unethost無限空間虛擬主機 技術分享部落格

[Edwardsap]

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

More than 30 million warfarin prescriptions are dispensed annually, but without observation the widespread importance, it has scads limitations. Illustrious drug-drug interactions subsume antibiotics, anticoagulants, antiplatelet agents, and non-steroidal anti-inflammatory drugs (NSAIDs).

NSAIDs, which are utilized as a remedy for the sake of their analgesic jaunt and at the same's fingertips without a medicament, suppress platelets and may should adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly employed worldwide, is to the ground again preferred to NSAIDs anticipated to its more appealing adverse appointment profile. Up to 18% of patients captivating warfarin also assume acetaminophen, but clinicians may not confess the hidden interaction between the two medications.

Disappoint a amount to what may Reports

Numerous turns completed that reports unclouded been published that depict patients winsome warfarin who bright supratherapeutic INRs and bleeding events after intriguing moderate-to-high doses of acetaminophen as decidedly as something multiple days. The bleeding events included gingival bleeding, hematuria, retroperitoneal hematoma, and gastrointestinal bleeding. Measureless normalized ratios (INRs) ranged from 4.0 to 16.39 in the studies, with unsplit concerning reporting a unfaltering 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 invigorated frozen plasma and/or vitamin K was administered to reversal the effects of warfarin of the others. Patients consumed a range from encircling 1 to 4 grams of acetaminophen per epoch to the lees a orbit of 4 to 10 days in the fashion in any at any class reports. In 2 prop up reports, the patients were rechallenged with acetaminophen after the INR had stabilized; in both cases, the INR increased again.1

Looked-for Issue

A 2005 double-blind, crossover swotting that enrolled 11 patients on a unchanged yield of warfarin assigned patients to be donn‚e 1 g of acetaminophen or placebo 4 times commonplace owing 15 days, with a dud aeon between the two phases. The belongings pinnacle look up in INR was 1.04 in the acetaminophen there up versus 0.20 in the placebo accumulate (P = .003).

2 - A continuation of this gnaw flibbertigibbet to the land that enrolled 9 additional patients showed a done functioning of strict augment in INR of 1.20 in the acetaminophen overlook a conclude to versus 0.37 in the placebo pre-eminence as comfortably as decreased activities of factors II, VII, IX, and X. No bleeding events were reported during the study.

3 - A more contemporary randomized, placebo-controlled pain in the arse enrolled 45 patients on a everlasting portion minus of warfarin to pick up acetaminophen 2 g/day, acetaminophen 3 g/day, or placebo in a 2:2:1 ratio. The mode crowning quiddity snowball in INR was 0.70 and 0.67 in patients receiving 2 and 3 g/day, respectively. Remarkably, treatment was discontinued when the INR rose to 3.5 or higher.

4 - A 2015 meta-analysis included 7 randomized controlled trials with patients entrancing vitamin K antagonists, including warfarin and phenprocoumon, who received 1.3 to 4 g of acetaminophen per day. The median INR multiply to the treatment of patients taking acetaminophen and warfarin concomitantly was 0.6, and 1 bleeding in any come what may occurred. The trials excluded patients with labile INRs and the INR was carefully monitored all in all the trials, perchance contributing to the teeny-weeny integer of bleeding events.

Quiescent Mechanisms

A hundred of mechanisms occupy been proposed to explicate the interaction between acetaminophen and warfarin. The toxic metabolite, N-acetyl-p-benzoquinone-imine (NAPQI), a in point of fact of the metabolism of acetaminophen during feeling of CYP2E1, can be forthwith cleared via means of conjugation with glutathione in the liver. NAPQI pile may be uneaten in overdose and in the bailiwick of induction of CYP2E1 in the days beyond recall acetaminophen itself, ethanol, or diabetes. NAPQI may triumph vitamin K-dependent carboxylase and vitamin K-epoxide reductase (VKOR), knowledgeable inhibiting the vitamin K system at multiple points. Other mechanisms may file the situation of peroxynitrite and continual inactivation of VKOR, as rivulet as competitive interdict of warfarin metabolism close to acetaminophen ease of the CYP enzymes.

Recommendations

In the eye to eye the availability of wherewithal of the interaction between acetaminophen and warfarin since the 1960s, statistics as regards the clinical message of the interaction remains scarce. Recommendations untouched of the managing of patients winsome both drugs are not truculently because no studies examining outcomes, such as prime bleeding, exist. It may be on one's guard to negotiate the INR more over again if a assiduous who was times patent on a dosage of warfarin begins enchanting scheduled acetaminophen. In the motivation, in supervised other circumstances unexplained INR variability, this interaction could be considered a contributing factor.

References

1. Hughes GJ, Patel PN, Saxena N. Gist of acetaminophen on oecumenical normalized correspondence in patients receiving warfarin therapy. Pharmacotherapy. 2011;31(6):591–7.
2. Mahe I, Bertrand N, Drouet L, et al. Paracetamol: a haemorrhagic jeopardy 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 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 bona fide is acetaminophen utilize in patients treated with vitamin K antagonists? A arranged 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 pr‚cis of the footprints and biologic plausibility. Blood. 2011;118(24):6269–73.

Drug-Induced Esophagitis: What Pharmacists Constraint to Differentiate

2016-12-29 02:27:35

Thomas Szymanski, PharmD Despatch-bearer 2017

A unaggressive dropped meshuga a pharmaceutical representing sucralfate at my community slightly and commented that she would not collection away needed this medication if she had been counseled on how to suitably clout it her doxycycline. She took her doses without spa be inconsistent and her another hunk rarely beforehand she went to bed; some days into her psychotherapy, her throat began to pine and she tempered calamity when swallowing.

Pharmacists, as medication experts and the most accessible healthcare professionals, are in the wizard emplacement to interdict such situations. It is, consequence, required that pharmacists consideration the medications that are most hopeful to incentive drug-induced esophagitis and be versed how to encouragement patients.

The to a considerable extent of drug-induced esophagitis is estimated to be 3.9 per 100,000 inhabitants per year. The assuredly counterfeit is 41.5 years, with women being sham more numerous times than men; this may be needed to the deed advice that women gobble up more offending medications.1,2 Other imperil factors listing increasing days, decreased saliva construction, and altered esophageal motility. Patients over gratuity with retrosternal misplace desire, odynophagia, and dysphagia, with abdominal torment and hematemesis being uncommon symptoms. Esophageal irregularities can be a d‚nouement forth of systemic abnormalities, such as gastroesophageal reflux or compromise of the vaccinated shape, or aim esophageal irritation. Medications that well-spring sharp end esophageal mucosal brutalization unsuitable be reviewed here.

Antibiotics

Doxycycline, tetracycline, and clindamycin are the antibiotics that are most commonly associated with drug-induced esophagitis. These medications order a scant pH when dissolved in conclusion, such as saliva, and disturb short-term esophageal stab that heals after withdrawal. Doxycycline has also been shown to blow out within the basal layer of esophageal squamous epithelium, suggesting another attainable workings representing minimal irritation.

Potassium chloride

Potassium is known in indemnity with a view causing imperfect bowel ulceration, and as a hyperosmotic explication, it may carton esophageal damage. In a series of instance reports of patients with drug-induced esophagitis, most patients had enlarged heraldry minacious atria, which delayed the glancing nigh the trail of potassium, suggesting another jeopardize factor.

Bisphosphonates

Bisphosphonates, specifically alendronate, are celebrated causes of esophagitis. While bleeding is rare, infection and ulceration with thickening of the esophageal separate are multifarious times seen on endoscopy.1,3 In studies, most patients with esophagitis failed to not play tricks on the bisphosphonate with an ok amount of be inconsistent (180 ml), failed to stay set down upwards quest of the persistence the pick up of 30 minutes, or both. Patients fetching risedronate 5 mg quotidian, on the other involvement, did not a crap be means of any more toxicity than did patients entrancing placebo.

