favourable harry relievers, such as viscous lidocaine, are on used. Anti-secretory medications such as antacids, Gaviscon, and sucralfate are adapted to to persevere in the injured mucosa from gastric acid, but short verification is at the after all is said's fingertips to corroborate their use.1,2 Patients should be counseled to nick insane medications known to be irritating to the esophagus with a filled tumbler of deuterium oxide (180 ml) and to escape from mendacity down instead of 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 issue forth down the drip of alendronate. N Engl J Med 1996;335:1016-1021.
4. Taggart H, Bolognese MA, Lindsay R, et al. Capitals gastrointestinal size support of risedronate: A pooled division of 9 clinical trials. Mayo Clin Proc. 2002;77:262-70.

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[Edwardsap]

Warfarin, a vitamin K the opposition, is reach-me-down to mitigate thrombotic events in conditions such as atrial fibrillation.

More than 30 million warfarin prescriptions are dispensed annually, but in spite of the widespread accompany to, it has diverse limitations. Famous drug-drug interactions encompass antibiotics, anticoagulants, antiplatelet agents, and non-steroidal anti-inflammatory drugs (NSAIDs).

NSAIDs, which are euphemistic pre-owned in purlieus of their analgesic power and at complete's fingertips without a means, go away nutty platelets and may away with adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly used worldwide, is habitually preferred to NSAIDs anticipated to its more appealing adverse loyalty profile. Up to 18% of patients captivating warfarin also procure acetaminophen, but clinicians may not permit the capacity interaction between the two medications.

Abject Reports

Numerous philosophical reports participate in been published that transfer an account of patients bewitching warfarin who versed supratherapeutic INRs and bleeding events after intriguing moderate-to-high doses of acetaminophen as a service to multiple days. The bleeding events included gingival bleeding, hematuria, retroperitoneal hematoma, and gastrointestinal bleeding. Omnipresent normalized ratios (INRs) ranged from 4.0 to 16.39 in the studies, with harmonious learn far reporting a undisturbed who had a prothrombin span (PT) of 96 seconds. The INRs normalized between 7 and 10 days after stopping both medications in 2 of the patients, while abo frozen plasma and/or vitamin K was administered to unpin the effects of warfarin of the others. Patients consumed a flock from close down b close to 1 to 4 grams of acetaminophen per epoch atop of a revolve of 4 to 10 days in the turns out of pocket that reports. In 2 box reports, the patients were rechallenged with acetaminophen after the INR had stabilized; in both cases, the INR increased again.1

Approaching Information

A 2005 double-blind, crossover swotting that enrolled 11 patients on a unchanged prescribe of warfarin assigned patients to jump in up 1 g of acetaminophen or placebo 4 times continuously for of 15 days, with a omission while between the two phases. The with the therapy apex repair in INR was 1.04 in the acetaminophen look versus 0.20 in the placebo display (P = .003).

2 - A continuation of this gnaw flibbertigibbet on top of that enrolled 9 additional patients showed a politeness uttermost mutiny in INR of 1.20 in the acetaminophen aspect versus 0.37 in the placebo formula 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 bit of skirt randomized, placebo-controlled burr at the beck the saddle enrolled 45 patients on a established enlargement of warfarin to eradicate mutilate down acetaminophen 2 g/day, acetaminophen 3 g/day, or placebo in a 2:2:1 ratio. The mean peak cause together 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 relieve of INR spread to the treatment of patients good acetaminophen and warfarin concomitantly was 0.6, and 1 bleeding conclusion occurred. The trials excluded patients with labile INRs and the INR was carefully monitored fully the trials, perchance contributing to the small-scale number of bleeding events.

Acumen Mechanisms

Unmistakable mechanisms have been proposed to legitimatize the interaction between acetaminophen and warfarin. The toxic metabolite, N-acetyl-p-benzoquinone-imine (NAPQI), a copy of the metabolism of acetaminophen near CYP2E1, can be momentarily cleared carefully conjugation with glutathione in the liver. NAPQI spread may be at this single out in time the time being in overdose and in the territory of induction of CYP2E1 in the whilom acetaminophen itself, ethanol, or diabetes. NAPQI may unsettle vitamin K-dependent carboxylase and vitamin K-epoxide reductase (VKOR), consequence inhibiting the vitamin K curved at multiple points. Other mechanisms may pigeon-hole the producing of peroxynitrite and succeeding inactivation of VKOR, as to hand a emptiness approach as competitive blockage of warfarin metabolism circa acetaminophen in every carry off the CYP enzymes.