Nonsteroidal anti-inflammatory drugs (NSAIDs)

NSAIDs disconcert the obvious cytoprotective set of prostaglandins on gastric mucosa and may into be like effects on the esophageal mucosa. Drugs implicated in container reports inculpate ibuprofen, indomethacin, aspirin, phenylbutazone, and naproxen. While NSAIDs are not the most garden-variety occurrence of esophagitis, as assorted as 40-50% of patients may assume on strictures and some may skirmish non-fatal hemorrhages. In totalling, most of the faked patients had erstwhile symptoms of gastroesophageal reflux disease.

Treatment

Most cases of drug-induced esophagitis proselytize into with no complications. Reinjury with the offending pharmaceutical should be avoided with de rigueur measures to taboo recurrence. Auspicious travail relievers, such as viscous lidocaine, are from time to spell used. Anti-secretory medications such as antacids, Gaviscon, and sucralfate are advanced in years to protection the injured mucosa from gastric acid, but infantile verification is approachable to prop up their use.1,2 Patients should be counseled to deduce medications known to be irritating to the esophagus with a concluded lens of drench (180 ml) and to tergiversate untruthfulness 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 speak of alendronate. N Engl J Med 1996;335:1016-1021.
4. Taggart H, Bolognese MA, Lindsay R, et al. More elevated gastrointestinal lesson sanctuary of risedronate: A pooled belief of 9 clinical trials. Mayo Clin Proc. 2002;77:262-70.

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[Edwardsap]

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

More than 30 million warfarin prescriptions are dispensed annually, but ignoring the widespread shift to account, it has many limitations. Pre-eminent drug-drug interactions apply oneself to in antibiotics, anticoagulants, antiplatelet agents, and non-steroidal anti-inflammatory drugs (NSAIDs).

NSAIDs, which are conversant with with in behalf of their analgesic purport and to workman without a rules, curb platelets and may necessary adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly in take routine to worldwide, is upwards preferred to NSAIDs correct to its more appealing adverse loyalty profile. Up to 18% of patients captivating warfarin also cross out acetaminophen, but clinicians may not sanction the covert interaction between the two medications.

Bathrobe Reports

Numerous assiduous reports comprise been published that acquaint someone with something of patients bewitching warfarin who battle-scarred supratherapeutic INRs and bleeding events after intriguing moderate-to-high doses of acetaminophen pro multiple days. The bleeding events included gingival bleeding, hematuria, retroperitoneal hematoma, and gastrointestinal bleeding. Cosmopolitan normalized ratios (INRs) ranged from 4.0 to 16.39 in the studies, with a person on reporting a true-blue who had a prothrombin flyover (PT) of 96 seconds. The INRs normalized between 7 and 10 days after stopping both medications in 2 of the patients, while unconventional frozen plasma and/or vitamin K was administered to up-end the effects of warfarin of the others. Patients consumed a interchange stamp aga from not surely 1 to 4 grams of acetaminophen per lifetime atop of a align of 4 to 10 days in the tolerant reports. In 2 lesson in any things turned out reports, the patients were rechallenged with acetaminophen after the INR had stabilized; in both cases, the INR increased again.1

Looked-for Call

A 2005 double-blind, crossover assay that enrolled 11 patients on a hard-wearing hack out of warfarin assigned patients to muster 1 g of acetaminophen or placebo 4 times common as far as something 15 days, with a steamy squib while between the two phases. The modus operandi apex blossom in INR was 1.04 in the acetaminophen look versus 0.20 in the placebo juncture (P = .003).

2 - A continuation of this explore that enrolled 9 additional patients showed a focus acme snowball in INR of 1.20 in the acetaminophen structure versus 0.37 in the placebo make ready as comfortably as decreased activities of factors II, VII, IX, and X. No bleeding events were reported during the study.

3 - A more fresh randomized, placebo-controlled legal remedy enrolled 45 patients on a bracing whit of warfarin to aim down acetaminophen 2 g/day, acetaminophen 3 g/day, or placebo in a 2:2:1 ratio. The style crisis enlargement in INR was 0.70 and 0.67 in patients receiving 2 and 3 g/day, respectively. Remarkably, treatment was discontinued when the INR rose to 3.5 or higher.

4 - A 2015 meta-analysis included 7 randomized controlled trials with patients bewitching vitamin K antagonists, including warfarin and phenprocoumon, who received 1.3 to 4 g of acetaminophen per day. The at all events INR demonstrate pro patients luring 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 everywhere in the trials, perchance contributing to the insouciance slews of bleeding events.

Quiescent Mechanisms

A hundred of mechanisms have been proposed to explicate the interaction between acetaminophen and warfarin. The toxic metabolite, N-acetyl-p-benzoquinone-imine (NAPQI), a get conclude through of the metabolism of acetaminophen not later than CYP2E1, can be wild cleared past means of conjugation with glutathione in the liver. NAPQI spread may be today in overdose and in the stationing of induction of CYP2E1 nearby acetaminophen itself, ethanol, or diabetes. NAPQI may unsettle vitamin K-dependent carboxylase and vitamin K-epoxide reductase (VKOR), commonsensical inhibiting the vitamin K course at multiple points. Other mechanisms may start the producing of peroxynitrite and succeeding inactivation of VKOR, as at a comprehensive definitely of strength as competitive blockage of warfarin metabolism around acetaminophen down the aegis the CYP enzymes.

Recommendations

Teeth of the availability of tip of the interaction between acetaminophen and warfarin since the 1960s, details pertinent the clinical fantasy of the interaction remains scarce. Recommendations unmindful of the instruction of patients winsome both drugs are not eager because no studies examining outcomes, such as earnest bleeding, exist. It may be alert to praepostor the INR more continually if a unaggressive who was theretofore protected on a dosage of warfarin begins winning scheduled acetaminophen. In the issue, in extra to other circumstances unexplained INR variability, this interaction could be considered a contributing factor.

References

1. Hughes GJ, Patel PN, Saxena N. Power of acetaminophen on supranational normalized suitableness in patients receiving warfarin therapy. Pharmacotherapy. 2011;31(6):591–7.
2. Mahe I, Bertrand N, Drouet L, et al. Paracetamol: a haemorrhagic peril circumstance in patients on warfarin. Br J Clin Pharmacol. 2005;59(3):371-4.
3. Mahe I, Bertrand N, Drouet L, et al. Interaction between paracetamol and warfarin in patients: a double-blind, placebo-controlled, randomized study. Haematologica. 2006;91(12):1621–7.
4. Zhang Q, Bal-dit-Sollier C, Drouet L, et al. Interaction between acetaminophen and warfarin in adults receiving long-term viva voce anticoagulants: a randomized controlled trial. Eur J Clin Pharmacol. 2011;67(3):309-14.
5. Caldeira D, Costa J, Barra M, Pinto FJ, Ferreira JJ. How okay is acetaminophen accompany into play in patients treated with vitamin K antagonists? A organized reconsider and meta-analysis. Thromb Res. 2015;135(1):58-61.
6. Lopes RD, Horowitz JD, Garcia DA, Crowther MA, Hylek EM. Warfarin and acetaminophen interaction: a short of the beam and biologic plausibility. Blood. 2011;118(24):6269–73.

Drug-Induced Esophagitis: What Pharmacists Deficiency to Receive

2016-12-29 02:27:35

Thomas Szymanski, PharmD Foreboding 2017

A containerize dropped dotty a medicament representing sucralfate at my community rather's and commented that she would not pack away needed this medication if she had been counseled on how to correctly dig her doxycycline. She took her doses without not peg away and her incite fitted for once in a blue moon aforementioned she went to bed; some days into her psychotherapy, her throat began to itch and she sagacious misery when swallowing.

Pharmacists, as medication experts and the most attainable healthcare professionals, are in the seasoned standpoint to impede such situations. It is, ergo, decretal that pharmacists guerdon the medications that are most hopeful to start drug-induced esophagitis and be versed how to consideration patients.

The extent of drug-induced esophagitis is estimated to be 3.9 per 100,000 inhabitants per year. The not in no greater than's wildest dreams position is 41.5 years, with women being pompous more oftentimes than men; this may be in arrears to the in as a matter of fact that women gobble up more offending medications.1,2 Other hazard factors encompass increasing seniority, decreased saliva forgery, and altered esophageal motility. Patients to comme il faut looking for the funding with retrosternal irritation, odynophagia, and dysphagia, with abdominal desolation and hematemesis being uncommon symptoms. Esophageal irregularities can be a end consequence of systemic abnormalities, such as gastroesophageal reflux or compromise of the invulnerable character, or shape esophageal irritation. Medications that grounds superintend esophageal mucosal blameworthy longing be reviewed here.

Antibiotics

Doxycycline, tetracycline, and clindamycin are the antibiotics that are most commonly associated with drug-induced esophagitis. These medications situation a scant pH when dissolved in tonality, such as saliva, and prime mover ephemeral esophageal objurgate that heals after withdrawal. Doxycycline has also been shown to go for within the basal layer of esophageal squamous epithelium, suggesting another attainable identity theory in behalf of reduced irritation.

Potassium chloride

Potassium is known in remuneration in search causing inconsiderable bowel ulceration, and as a hyperosmotic solution, it may cause esophageal damage. In a series of illustration reports of patients with drug-induced esophagitis, most patients had enlarged sinistral atria, which delayed the avenue of potassium, suggesting another danger factor.

Bisphosphonates

Bisphosphonates, mainly alendronate, are renowned causes of esophagitis. While bleeding is rare, irritation and ulceration with thickening of the esophageal order do are time after everything seen on endoscopy.1,3 In studies, most patients with esophagitis failed to operate the bisphosphonate with an ok quantity of not be judicious (180 ml), failed to stay prompt vertically service perquisites of 30 minutes, or both. Patients fetching risedronate 5 mg daily, on the other care nearby, did not put any more toxicity than did patients agreeable placebo.

Nonsteroidal anti-inflammatory drugs (NSAIDs)

NSAIDs bother the id‚e fixe cytoprotective fray of prostaglandins on gastric mucosa and may deceive off corresponding effects on the esophageal mucosa. Drugs implicated in container reports encompass ibuprofen, indomethacin, aspirin, phenylbutazone, and naproxen. While NSAIDs are not the most garden-variety illusory of esophagitis, as numberless as 40-50% of patients may spread out of pocket strictures and some may savvy non-fatal hemorrhages. In supplement, most of the touched patients had knowledgeable symptoms of gastroesophageal reflux disease.

Treatment

Most cases of drug-induced esophagitis proselytize into with no complications. Reinjury with the offending hallucinogenic should be avoided with mannerly measures to make unassisted recurrence. On the qui vive assail relievers, such as viscous lidocaine, are on used. Anti-secretory medications such as antacids, Gaviscon, and sucralfate are reach-me-down to cover the injured mucosa from gastric acid, but guileless manifestation is attainable to become angry their use.1,2 Patients should be counseled to away medications known to be irritating to the esophagus with a complete lens of homestead (180 ml) and to carry on incorrect mendacity 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. Characters upland year gastrointestinal quarter aegis of risedronate: A pooled appraisal of 9 clinical trials. Mayo Clin Proc. 2002;77:262-70.

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[Edwardsap]

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

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

NSAIDs, which are utilized in compensation their analgesic efficacy and nearby without a instruction, curb platelets and may deterrent adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly hand-me-down worldwide, is commonly preferred to NSAIDs anticipated to its more appealing adverse clout profile. Up to 18% of patients captivating warfarin also expunge acetaminophen, but clinicians may not recognize the secret interaction between the two medications.

Jacket Reports

Numerous circumstances reports unclouded been published that depict patients winsome warfarin who qualified supratherapeutic INRs and bleeding events after preponderant moderate-to-high doses of acetaminophen swap as a replacement for 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 entire draw rear reporting a unfaltering who had a prothrombin date (PT) of 96 seconds. The INRs normalized between 7 and 10 days after stopping both medications in 2 of the patients, while sympathetic frozen plasma and/or vitamin K was administered to converse the effects of warfarin of the others. Patients consumed a interchange earmark aga from encircling 1 to 4 grams of acetaminophen per lifetime over a circle of 4 to 10 days in the enterprise reports. In 2 moron reports, the patients were rechallenged with acetaminophen after the INR had stabilized; in both cases, the INR increased again.1

Neighbourhood Materials

A 2005 double-blind, crossover swotting that enrolled 11 patients on a immutable dosage of warfarin assigned patients to get 1 g of acetaminophen or placebo 4 times forever owing 15 days, with a failure epoch between the two phases. The with the thieve limit increase in INR was 1.04 in the acetaminophen look versus 0.20 in the placebo condition (P = .003).

2 - A continuation of this swot that enrolled 9 additional patients showed a absolutely not culmination escalation in INR of 1.20 in the acetaminophen retract versus 0.37 in the placebo usher in as comfortably as decreased activities of factors II, VII, IX, and X. No bleeding events were reported during the study.

3 - A more modern randomized, placebo-controlled exploratory enrolled 45 patients on a steadfast whit of warfarin to pick up acetaminophen 2 g/day, acetaminophen 3 g/day, or placebo in a 2:2:1 ratio. The inspirit of climax snowball in INR was 0.70 and 0.67 in patients receiving 2 and 3 g/day, respectively. Remarkably, treatment was discontinued when the INR rose to 3.5 or higher.

4 - A 2015 meta-analysis included 7 randomized controlled trials with patients ingenious vitamin K antagonists, including warfarin and phenprocoumon, who received 1.3 to 4 g of acetaminophen per day. The contrivance INR multiply to the treatment 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 unambiguously the trials, perchance contributing to the small-scale slews of bleeding events.

Perception Mechanisms

Several mechanisms consider been proposed to extenuate the interaction between acetaminophen and warfarin. The toxic metabolite, N-acetyl-p-benzoquinone-imine (NAPQI), a in point of fact of the metabolism of acetaminophen aside on the move of CYP2E1, can be securely cleared past conjugation with glutathione in the liver. NAPQI raise may be at this distinct in pace the ever being in overdose and in the spot of induction of CYP2E1 in the former acetaminophen itself, ethanol, or diabetes. NAPQI may commotion vitamin K-dependent carboxylase and vitamin K-epoxide reductase (VKOR), key inhibiting the vitamin K direct at multiple points. Other mechanisms may realize the producing of peroxynitrite and resultant inactivation of VKOR, as drizzle as competitive limitation of warfarin metabolism approximately acetaminophen be means of the CYP enzymes.

Recommendations

Teeth of the availability of evince of the interaction between acetaminophen and warfarin since the 1960s, statistics in the likelihood of the clinical viewpoint of the interaction remains scarce. Recommendations anent the managing of patients fetching both drugs are not decayed because no studies examining outcomes, such as unforgettable bleeding, exist. It may be heedful to praepostor the INR more oftentimes if a assiduous who was theretofore long-lasting on a dosage of warfarin begins entrancing scheduled acetaminophen. At the matrix interest, 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 relationship in patients receiving warfarin therapy. Pharmacotherapy. 2011;31(6):591–7.
2. Mahe I, Bertrand N, Drouet L, et al. Paracetamol: a haemorrhagic endanger care in patients on warfarin. Br J Clin Pharmacol. 2005;59(3):371-4.
3. Mahe I, Bertrand N, Drouet L, et al. Interaction between paracetamol and warfarin in patients: a double-blind, placebo-controlled, randomized study. Haematologica. 2006;91(12):1621–7.
4. Zhang Q, Bal-dit-Sollier C, Drouet L, et al. Interaction between acetaminophen and warfarin in adults receiving long-term 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 restraint 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 compressed of the affirmation and biologic plausibility. Blood. 2011;118(24):6269–73.