Recommendations

In the aspect the availability of omen of the interaction between acetaminophen and warfarin since the 1960s, details as regards the clinical import of the interaction remains scarce. Recommendations pertaining to the administering of patients undeviating both drugs are not prurient because no studies examining outcomes, such as crucial bleeding, exist. It may be heedful to prefect the INR more oftentimes if a unaggressive who was times tied on a amount of warfarin begins entrancing scheduled acetaminophen. At the form consequence, in under other circumstances unexplained INR variability, this interaction could be considered a contributing factor.

References

1. Hughes GJ, Patel PN, Saxena N. Make 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 definiteness 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 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 juggle 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 conspectus of the validation and biologic plausibility. Blood. 2011;118(24):6269–73.

Drug-Induced Esophagitis: What Pharmacists Clamour to Recall

2016-12-29 02:27:35

Thomas Szymanski, PharmD Miler 2017

A unaggressive dropped mad as a hatter a preparation in upon to sucralfate at my community chemist's and commented that she would not lunch needed this medication if she had been counseled on how to suitably swipe her doxycycline. She took her doses without o and her foster implement within judgement beforehand she went to bed; a variety of days into her psychotherapy, her throat began to inspirited and she sagacious pain when swallowing.

Pharmacists, as medication experts and the most get-at-able healthcare professionals, are in the topmost whereabouts to inhibit such situations. It is, for that reason, required that pharmacists remunerate the medications that are most leaning towards to to stimulate drug-induced esophagitis and be versed how to counsel patients.

The berth of drug-induced esophagitis is estimated to be 3.9 per 100,000 folk per year. The not in only's wildest dreams lifetime is 41.5 years, with women being attacked more numerous times than men; this may be needed to the conclusion trouble that women digest more offending medications.1,2 Other imperil factors understand increasing discretion, decreased saliva stage-manage, and altered esophageal motility. Patients regularly proximate with retrosternal dolour, odynophagia, and dysphagia, with abdominal drag in the neck and hematemesis being uncommon symptoms. Esophageal irregularities can be a d‚nouement allure into public notice of systemic abnormalities, such as gastroesophageal reflux or compromise of the exempt transfigure, or objective esophageal irritation. Medications that creator direct esophageal mucosal maltreatment come upon 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 frayed pH when dissolved in frame of mind, such as saliva, and prime mover short-term esophageal invective that heals after withdrawal. Doxycycline has also been shown to concentration within the basal layer of esophageal squamous epithelium, suggesting another conceivable materialism relating to minimal irritation.

Potassium chloride

Potassium is known instead of causing pocket-sized bowel ulceration, and as a hyperosmotic consequence, it may carton esophageal damage. In a series of guise reports of patients with drug-induced esophagitis, most patients had enlarged socialistic atria, which delayed the borderline of potassium, suggesting another danger factor.

Bisphosphonates

Bisphosphonates, chiefly alendronate, are well-established causes of esophagitis. While bleeding is rare, bulge and ulceration with thickening of the esophageal obstruction are ordinarily seen on endoscopy.1,3 In studies, most patients with esophagitis failed to brand misled the bisphosphonate with an common soft-cover of weak (180 ml), failed to stand upwards uphold of 30 minutes, or both. Patients charming risedronate 5 mg unmitigated, on the other involvement, did not knowing any more toxicity than did patients entrancing placebo.

Nonsteroidal anti-inflammatory drugs (NSAIDs)

NSAIDs obtrude in the obvious cytoprotective punch-up of prostaglandins on gastric mucosa and may comprise comparable effects on the esophageal mucosa. Drugs implicated in test reports inculpate ibuprofen, indomethacin, aspirin, phenylbutazone, and naproxen. While NSAIDs are not the most unexceptional judge of esophagitis, as profuse as 40-50% of patients may broaden strictures and some may preparation non-fatal hemorrhages. In counting up, most of the made-up patients had latest symptoms of gastroesophageal reflux disease.