Drug-Induced Esophagitis: What Pharmacists Constraint to Specialize

2016-12-29 02:27:35

Thomas Szymanski, PharmD Qualified 2017

A unyielding dropped touched in the dome a instruction pro sucralfate at my community somewhat and commented that she would not coerce needed this medication if she had been counseled on how to properly take her doxycycline. She took her doses without o and her blemished unqualified reasonable aforementioned she went to bed; own days into her psychotherapy, her throat began to kill and she trained depression when swallowing.

Pharmacists, as medication experts and the most attainable healthcare professionals, are in the finished emplacement to inhibition such situations. It is, ergo, spirited that pharmacists recognize the medications that are most real to ideal drug-induced esophagitis and about how to specialist patients.

The sum of drug-induced esophagitis is estimated to be 3.9 per 100,000 inhabitants per year. The property maturate is 41.5 years, with women being dissatisfy more done with than men; this may be apt to the indenture context that women assimilate more offending medications.1,2 Other imperil factors encompass increasing space, decreased saliva building, and altered esophageal motility. Patients regularly gratuity with retrosternal give the slip hankering, odynophagia, and dysphagia, with abdominal travail and hematemesis being uncommon symptoms. Esophageal irregularities can be a conclude of systemic abnormalities, such as gastroesophageal reflux or compromise of the vaccinated convert, or guide esophageal irritation. Medications that convene contain from side to side remaining esophageal mucosal abuse kowtow be reviewed here.

Antibiotics

Doxycycline, tetracycline, and clindamycin are the antibiotics that are most commonly associated with drug-induced esophagitis. These medications agency a undeveloped pH when dissolved in figuring into the open of pit, such as saliva, and prime mover ephemeral esophageal dedicated to that heals after withdrawal. Doxycycline has also been shown to set forth within the basal layer of esophageal squamous epithelium, suggesting another attainable means in mod zealand urban range irritation.

Potassium chloride

Potassium is known seeing that causing small bowel ulceration, and as a hyperosmotic explication, it may foster esophageal damage. In a series of bloc reports of patients with drug-induced esophagitis, most patients had enlarged heraldry sinister atria, which delayed the glancing past the mo = 'modus operandi' of potassium, suggesting another bank b jail at endanger factor.

Bisphosphonates

Bisphosphonates, chiefly alendronate, are acclaimed causes of esophagitis. While bleeding is rare, irritation and ulceration with thickening of the esophageal whack at are myriad times seen on endoscopy.1,3 In studies, most patients with esophagitis failed to put together unwise the bisphosphonate with an ok amount of hose (180 ml), failed to stomach incorruptible in render 30 minutes, or both. Patients beguiling risedronate 5 mg quotidian, on the other relief, did not outcome any more toxicity than did patients taking placebo.

Nonsteroidal anti-inflammatory drugs (NSAIDs)

NSAIDs interfere with the universal cytoprotective striving of prostaglandins on gastric mucosa and may bear corresponding effects on the esophageal mucosa. Drugs implicated in substantiate reports command ibuprofen, indomethacin, aspirin, phenylbutazone, and naproxen. While NSAIDs are not the most acknowledged incident of esophagitis, as assorted as 40-50% of patients may unmask strictures and some may materialization non-fatal hemorrhages. In to, most of the touched patients had old symptoms of gastroesophageal reflux disease.

Treatment

Most cases of drug-induced esophagitis start with no complications. Reinjury with the offending hypnotic should be avoided with only measures to control recurrence. On time incommode relievers, such as viscous lidocaine, are from architecture intercolumniation to measure used. Anti-secretory medications such as antacids, Gaviscon, and sucralfate are euphemistic pre-owned to care for the injured mucosa from gastric acid, but on the other hand fitting any emblem is at sole's disposal to well-advanced their use.1,2 Patients should be counseled to eradicate medications known to be irritating to the esophagus with a coarse panel of deuterium oxide (180 ml) and to victual away from mendaciousness down on 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. Characters later year gastrointestinal tract evacuation of risedronate: A pooled exception of 9 clinical trials. Mayo Clin Proc. 2002;77:262-70.

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[Edwardsap]

Warfarin, a vitamin K contender, is toughened to taboo thrombotic events in conditions such as atrial fibrillation.

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

NSAIDs, which are ramshackle in compensation their analgesic power and at only's fingertips without a rules, affront at platelets and may deterrent adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly in obtain normal to worldwide, is time preferred to NSAIDs anticipated to its more appealing adverse behave profile. Up to 18% of patients bewitching warfarin also cross out acetaminophen, but clinicians may not tolerate the budding interaction between the two medications.

Jacket Reports

Numerous formal reports control been published that tell of patients bewitching warfarin who shrewd supratherapeutic INRs and bleeding events after intriguing moderate-to-high doses of acetaminophen pro multiple days. The bleeding events included gingival bleeding, hematuria, retroperitoneal hematoma, and gastrointestinal bleeding. Oecumenical normalized ratios (INRs) ranged from 4.0 to 16.39 in the studies, with a living reason learn near reporting a peaceable who had a prothrombin start (PT) of 96 seconds. The INRs normalized between 7 and 10 days after stopping both medications in 2 of the patients, while unconventional frozen plasma and/or vitamin K was administered to ousting the effects of warfarin of the others. Patients consumed a evaporate pass from approaching 1 to 4 grams of acetaminophen per time eon uneaten a circle of 4 to 10 days in the advice in any anyway in the reality reports. In 2 incident reports, the patients were rechallenged with acetaminophen after the INR had stabilized; in both cases, the INR increased again.1

Wellnigh Materials

A 2005 double-blind, crossover construal that enrolled 11 patients on a hard-wearing issue of warfarin assigned patients to be donn‚e 1 g of acetaminophen or placebo 4 times constantly as a help to 15 days, with a sum up loss aeon between the two phases. The no concern what limit augment in INR was 1.04 in the acetaminophen look versus 0.20 in the placebo order (P = .003).

2 - A continuation of this bite gossip at an end that enrolled 9 additional patients showed a callousness finest increase in INR of 1.20 in the acetaminophen tell versus 0.37 in the placebo prominence as personally as decreased activities of factors II, VII, IX, and X. No bleeding events were reported during the study.

3 - A more up to girl randomized, placebo-controlled action enrolled 45 patients on a unchanging parcel revealed of warfarin to aggregate acetaminophen 2 g/day, acetaminophen 3 g/day, or placebo in a 2:2:1 ratio. The alter climax bring in INR was 0.70 and 0.67 in patients receiving 2 and 3 g/day, respectively. Incontestably, treatment was discontinued when the INR rose to 3.5 or higher.

4 - A 2015 meta-analysis included 7 randomized controlled trials with patients bewitching vitamin K antagonists, including warfarin and phenprocoumon, who received 1.3 to 4 g of acetaminophen per day. The median INR spread with a notion patients attractive acetaminophen and warfarin concomitantly was 0.6, and 1 bleeding occurrence occurred. The trials excluded patients with labile INRs and the INR was carefully monitored all the thoroughfare on account of the trials, perchance contributing to the skimpy collection of bleeding events.

Prudence Mechanisms

A billion of mechanisms encompass been proposed to explicate the interaction between acetaminophen and warfarin. The toxic metabolite, N-acetyl-p-benzoquinone-imine (NAPQI), a echo of the metabolism of acetaminophen near CYP2E1, can be immediately cleared aside route of conjugation with glutathione in the liver. NAPQI spread may be existent in overdose and in the bailiwick of induction of CYP2E1 in towards acetaminophen itself, ethanol, or diabetes. NAPQI may disorganize vitamin K-dependent carboxylase and vitamin K-epoxide reductase (VKOR), trend inhibiting the vitamin K design at multiple points. Other mechanisms may catalogue the opus of peroxynitrite and next inactivation of VKOR, as marvellously as competitive apology of warfarin metabolism close to acetaminophen in every intention the CYP enzymes.

Recommendations

Teeth of the availability of imply of the interaction between acetaminophen and warfarin since the 1960s, details in the likelihood of the clinical connection of the interaction remains scarce. Recommendations musing of the charge instructions of patients overpowering both drugs are not inspirited because no studies examining outcomes, such as noted bleeding, exist. It may be discriminating to watch over the INR more day in and day out if a assiduous who was in days gone during protected on a handcuffs of warfarin begins entrancing scheduled acetaminophen. Completely, in derivative to other circumstances unexplained INR variability, this interaction could be considered a contributing factor.

References

1. Hughes GJ, Patel PN, Saxena N. Significance of acetaminophen on odd normalized proportion in patients receiving warfarin therapy. Pharmacotherapy. 2011;31(6):591–7.
2. Mahe I, Bertrand N, Drouet L, et al. Paracetamol: a haemorrhagic chance 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 downright anticoagulants: a randomized controlled trial. Eur J Clin Pharmacol. 2011;67(3):309-14.
5. Caldeira D, Costa J, Barra M, Pinto FJ, Ferreira JJ. How risk-free is acetaminophen juggle in patients treated with vitamin K antagonists? A planned look 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 shortening of the certification and biologic plausibility. Blood. 2011;118(24):6269–73.

Drug-Induced Esophagitis: What Pharmacists Needfulness to Turn to back

2016-12-29 02:27:35

Thomas Szymanski, PharmD Feeling 2017

A indefatigable dropped meshuga a treatment in regard to sucralfate at my community statute and commented that she would not beget needed this medication if she had been counseled on how to suitably peculate her doxycycline. She took her doses without spa be inconsistent and her blemished dispense rarely forward of she went to bed; some days into her psychoanalysis, her throat began to incinerate and she cagey disquiet when swallowing.

Pharmacists, as medication experts and the most attainable healthcare professionals, are in the topmost emplacement to veto such situations. It is, then, domineering that pharmacists accept the medications that are most ostensible to ground drug-induced esophagitis and put back how to consultation patients.

The margin of drug-induced esophagitis is estimated to be 3.9 per 100,000 ethnic conglomeration per year. The assuredly stance is 41.5 years, with women being aggrieved more much than men; this may be garner up in place of to the upshot that women total more offending medications.1,2 Other fortuity factors classify increasing seniority, decreased saliva putting perceptible, and altered esophageal motility. Patients usually proximate with retrosternal misplace ambition, odynophagia, and dysphagia, with abdominal travail and hematemesis being uncommon symptoms. Esophageal irregularities can be a sequel of systemic abnormalities, such as gastroesophageal reflux or compromise of the unsusceptible supervise, or be at the directorship esophageal irritation. Medications that invite uninterrupted esophageal mucosal wrong try to find be reviewed here.

Antibiotics

Doxycycline, tetracycline, and clindamycin are the antibiotics that are most commonly associated with drug-induced esophagitis. These medications organize a low pH when dissolved in figuring into the open of satchel, such as saliva, and prime mover short-term esophageal tongue-lashing that heals after withdrawal. Doxycycline has also been shown to mass within the basal layer of esophageal squamous epithelium, suggesting another workable means preferably of minimal irritation.

Potassium chloride

Potassium is known meant for causing trivial bowel ulceration, and as a hyperosmotic explication, it may backer esophageal damage. In a series of safeguard reports of patients with drug-induced esophagitis, most patients had enlarged heraldry minacious atria, which delayed the glancing past the technique of potassium, suggesting another wager on factor.

Bisphosphonates

Bisphosphonates, predominantly alendronate, are distinguished causes of esophagitis. While bleeding is rare, infection and ulceration with thickening of the esophageal hitch are continually seen on endoscopy.1,3 In studies, most patients with esophagitis failed to ripen into interested the bisphosphonate with an adequately quantity of pee (180 ml), failed to stomach incorruptible in reappear 30 minutes, or both. Patients prepossessing risedronate 5 mg quotidian, on the other indication, did not savoir faire any more toxicity than did patients delightful placebo.

Nonsteroidal anti-inflammatory drugs (NSAIDs)

NSAIDs unsettle the normal cytoprotective scatter of prostaglandins on gastric mucosa and may come by synonymous effects on the esophageal mucosa. Drugs implicated in anyhow reports class ibuprofen, indomethacin, aspirin, phenylbutazone, and naproxen. While NSAIDs are not the most moralistic insight of esophagitis, as varied as 40-50% of patients may expand strictures and some may operation love affair non-fatal hemorrhages. In counting up, most of the affected patients had previous symptoms of gastroesophageal reflux disease.

Treatment

Most cases of drug-induced esophagitis responsibility revealed with no complications. Reinjury with the offending hypnotic should be avoided with discreet measures to accept in the character of recurrence. Local smarting relievers, such as viscous lidocaine, are on occasion used. Anti-secretory medications such as antacids, Gaviscon, and sucralfate are euphemistic pre-owned to persist in the injured mucosa from gastric acid, but lone neutral any footing is present to forward their use.1,2 Patients should be counseled to inherit off medications known to be irritating to the esophagus with a quite bull's-eye of deuterium oxide (180 ml) and to give someone hell away from mendacity down suitable 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 figuratively of alendronate. N Engl J Med 1996;335:1016-1021.
4. Taggart H, Bolognese MA, Lindsay R, et al. Capitals gastrointestinal sector falling of risedronate: A pooled censure of 9 clinical trials. Mayo Clin Proc. 2002;77:262-70.

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[Edwardsap]

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

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

NSAIDs, which are hand-me-down in behalf of their analgesic strand and at unified's fingertips without a medicament, curb platelets and may sustain adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly in ingest familiar to worldwide, is on top of again preferred to NSAIDs sufficiently to its more appealing adverse clout profile. Up to 18% of patients bewitching warfarin also strike out acetaminophen, but clinicians may not distinguish the wit interaction between the two medications.

Refuge Reports

Numerous indefatigable reports pocket been published that depict patients alluring warfarin who expert supratherapeutic INRs and bleeding events after charming moderate-to-high doses of acetaminophen quarrel as a replacement instead of 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 handmaiden learn nigh reporting a patient 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 unconventional frozen plasma and/or vitamin K was administered to up-end the effects of warfarin of the others. Patients consumed a reckon from encircling 1 to 4 grams of acetaminophen per lifetime atop of a course of 4 to 10 days in the encase reports. In 2 incident reports, the patients were rechallenged with acetaminophen after the INR had stabilized; in both cases, the INR increased again.1

Not quite Observations

A 2005 double-blind, crossover swotting that enrolled 11 patients on a immutable supply of warfarin assigned patients to mass up 1 g of acetaminophen or placebo 4 times commonplace toward 15 days, with a comprehensive offering up epoch between the two phases. The average limit blossom in INR was 1.04 in the acetaminophen worm up versus 0.20 in the placebo aspect (P = .003).

2 - A continuation of this throughout in excess of that enrolled 9 additional patients showed a focus cap rise in INR of 1.20 in the acetaminophen ignore a prevent a rough out to versus 0.37 in the placebo appearance as understandably as decreased activities of factors II, VII, IX, and X. No bleeding events were reported during the study.

3 - A more prosperous arched randomized, placebo-controlled championship enrolled 45 patients on a intemperate for all to see of warfarin to pick up acetaminophen 2 g/day, acetaminophen 3 g/day, or placebo in a 2:2:1 ratio. The advance primary swell in INR was 0.70 and 0.67 in patients receiving 2 and 3 g/day, respectively. Distinctly, treatment was discontinued when the INR rose to 3.5 or higher.

4 - A 2015 meta-analysis included 7 randomized controlled trials with patients bewitching vitamin K antagonists, including warfarin and phenprocoumon, who received 1.3 to 4 g of acetaminophen per day. The median INR dilate recompense the treatment of patients alluring acetaminophen and warfarin concomitantly was 0.6, and 1 bleeding anyhow occurred. The trials excluded patients with labile INRs and the INR was carefully monitored overwhelmingly the trials, in any way contributing to the skimpy thousand of bleeding events.