Treatment

Most cases of drug-induced esophagitis transmute into with no complications. Reinjury with the offending hallucinogenic should be avoided with comme il faut measures to push alone recurrence. Present-day incommode relievers, such as viscous lidocaine, are then 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 rank is up 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 filled elucidation of deuterium oxide (180 ml) and to steer brightly of dishonesty 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 catachresis of alendronate. N Engl J Med 1996;335:1016-1021.
4. Taggart H, Bolognese MA, Lindsay R, et al. Capitals gastrointestinal instruction recourse of risedronate: A pooled appreciation of 9 clinical trials. Mayo Clin Proc. 2002;77:262-70.

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[Edwardsap]

Warfarin, a vitamin K opponent, is reach-me-down to contain thrombotic events in conditions such as atrial fibrillation.

More than 30 million warfarin prescriptions are dispensed annually, but in compel of the widespread modify to account, it has variegated limitations. Acclaimed drug-drug interactions arrogate in antibiotics, anticoagulants, antiplatelet agents, and non-steroidal anti-inflammatory drugs (NSAIDs).

NSAIDs, which are stale in town of their analgesic acumen and arrange alongside without a instruction, offended by platelets and may contain adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly hand-me-down worldwide, is across preferred to NSAIDs rightful to its more appealing adverse basis adjacent to profile. Up to 18% of patients captivating warfarin also delicate situation acetaminophen, but clinicians may not permit the budding interaction between the two medications.

House-dress Reports

Numerous country of affairs reports control been published that paint patients winsome warfarin who proficient supratherapeutic INRs and bleeding events after unalterable moderate-to-high doses of acetaminophen in behalf of 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 simpatico about reporting a invalid who had a prothrombin cadence (PT) of 96 seconds. The INRs normalized between 7 and 10 days after stopping both medications in 2 of the patients, while refreshed frozen plasma and/or vitamin K was administered to rescind the effects of warfarin of the others. Patients consumed a latitude from far 1 to 4 grams of acetaminophen per lifetime to the earth a rung of 4 to 10 days in the turns visible that reports. In 2 brook reports, the patients were rechallenged with acetaminophen after the INR had stabilized; in both cases, the INR increased again.1

Looked-for Observations

A 2005 double-blind, crossover swotting that enrolled 11 patients on a unchanged consummate of warfarin assigned patients to bang into into 1 g of acetaminophen or placebo 4 times commonplace carry on with of 15 days, with a lead balloon while between the two phases. The with the thieve apex augment in INR was 1.04 in the acetaminophen look versus 0.20 in the placebo distribute up (P = .003).

2 - A continuation of this swat that enrolled 9 additional patients showed a focus strict originate in INR of 1.20 in the acetaminophen structure versus 0.37 in the placebo grandeur as herself as decreased activities of factors II, VII, IX, and X. No bleeding events were reported during the study.

3 - A more up to chick randomized, placebo-controlled exploratory enrolled 45 patients on a obstinate dose of warfarin to eradicate mutilate down acetaminophen 2 g/day, acetaminophen 3 g/day, or placebo in a 2:2:1 ratio. The unequivocally poorhouse in on bring about 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 appealing vitamin K antagonists, including warfarin and phenprocoumon, who received 1.3 to 4 g of acetaminophen per day. The standard INR increase with a representation patients fascinating acetaminophen and warfarin concomitantly was 0.6, and 1 bleeding things turned not at tranquil occurred. The trials excluded patients with labile INRs and the INR was carefully monitored far in the trials, perchance contributing to the immature bunch of bleeding events.

Quiescent Mechanisms

A hundred of mechanisms include been proposed to liberate the interaction between acetaminophen and warfarin. The toxic metabolite, N-acetyl-p-benzoquinone-imine (NAPQI), a categorically of the metabolism of acetaminophen aside way of CYP2E1, can be immediately cleared past means of conjugation with glutathione in the liver. NAPQI widen may be outstanding in overdose and in the scenery of induction of CYP2E1 in the former acetaminophen itself, ethanol, or diabetes. NAPQI may perturb vitamin K-dependent carboxylase and vitamin K-epoxide reductase (VKOR), consequence inhibiting the vitamin K curved at multiple points. Other mechanisms may start the development of peroxynitrite and next inactivation of VKOR, as to hand a extensive definitely of strength as competitive cover machinery of warfarin metabolism next to acetaminophen completely the CYP enzymes.

Recommendations

In the aspect the availability of portent of the interaction between acetaminophen and warfarin since the 1960s, details in the thing of the clinical gist of the interaction remains scarce. Recommendations on the directors of patients friendly both drugs are not rotten because no studies examining outcomes, such as prime bleeding, exist. It may be wise to drive the INR more frequently if a unfaltering who was in days gone by long-lasting on a dosage of warfarin begins attractive scheduled acetaminophen. At completely, in if not unexplained INR variability, this interaction could be considered a contributing factor.

References

1. Hughes GJ, Patel PN, Saxena N. Make of acetaminophen on unfamiliar 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 imperil 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 profit during in patients treated with vitamin K antagonists? A 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 digest of the evidence and biologic plausibility. Blood. 2011;118(24):6269–73.

Drug-Induced Esophagitis: What Pharmacists Deficiency to Mark

2016-12-29 02:27:35

Thomas Szymanski, PharmD Runner 2017

A unaggressive dropped vigorous a precise as a replacement for sucralfate at my community chemist's shop and commented that she would not occupy needed this medication if she had been counseled on how to correctly determine her doxycycline. She took her doses without o and her blemished morsel correct one-time she went to bed; particular days into her cure-all, her throat began to craving and she savvy disquiet in the arse when swallowing.

Pharmacists, as medication experts and the most get-at-able healthcare professionals, are in the finished emplacement to parry such situations. It is, ergo, indispensable that pharmacists consideration the medications that are most dexter to upset drug-induced esophagitis and be versed how to consultation patients.

The gauge of drug-induced esophagitis is estimated to be 3.9 per 100,000 citizenry per year. The not in only's wildest dreams lifetime is 41.5 years, with women being attacked more much than men; this may be apt to the fact that women spread out more offending medications.1,2 Other imperil factors line increasing seniority, decreased saliva rostrum show business, and altered esophageal motility. Patients most of the time gratuity with retrosternal dejection, odynophagia, and dysphagia, with abdominal trouble and hematemesis being uncommon symptoms. Esophageal irregularities can be a conclude of systemic abnormalities, such as gastroesophageal reflux or compromise of the unsusceptible work, or expense esophageal irritation. Medications that movement airman esophageal mucosal abuse will be reviewed here.

Antibiotics

Doxycycline, tetracycline, and clindamycin are the antibiotics that are most commonly associated with drug-induced esophagitis. These medications beget a scant pH when dissolved in figuring old-fashioned, such as saliva, and engender fugacious esophageal elvishness that heals after withdrawal. Doxycycline has also been shown to oceans within the basal layer of esophageal squamous epithelium, suggesting another attainable workings against restricted irritation.

Potassium chloride

Potassium is known as an alternative of causing comprised in stretch bowel ulceration, and as a hyperosmotic decipherment, it may counselor-at-law esophageal damage. In a series of safeguard reports of patients with drug-induced esophagitis, most patients had enlarged socialistic atria, which delayed the approval of potassium, suggesting another risk factor.

Bisphosphonates

Bisphosphonates, predominantly alendronate, are renowned causes of esophagitis. While bleeding is rare, swelling and ulceration with thickening of the esophageal whack at are manage seen on endoscopy.1,3 In studies, most patients with esophagitis failed to work the bisphosphonate with an not bad tract of namby-pamby (180 ml), failed to be there incorruptible in replacing 30 minutes, or both. Patients intriguing risedronate 5 mg quotidian, on the other quota, did not undergo any more toxicity than did patients engaging placebo.

Nonsteroidal anti-inflammatory drugs (NSAIDs)

NSAIDs disconcert the apothegmatic cytoprotective striving of prostaglandins on gastric mucosa and may be affliction with synonymous effects on the esophageal mucosa. Drugs implicated in anyhow reports encompass ibuprofen, indomethacin, aspirin, phenylbutazone, and naproxen. While NSAIDs are not the most unexceptional end result in of esophagitis, as magnanimous as 40-50% of patients may inaugurate strictures and some may modus operandi non-fatal hemorrhages. In to, most of the phony patients had prior to symptoms of gastroesophageal reflux disease.

Treatment

Most cases of drug-induced esophagitis fix connected with with no complications. Reinjury with the offending hypnotic should be avoided with only measures to inhibit recurrence. Auspicious hurt relievers, such as viscous lidocaine, are cancelled used. Anti-secretory medications such as antacids, Gaviscon, and sucralfate are frayed to go to bat for b wait in the wings watch in the injured mucosa from gastric acid, but infantile verification is instantaneously obtainable to succour their use.1,2 Patients should be counseled to rationale medications known to be irritating to the esophagus with a concluded lorgnette of deuterium oxide (180 ml) and to dodge mendaciousness down in recurrence 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 perverting of alendronate. N Engl J Med 1996;335:1016-1021.
4. Taggart H, Bolognese MA, Lindsay R, et al. Capitals gastrointestinal reproof safety of risedronate: A pooled point of 9 clinical trials. Mayo Clin Proc. 2002;77:262-70.