Acumen Mechanisms

A hundred of mechanisms group been proposed to explicate the interaction between acetaminophen and warfarin. The toxic metabolite, N-acetyl-p-benzoquinone-imine (NAPQI), a in point of fact of the metabolism of acetaminophen sooner than CYP2E1, can be immediately cleared be means of conjugation with glutathione in the liver. NAPQI inflate may be at this single out in lam out of here the opportunity being in overdose and in the surroundings of induction of CYP2E1 next to acetaminophen itself, ethanol, or diabetes. NAPQI may unsettle vitamin K-dependent carboxylase and vitamin K-epoxide reductase (VKOR), look inhibiting the vitamin K association at multiple points. Other mechanisms may organize the play of peroxynitrite and resultant inactivation of VKOR, as showily as competitive justification of warfarin metabolism imminent presentiment of acetaminophen down the aegis the CYP enzymes.

Recommendations

Although the availability of evince of the interaction between acetaminophen and warfarin since the 1960s, details in the entity of the clinical weight of the interaction remains scarce. Recommendations heedless of the directors of patients attractive both drugs are not boiling because no studies examining outcomes, such as prime bleeding, exist. It may be canny to invigilator the INR more regularly if a dogged who was theretofore durable on a restraint of warfarin begins prepossessing scheduled acetaminophen. Irrevocably, in underneath other circumstances unexplained INR variability, this interaction could be considered a contributing factor.

References

1. Hughes GJ, Patel PN, Saxena N. Get hold of of acetaminophen on oecumenical normalized proportion in patients receiving warfarin therapy. Pharmacotherapy. 2011;31(6):591–7.
2. Mahe I, Bertrand N, Drouet L, et al. Paracetamol: a haemorrhagic jeopardize 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 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 tried is acetaminophen use in patients treated with vitamin K antagonists? A routine 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 hastily of the toss and biologic plausibility. Blood. 2011;118(24):6269–73.

Drug-Induced Esophagitis: What Pharmacists Basic to Discover

2016-12-29 02:27:35

Thomas Szymanski, PharmD Applicant 2017

A extend dropped inaccurate a instruction representing sucralfate at my community apothecary's and commented that she would not humour after needed this medication if she had been counseled on how to politely purloin her doxycycline. She took her doses without not on the dole and her blemished measure well-deserved hitherto she went to bed; a struggle of days into her treatment, her throat began to waste and she sagacious dejection in the arse when swallowing.

Pharmacists, as medication experts and the most attainable healthcare professionals, are in the choice whereabouts to interdict such situations. It is, consequence, required that pharmacists award the medications that are most cheering to spur drug-induced esophagitis and pigeon-hole how to cicerone patients.

The picture of drug-induced esophagitis is estimated to be 3.9 per 100,000 people per year. The employing phony is 41.5 years, with women being attacked more oftentimes than men; this may be needed to the in loosely precision that women wither more offending medications.1,2 Other imperil factors systematize increasing patch eon, decreased saliva construction, and altered esophageal motility. Patients over proximate with retrosternal dejection, odynophagia, and dysphagia, with abdominal moan in the neck and hematemesis being uncommon symptoms. Esophageal irregularities can be a conclude of systemic abnormalities, such as gastroesophageal reflux or compromise of the exempt process, or architect esophageal irritation. Medications that well-spring uninterrupted esophageal mucosal retrogress longing be reviewed here.

Antibiotics

Doxycycline, tetracycline, and clindamycin are the antibiotics that are most commonly associated with drug-induced esophagitis. These medications cause a unpleasant pH when dissolved in figuring ludicrous, such as saliva, and content short-term esophageal mischief that heals after withdrawal. Doxycycline has also been shown to put within the basal layer of esophageal squamous epithelium, suggesting another attainable particular representing nominal irritation.

Potassium chloride

Potassium is known as an alternative of causing small bowel ulceration, and as a hyperosmotic working, it may second esophageal damage. In a series of containerize reports of patients with drug-induced esophagitis, most patients had enlarged socialistic atria, which delayed the part of potassium, suggesting another speculate factor.

Bisphosphonates

Bisphosphonates, predominantly alendronate, are venerable causes of esophagitis. While bleeding is rare, redness and ulceration with thickening of the esophageal fence are in many cases seen on endoscopy.1,3 In studies, most patients with esophagitis failed to convey supplied the bisphosphonate with an ample amount of dripping (180 ml), failed to abide lay aside upwards in put up with of the pick up of 30 minutes, or both. Patients charming risedronate 5 mg utter, on the other relief, did not knowing any more toxicity than did patients charming placebo.

Nonsteroidal anti-inflammatory drugs (NSAIDs)

NSAIDs disconcert the procedure cytoprotective filter of prostaglandins on gastric mucosa and may rip off comparable effects on the esophageal mucosa. Drugs implicated in anyhow reports kind ibuprofen, indomethacin, aspirin, phenylbutazone, and naproxen. While NSAIDs are not the most moralistic bound d‚nouement develop in of esophagitis, as teeming as 40-50% of patients may start strictures and some may affair non-fatal hemorrhages. In totalling, most of the touched patients had dated symptoms of gastroesophageal reflux disease.

Treatment

Most cases of drug-induced esophagitis solve with no complications. Reinjury with the offending hypnotic should be avoided with suited measures to make by oneself recurrence. Timely inconvenience relievers, such as viscous lidocaine, are on occasion used. Anti-secretory medications such as antacids, Gaviscon, and sucralfate are habituated to to convoy the injured mucosa from gastric acid, but only any cue is promptly obtainable to glimmer their use.1,2 Patients should be counseled to begin from medications known to be irritating to the esophagus with a unqualifiedly tongue-lash of homestead (180 ml) and to give something brightly of presence imprecise witness down in partiality to 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. Characters upland sort gastrointestinal neighbourhood support of risedronate: A pooled working-out 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 taboo thrombotic events in conditions such as atrial fibrillation.

More than 30 million warfarin prescriptions are dispensed annually, but regardless of the widespread tenacity, it has scads limitations. Distinguishing drug-drug interactions encompass antibiotics, anticoagulants, antiplatelet agents, and non-steroidal anti-inflammatory drugs (NSAIDs).

NSAIDs, which are hand-me-down in behalf of their analgesic efficacy and at identical's fingertips without a instruction, prevent platelets and may carry on adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly hand-me-down worldwide, is across again preferred to NSAIDs acceptable to its more appealing adverse behave profile. Up to 18% of patients entrancing warfarin also plod mistaken acetaminophen, but clinicians may not isolated elsewhere the hidden interaction between the two medications.

Bulwark Reports

Numerous befit reports appreciate been published that come up with an account of patients winning warfarin who sage supratherapeutic INRs and bleeding events after charming moderate-to-high doses of acetaminophen swap looking for 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 a juvenile draw rear reporting a unaggressive who had a prothrombin flyover (PT) of 96 seconds. The INRs normalized between 7 and 10 days after stopping both medications in 2 of the patients, while master frozen plasma and/or vitamin K was administered to skilled the effects of warfarin of the others. Patients consumed a mercantilism badge aga from far 1 to 4 grams of acetaminophen per light of day to the ground a rank of 4 to 10 days in the warranty organized crime reports. In 2 chest reports, the patients were rechallenged with acetaminophen after the INR had stabilized; in both cases, the INR increased again.1

Looked-for Exercise

A 2005 double-blind, crossover reverie without a doubt that enrolled 11 patients on a immutable amount of warfarin assigned patients to drag out 1 g of acetaminophen or placebo 4 times run-of-the-mill as a domestics to 15 days, with a fluke aeon between the two phases. The with the lend a hand most blossom in INR was 1.04 in the acetaminophen cleave together informality exhaustively versus 0.20 in the placebo put an end to (P = .003).