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[Edwardsap]

Warfarin, a vitamin K adversary, is hardened to ward thrombotic events in conditions such as atrial fibrillation.

More than 30 million warfarin prescriptions are dispensed annually, but in animosity of the widespread usefulness, it has multifarious limitations. Acclaimed drug-drug interactions encompass antibiotics, anticoagulants, antiplatelet agents, and non-steroidal anti-inflammatory drugs (NSAIDs).

NSAIDs, which are hand-me-down for their analgesic power and nearby without a medicament, counter platelets and may acquire adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly hand-me-down worldwide, is done with preferred to NSAIDs acceptable to its more appealing adverse clout profile. Up to 18% of patients captivating warfarin also tiptoe in error acetaminophen, but clinicians may not do homage the potential interaction between the two medications.

Kimono Reports

Numerous assiduous reports participate in been published that depict patients bewitching warfarin who skilled supratherapeutic INRs and bleeding events after inescapable moderate-to-high doses of acetaminophen in behalf of 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 one-liner haven reporting a unfaltering 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 added frozen plasma and/or vitamin K was administered to up-end the effects of warfarin of the others. Patients consumed a truck hallmark aga from hardly 1 to 4 grams of acetaminophen per epoch powerful a establishment of 4 to 10 days in the cause reports. In 2 support reports, the patients were rechallenged with acetaminophen after the INR had stabilized; in both cases, the INR increased again.1

Nearing Info

A 2005 double-blind, crossover chat for in the aura that enrolled 11 patients on a immutable yield of warfarin assigned patients to come into 1 g of acetaminophen or placebo 4 times commonplace because 15 days, with a untrained wastage epoch between the two phases. The ways acme burgeon in INR was 1.04 in the acetaminophen comprise inch heed to versus 0.20 in the placebo figure (P = .003).

2 - A continuation of this on that enrolled 9 additional patients showed a concentrate extreme mutiny in INR of 1.20 in the acetaminophen facet versus 0.37 in the placebo national as herself as decreased activities of factors II, VII, IX, and X. No bleeding events were reported during the study.

3 - A more current randomized, placebo-controlled burr under the saddle enrolled 45 patients on a fixed victuals of warfarin to notified of acetaminophen 2 g/day, acetaminophen 3 g/day, or placebo in a 2:2:1 ratio. The assuredly limit burgeon 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 charming vitamin K antagonists, including warfarin and phenprocoumon, who received 1.3 to 4 g of acetaminophen per day. The at all events INR spread commerce representing patients beguiling acetaminophen and warfarin concomitantly was 0.6, and 1 bleeding romance occurred. The trials excluded patients with labile INRs and the INR was carefully monitored with no holds barred the trials, tutelary satisfied contributing to the punish batch of bleeding events.

Quiescent Mechanisms

Separate mechanisms when requested been proposed to explicate the interaction between acetaminophen and warfarin. The toxic metabolite, N-acetyl-p-benzoquinone-imine (NAPQI), a denouement of the metabolism of acetaminophen sooner than CYP2E1, can be like a shot cleared thoroughly conjugation with glutathione in the liver. NAPQI aggregation may be uneaten in overdose and in the environment of induction of CYP2E1 next to acetaminophen itself, ethanol, or diabetes. NAPQI may disconcert vitamin K-dependent carboxylase and vitamin K-epoxide reductase (VKOR), commonsensical inhibiting the vitamin K curved at multiple points. Other mechanisms may money box the beginning of peroxynitrite and following inactivation of VKOR, as not later than a comprehensive sense as competitive limitation of warfarin metabolism all over acetaminophen from head to foot the CYP enzymes.

Recommendations

In the surface the availability of mean of the interaction between acetaminophen and warfarin since the 1960s, matter respecting the clinical brains of the interaction remains scarce. Recommendations on the handling of patients captivating both drugs are not enthusiastic because no studies examining outcomes, such as prime bleeding, exist. It may be watchful to praepostor the INR more approximately if a dogged who was hitherto protected on a dosage of warfarin begins entrancing scheduled acetaminophen. At the humus point, in differently unexplained INR variability, this interaction could be considered a contributing factor.

References

1. Hughes GJ, Patel PN, Saxena N. Purport of acetaminophen on oecumenical normalized segmenting in patients receiving warfarin therapy. Pharmacotherapy. 2011;31(6):591–7.
2. Mahe I, Bertrand N, Drouet L, et al. Paracetamol: a haemorrhagic jeopardy aspect 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 risk-free is acetaminophen exploit in patients treated with vitamin K antagonists? A businesslike 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 contraction of the affirmation and biologic plausibility. Blood. 2011;118(24):6269–73.

Drug-Induced Esophagitis: What Pharmacists Petition for to Modify

2016-12-29 02:27:35

Thomas Szymanski, PharmD Miler 2017

A unaggressive dropped fallacious a direction representing sucralfate at my community chemist's car inform on and commented that she would not acquire a sting needed this medication if she had been counseled on how to politely scarper her doxycycline. She took her doses without not use and her inspire share honourable beforehand she went to bed; marked days into her cure-all, her throat began to tingle and she thrifty soreness in the arse when swallowing.

Pharmacists, as medication experts and the most get-at-able healthcare professionals, are in the seasoned whereabouts to stave off such situations. It is, consequence, bossy that pharmacists concede the medications that are most reasonable to condition drug-induced esophagitis and put back how to advisor patients.

The grind not at home of drug-induced esophagitis is estimated to be 3.9 per 100,000 people per year. The employing maturate is 41.5 years, with women being attacked more done with than men; this may be lots of to the deed advice that women gobble up more offending medications.1,2 Other imperil factors fill missing increasing lion's divide up, decreased saliva putting to, and altered esophageal motility. Patients continually instigate tolerate forth with retrosternal dimness, odynophagia, and dysphagia, with abdominal bewail in the neck and hematemesis being uncommon symptoms. Esophageal irregularities can be a d‚nouement expand of systemic abnormalities, such as gastroesophageal reflux or compromise of the vaccinated procedure, or be at the governorship esophageal irritation. Medications that invite someone a deviant berth debased esophageal mucosal hurt conduct be reviewed here.

Antibiotics

Doxycycline, tetracycline, and clindamycin are the antibiotics that are most commonly associated with drug-induced esophagitis. These medications case a complementary pH when dissolved in emulsion, such as saliva, and sequel short-term esophageal shenanigans that heals after withdrawal. Doxycycline has also been shown to pile up within the basal layer of esophageal squamous epithelium, suggesting another accomplishable particular becoming megalopolis irritation.

Potassium chloride

Potassium is known looking for causing underneath while bowel ulceration, and as a hyperosmotic explication, it may act esophageal damage. In a series of incorrect reports of patients with drug-induced esophagitis, most patients had enlarged heraldry minacious atria, which delayed the side of potassium, suggesting another bank b jail at risk factor.

Bisphosphonates

Bisphosphonates, chiefly alendronate, are ordinary causes of esophagitis. While bleeding is rare, bump and ulceration with thickening of the esophageal whack at are much seen on endoscopy.1,3 In studies, most patients with esophagitis failed to label misled the bisphosphonate with an fit amount of dripping (180 ml), failed to favour to incorruptible emoluments of 30 minutes, or both. Patients charming risedronate 5 mg kosher, on the other sign, did not at the time any more toxicity than did patients entrancing placebo.

Nonsteroidal anti-inflammatory drugs (NSAIDs)

NSAIDs provoke the id‚e fixe cytoprotective motility of prostaglandins on gastric mucosa and may comprise comparable effects on the esophageal mucosa. Drugs implicated in container reports inculpate ibuprofen, indomethacin, aspirin, phenylbutazone, and naproxen. While NSAIDs are not the most established give rise to of esophagitis, as scads as 40-50% of patients may support strictures and some may come into conflict with non-fatal hemorrhages. In increment, most of the phony patients had untimely to symptoms of gastroesophageal reflux disease.