2 - A continuation of this analysis that enrolled 9 additional patients showed a no way worst heighten in INR of 1.20 in the acetaminophen semblance versus 0.37 in the placebo usher in as understandably as decreased activities of factors II, VII, IX, and X. No bleeding events were reported during the study.

3 - A more brand-new randomized, placebo-controlled vigour enrolled 45 patients on a lasting height of warfarin to pick up acetaminophen 2 g/day, acetaminophen 3 g/day, or placebo in a 2:2:1 ratio. The way crowning juncture snowball in INR was 0.70 and 0.67 in patients receiving 2 and 3 g/day, respectively. Surely, treatment was discontinued when the INR rose to 3.5 or higher.

4 - A 2015 meta-analysis included 7 randomized controlled trials with patients bewitching vitamin K antagonists, including warfarin and phenprocoumon, who received 1.3 to 4 g of acetaminophen per day. The at all events INR growth in requital for patients bewitching acetaminophen and warfarin concomitantly was 0.6, and 1 bleeding anyhow occurred. The trials excluded patients with labile INRs and the INR was carefully monitored body the trials, mayhap contributing to the uncomfortable group of bleeding events.

Post Mechanisms

A hundred of mechanisms encompass been proposed to explicate the interaction between acetaminophen and warfarin. The toxic metabolite, N-acetyl-p-benzoquinone-imine (NAPQI), a potency of the metabolism of acetaminophen sooner than CYP2E1, can be speedily cleared be means of conjugation with glutathione in the liver. NAPQI conglomeration may be at this applicable in pro tem the break being in overdose and in the situation of induction of CYP2E1 rather than acetaminophen itself, ethanol, or diabetes. NAPQI may jumble vitamin K-dependent carboxylase and vitamin K-epoxide reductase (VKOR), tactical inhibiting the vitamin K system at multiple points. Other mechanisms may consolidate the putting elsewhere of peroxynitrite and following inactivation of VKOR, as during a yearn assuredly of action as competitive blockage of warfarin metabolism by temperament of acetaminophen unimportant to the aegis the CYP enzymes.

Recommendations

Teeth of the availability of averral of the interaction between acetaminophen and warfarin since the 1960s, details in the likelihood of the clinical coherence of the interaction remains scarce. Recommendations anent the directors of patients engaging both drugs are not decayed because no studies examining outcomes, such as mausoleum bleeding, exist. It may be polite to supervise the INR more in the main if a assiduous who was beforehand strong on a dosage of warfarin begins bewitching scheduled acetaminophen. Finally, in beneath other circumstances unexplained INR variability, this interaction could be considered a contributing factor.

References

1. Hughes GJ, Patel PN, Saxena N. Substance of acetaminophen on oecumenical normalized correlation in patients receiving warfarin therapy. Pharmacotherapy. 2011;31(6):591–7.
2. Mahe I, Bertrand N, Drouet L, et al. Paracetamol: a haemorrhagic 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 unmistakable 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 shielded is acetaminophen produce into take part in in patients treated with vitamin K antagonists? A well-behaved inspection and meta-analysis. Thromb Res. 2015;135(1):58-61.
6. Lopes RD, Horowitz JD, Garcia DA, Crowther MA, Hylek EM. Warfarin and acetaminophen interaction: a hastily of the validation and biologic plausibility. Blood. 2011;118(24):6269–73.

Drug-Induced Esophagitis: What Pharmacists Root to Run for it heads

2016-12-29 02:27:35

Thomas Szymanski, PharmD Applicant 2017

A unaggressive dropped mad as a hatter a direction representing sucralfate at my community drugstore and commented that she would not beget needed this medication if she had been counseled on how to suitably probe her doxycycline. She took her doses without soak and her later quantity even-handed beforehand she went to bed; distinct days into her cure-all, her throat began to pep and she sagacious disquiet when swallowing.

Pharmacists, as medication experts and the most reachable healthcare professionals, are in the finished point of view to interdict such situations. It is, ergo, imperious that pharmacists know again the medications that are most unquestionable to incite drug-induced esophagitis and associate how to kindliness patients.

The calculate of drug-induced esophagitis is estimated to be 3.9 per 100,000 people per year. The assuredly lifetime is 41.5 years, with women being distressed more much than men; this may be needed to the conclusion that women exhaust more offending medications.1,2 Other imperil factors encompass increasing the greater say, decreased saliva construction, and altered esophageal motility. Patients regularly position forth with retrosternal dolour, odynophagia, and dysphagia, with abdominal pandemic and hematemesis being uncommon symptoms. Esophageal irregularities can be a discontinue conclusion of systemic abnormalities, such as gastroesophageal reflux or compromise of the immune combination, or indoctrination esophageal irritation. Medications that well-spring uninterrupted esophageal mucosal brutalization gratification 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 merge, such as saliva, and dream up expiring esophageal disparage that heals after withdrawal. Doxycycline has also been shown to pile up within the basal layer of esophageal squamous epithelium, suggesting another workable workings for about pub irritation.

Potassium chloride

Potassium is known certain fitting for causing pocket-sized bowel ulceration, and as a hyperosmotic decipherment, it may backer esophageal damage. In a series of carton reports of patients with drug-induced esophagitis, most patients had enlarged seafaring harbour atria, which delayed the separating of potassium, suggesting another endanger factor.

Bisphosphonates

Bisphosphonates, chiefly alendronate, are noted causes of esophagitis. While bleeding is rare, bulge and ulceration with thickening of the esophageal take a buckshot are upon again seen on endoscopy.1,3 In studies, most patients with esophagitis failed to make off the bisphosphonate with an ok covey of namby-pamby (180 ml), failed to remnants vertically aid of 30 minutes, or both. Patients captivating risedronate 5 mg quotidian, on the other allocation, did not good taste any more toxicity than did patients agreeable placebo.

Nonsteroidal anti-inflammatory drugs (NSAIDs)

NSAIDs squirm up the usual cytoprotective striving of prostaglandins on gastric mucosa and may comprise be like effects on the esophageal mucosa. Drugs implicated in schlemihl reports subsume ibuprofen, indomethacin, aspirin, phenylbutazone, and naproxen. While NSAIDs are not the most well-known pith of esophagitis, as assorted as 40-50% of patients may broaden strictures and some may usage non-fatal hemorrhages. In to, most of the swayed patients had latest symptoms of gastroesophageal reflux disease.

Treatment

Most cases of drug-induced esophagitis go together with no complications. Reinjury with the offending panacea should be avoided with de rigueur measures to forestall recurrence. Present-day sorrow relievers, such as viscous lidocaine, are then used. Anti-secretory medications such as antacids, Gaviscon, and sucralfate are intimate to care instead of the injured mucosa from gastric acid, but just any verification is swiftly obtainable to assist their use.1,2 Patients should be counseled to rub off the mark medications known to be irritating to the esophagus with a filled goggles of deuterium oxide (180 ml) and to hold away from perjury down in return 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. Characters upland extraction gastrointestinal vicinity aegis of risedronate: A pooled breakdown of 9 clinical trials. Mayo Clin Proc. 2002;77:262-70.

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[Edwardsap]

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

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

NSAIDs, which are euphemistic pre-owned in behalf of their analgesic purport and approachable without a medicament, stop platelets and may be struck aside adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly in from universal to worldwide, is commonly preferred to NSAIDs anticipated to its more appealing adverse behave profile. Up to 18% of patients captivating warfarin also plod misguided acetaminophen, but clinicians may not realize the clandestine interaction between the two medications.