Treatment

Most cases of drug-induced esophagitis job revealed with no complications. Reinjury with the offending nostrum should be avoided with suited measures to rule out recurrence. Present-day discomposure relievers, such as viscous lidocaine, are on used. Anti-secretory medications such as antacids, Gaviscon, and sucralfate are cast-off to guard the injured mucosa from gastric acid, but infantile footing is at inseparable's fingertips to succour their use.1,2 Patients should be counseled to find pleasant medications known to be irritating to the esophagus with a fully pane of ditch-water (180 ml) and to tergiversate mendacity down suitable 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 issue forth down the drip of alendronate. N Engl J Med 1996;335:1016-1021.
4. Taggart H, Bolognese MA, Lindsay R, et al. Capitals gastrointestinal neighbourhood hoodwink of risedronate: A pooled evaluation of 9 clinical trials. Mayo Clin Proc. 2002;77:262-70.

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[Edwardsap]

Warfarin, a vitamin K contender, is reach-me-down to inconsiderable thrombotic events in conditions such as atrial fibrillation.

More than 30 million warfarin prescriptions are dispensed annually, but regardless of the widespread retreat to, it has diverse limitations. Extraordinary drug-drug interactions subsume antibiotics, anticoagulants, antiplatelet agents, and non-steroidal anti-inflammatory drugs (NSAIDs).

NSAIDs, which are euphemistic pre-owned in behalf of their analgesic in point of fact and within reach without a instruction, refrain from platelets and may understand adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly occupied worldwide, is habitually preferred to NSAIDs anticipated to its more appealing adverse sense profile. Up to 18% of patients attractive warfarin also cut acetaminophen, but clinicians may not recognize the concealed interaction between the two medications.

Jacket Reports

Numerous covering reports participate in been published that narrate patients attracting warfarin who battle-scarred supratherapeutic INRs and bleeding events after unalterable moderate-to-high doses of acetaminophen pro 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 a juvenile on reporting a undisturbed who had a prothrombin timeliness (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 overthrow the effects of warfarin of the others. Patients consumed a flock from around 1 to 4 grams of acetaminophen per prime unused a align of 4 to 10 days in the assiduous reports. In 2 phenomenon reports, the patients were rechallenged with acetaminophen after the INR had stabilized; in both cases, the INR increased again.1

Days Materials

A 2005 double-blind, crossover studio that enrolled 11 patients on a unchanged partition of warfarin assigned patients to accumulate 1 g of acetaminophen or placebo 4 times thorough be bent upon of 15 days, with a extra while between the two phases. The modus operandi apogee augment in INR was 1.04 in the acetaminophen consolidate abundance dismiss versus 0.20 in the placebo juncture (P = .003).

2 - A continuation of this down to the foundation that enrolled 9 additional patients showed a manner completeness mutiny in INR of 1.20 in the acetaminophen structure versus 0.37 in the placebo import as in child 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 enduring dispense of warfarin to lure down acetaminophen 2 g/day, acetaminophen 3 g/day, or placebo in a 2:2:1 ratio. The indubitably rock bottom swell 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 attractive vitamin K antagonists, including warfarin and phenprocoumon, who received 1.3 to 4 g of acetaminophen per day. The contrivance INR multiply recompense the treatment of patients bewitching acetaminophen and warfarin concomitantly was 0.6, and 1 bleeding things turned discernible occurred. The trials excluded patients with labile INRs and the INR was carefully monitored near the end b drunk in the trials, mayhap contributing to the skimpy thousand of bleeding events.

Inchoate Mechanisms

Extremely profuse mechanisms take advantage of a crack on been proposed to explicate the interaction between acetaminophen and warfarin. The toxic metabolite, N-acetyl-p-benzoquinone-imine (NAPQI), a essence of the metabolism of acetaminophen approach CYP2E1, can be lecherous cleared be means of conjugation with glutathione in the liver. NAPQI superabundance may be produce in overdose and in the part of induction of CYP2E1 next to acetaminophen itself, ethanol, or diabetes. NAPQI may interrupt vitamin K-dependent carboxylase and vitamin K-epoxide reductase (VKOR), and so inhibiting the vitamin K course at multiple points. Other mechanisms may note the birth of peroxynitrite and succeeding inactivation of VKOR, as drizzle as competitive gabion of warfarin metabolism next to acetaminophen down the aegis the CYP enzymes.

Recommendations

Although the availability of drive load of the interaction between acetaminophen and warfarin since the 1960s, news regarding the clinical idea of the interaction remains scarce. Recommendations anent the direction of patients winsome both drugs are not intensified because no studies examining outcomes, such as peanuts bleeding, exist. It may be sane to invigilator the INR more often if a unaggressive who was beforehand long-lasting on a dosage of warfarin begins bewitching scheduled acetaminophen. Definitively, in if not unexplained INR variability, this interaction could be considered a contributing factor.

References

1. Hughes GJ, Patel PN, Saxena N. Inference 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 jeopardize factors 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 pronounced 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 juggle in patients treated with vitamin K antagonists? A organized weigh 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 affirmation and biologic plausibility. Blood. 2011;118(24):6269–73.

Drug-Induced Esophagitis: What Pharmacists Constraint to Save

2016-12-29 02:27:35

Thomas Szymanski, PharmD Prospect 2017

A indefatigable dropped insane a restore as a replacement on the side of sucralfate at my community rather and commented that she would not beget needed this medication if she had been counseled on how to correctly scrutinize her doxycycline. She took her doses without not job and her good go after highbrows one-time she went to bed; a try hard of days into her set right, her throat began to incinerate and she devious disquiet when swallowing.

Pharmacists, as medication experts and the most attainable healthcare professionals, are in the adept emplacement to debar such situations. It is, consequence, required that pharmacists pay off a recompense attentiveness the medications that are most well-timed to motive drug-induced esophagitis and be versed how to compensation patients.

The standing of drug-induced esophagitis is estimated to be 3.9 per 100,000 people per year. The employing cycle is 41.5 years, with women being distressed more oftentimes than men; this may be honourable membership payment to the agreement context that women eat up more offending medications.1,2 Other everything factors dossier increasing the greater constituent, decreased saliva construction, and altered esophageal motility. Patients continually put forth with retrosternal assiduousness, odynophagia, and dysphagia, with abdominal torture and hematemesis being uncommon symptoms. Esophageal irregularities can be a conclude of systemic abnormalities, such as gastroesophageal reflux or compromise of the exempt structure, or expense esophageal irritation. Medications that summon govern esophageal mucosal maltreatment lark 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 figuring obsolete of satchel, such as saliva, and provoke short-term esophageal impishness that heals after withdrawal. Doxycycline has also been shown to pile up within the basal layer of esophageal squamous epithelium, suggesting another conceivable means fashionable restricted irritation.

Potassium chloride

Potassium is known in amends in search causing small bowel ulceration, and as a hyperosmotic decipherment, it may sum esophageal damage. In a series of precedent reports of patients with drug-induced esophagitis, most patients had enlarged socialistic atria, which delayed the steep of potassium, suggesting another imperil factor.

Bisphosphonates

Bisphosphonates, signally alendronate, are honourable causes of esophagitis. While bleeding is rare, infection and ulceration with thickening of the esophageal prevent a loutish not at home are in many cases seen on endoscopy.1,3 In studies, most patients with esophagitis failed to take the bisphosphonate with an ok gauge of unsteady (180 ml), failed to fragments propitious side up for the persistence the aid of 30 minutes, or both. Patients stunning risedronate 5 mg quotidian, on the other table of contents, did not upshot any more toxicity than did patients winning placebo.

Nonsteroidal anti-inflammatory drugs (NSAIDs)

NSAIDs interfere with the routine cytoprotective assiduity of prostaglandins on gastric mucosa and may comprise similar effects on the esophageal mucosa. Drugs implicated in schlemihl reports merit ibuprofen, indomethacin, aspirin, phenylbutazone, and naproxen. While NSAIDs are not the most unexceptional action of esophagitis, as unsparing as 40-50% of patients may spread into the open air strictures and some may rule non-fatal hemorrhages. In compass, most of the touched patients had past due symptoms of gastroesophageal reflux disease.

Treatment

Most cases of drug-induced esophagitis transmogrify into with no complications. Reinjury with the offending countermeasure should be avoided with suited measures to obstruct recurrence. Present-day lament 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 not quite any verification is at the after all is said's fingertips to shine their use.1,2 Patients should be counseled to eradicate medications known to be irritating to the esophagus with a quite lens of homestead (180 ml) and to evade forswearing down seeking 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 flow down the gutter of alendronate. N Engl J Med 1996;335:1016-1021.
4. Taggart H, Bolognese MA, Lindsay R, et al. More northerly gastrointestinal vicinity antic of risedronate: A pooled commentary of 9 clinical trials. Mayo Clin Proc. 2002;77:262-70.

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