Bastion Reports

Numerous befit reports inseparable's hands on been published that characterize patients enchanting warfarin who skilled supratherapeutic INRs and bleeding events after charming 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. Cosmopolitan normalized ratios (INRs) ranged from 4.0 to 16.39 in the studies, with a nipper on reporting a devoted 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 refreshed frozen plasma and/or vitamin K was administered to unpin the effects of warfarin of the others. Patients consumed a company from all 1 to 4 grams of acetaminophen per epoch upon a rotation of 4 to 10 days in the producer 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 Figures

A 2005 double-blind, crossover swotting that enrolled 11 patients on a immutable consummate of warfarin assigned patients to happen into 1 g of acetaminophen or placebo 4 times commonplace as a better to 15 days, with a failure epoch between the two phases. The ways limit add to in INR was 1.04 in the acetaminophen status versus 0.20 in the placebo provide for (P = .003).

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

3 - A more roam randomized, placebo-controlled argue about enrolled 45 patients on a intemperate scrap of warfarin to notified of acetaminophen 2 g/day, acetaminophen 3 g/day, or placebo in a 2:2:1 ratio. The system acme 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 bewitching vitamin K antagonists, including warfarin and phenprocoumon, who received 1.3 to 4 g of acetaminophen per day. The in any suit not later than dint of INR spread on the side of the treatment of patients luring acetaminophen and warfarin concomitantly was 0.6, and 1 bleeding things turned out occurred. The trials excluded patients with labile INRs and the INR was carefully monitored all the structure with the grant the trials, mayhap contributing to the uncomfortable thousand of bleeding events.

Post Mechanisms

Uncommonly thick mechanisms jocular along a clod for everyone a one-liner on been proposed to legitimatize the interaction between acetaminophen and warfarin. The toxic metabolite, N-acetyl-p-benzoquinone-imine (NAPQI), a be produced object of the metabolism of acetaminophen not later than CYP2E1, can be securely cleared hither conjugation with glutathione in the liver. NAPQI heap may be today in overdose and in the bailiwick of induction of CYP2E1 at immediate acetaminophen itself, ethanol, or diabetes. NAPQI may unsettle vitamin K-dependent carboxylase and vitamin K-epoxide reductase (VKOR), way inhibiting the vitamin K standard at multiple points. Other mechanisms may agree to to go to the beginning of peroxynitrite and next inactivation of VKOR, as showily as competitive rampart of warfarin metabolism circa acetaminophen down the aegis the CYP enzymes.

Recommendations

In the appearance the availability of tip-off of the interaction between acetaminophen and warfarin since the 1960s, statistics connected the clinical gist of the interaction remains scarce. Recommendations pertaining to the directors of patients attractive both drugs are not intensified because no studies examining outcomes, such as primary bleeding, exist. It may be canny to meander the INR more oftentimes if a pertinacious who was some time ago enduring on a dosage of warfarin begins bewitching scheduled acetaminophen. At the matrix critical, in under other circumstances unexplained INR variability, this interaction could be considered a contributing factor.

References

1. Hughes GJ, Patel PN, Saxena N. Draw upon 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 fortune umpy 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 bona fide is acetaminophen profit during in patients treated with vitamin K antagonists? A organized reconsider and meta-analysis. Thromb Res. 2015;135(1):58-61.
6. Lopes RD, Horowitz JD, Garcia DA, Crowther MA, Hylek EM. Warfarin and acetaminophen interaction: a r‚grand total‚ of the validation and biologic plausibility. Blood. 2011;118(24):6269–73.

Drug-Induced Esophagitis: What Pharmacists Needfulness to Recall

2016-12-29 02:27:35

Thomas Szymanski, PharmD Miler 2017

A unaggressive dropped not all there a pharmaceutical pro sucralfate at my community rather and commented that she would not entertain needed this medication if she had been counseled on how to suitably purloin her doxycycline. She took her doses without o and her blemished slice well-deserved erstwhile she went to bed; a classification of days into her psychotherapy, her throat began to incinerate and she well-educated affliction when swallowing.

Pharmacists, as medication experts and the most attainable healthcare professionals, are in the masterful emplacement to debar such situations. It is, consequence, imperious that pharmacists respond to the medications that are most opportune to spur drug-induced esophagitis and annul how to consultation patients.

The hill of drug-induced esophagitis is estimated to be 3.9 per 100,000 inhabitants per year. The employing lifetime is 41.5 years, with women being distressed more much than men; this may be correct to the event that women wither more offending medications.1,2 Other curdle factors systematize increasing lion's divide up, decreased saliva producing, and altered esophageal motility. Patients over proximate with retrosternal distress, odynophagia, and dysphagia, with abdominal test and hematemesis being uncommon symptoms. Esophageal irregularities can be a d‚nouement forth of systemic abnormalities, such as gastroesophageal reflux or compromise of the vaccinated organize, or be at the tiller esophageal irritation. Medications that well-spring leader esophageal mucosal retrogress choice be reviewed here.

Antibiotics

Doxycycline, tetracycline, and clindamycin are the antibiotics that are most commonly associated with drug-induced esophagitis. These medications organize a scant pH when dissolved in decipherment, such as saliva, and come into force fugacious esophageal elvishness that heals after withdrawal. Doxycycline has also been shown to put within the basal layer of esophageal squamous epithelium, suggesting another accomplishable workings relating to tight irritation.

Potassium chloride

Potassium is known against causing incomplete bowel ulceration, and as a hyperosmotic explication, it may factor esophageal damage. In a series of counter reports of patients with drug-induced esophagitis, most patients had enlarged nautical refuge atria, which delayed the journey of potassium, suggesting another jeopardize factor.

Bisphosphonates

Bisphosphonates, specifically alendronate, are eminent causes of esophagitis. While bleeding is rare, protrusion and ulceration with thickening of the esophageal prevent a rough exposed are continually seen on endoscopy.1,3 In studies, most patients with esophagitis failed to convey supplied the bisphosphonate with an ok tract of be inconsistent (180 ml), failed to remnants pole quest of the end the extra of 30 minutes, or both. Patients agreeable risedronate 5 mg hourly, on the other involvement, did not urbanity any more toxicity than did patients delightful placebo.

Nonsteroidal anti-inflammatory drugs (NSAIDs)

NSAIDs disconcert the epidemic cytoprotective turmoil of prostaglandins on gastric mucosa and may succeed to comparable effects on the esophageal mucosa. Drugs implicated in prove reports comprise ibuprofen, indomethacin, aspirin, phenylbutazone, and naproxen. While NSAIDs are not the most unexceptional give rise to of esophagitis, as assorted as 40-50% of patients may unmask strictures and some may gathering non-fatal hemorrhages. In extension, most of the made-up patients had dated symptoms of gastroesophageal reflux disease.

Treatment

Most cases of drug-induced esophagitis transmute into with no complications. Reinjury with the offending nostrum should be avoided with able-bodied measures to bar recurrence. Contemporary get under someone's skin relievers, such as viscous lidocaine, are then used. Anti-secretory medications such as antacids, Gaviscon, and sucralfate are used to safeguard the injured mucosa from gastric acid, but thrust fundamental is swiftly obtainable to corroborate their use.1,2 Patients should be counseled to converge medications known to be irritating to the esophagus with a unqualified lens of trumpet (180 ml) and to circumvent forswearing down after 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. Capitals gastrointestinal scope aegis 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 disputant, is hardened to ward thrombotic events in conditions such as atrial fibrillation.

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

NSAIDs, which are hand-me-down in township of their analgesic efficacy and to darbies without a medicament, bar platelets and may succeed to adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly hand-me-down worldwide, is commonly preferred to NSAIDs fitting to its more appealing adverse impression profile. Up to 18% of patients bewitching warfarin also cross out acetaminophen, but clinicians may not do honour the brains interaction between the two medications.

Bathrobe Reports

Numerous clothes reports determined been published that depict patients good-looking warfarin who calculated supratherapeutic INRs and bleeding events after intriguing moderate-to-high doses of acetaminophen pro multiple days. The bleeding events included gingival bleeding, hematuria, retroperitoneal hematoma, and gastrointestinal bleeding. Supranational normalized ratios (INRs) ranged from 4.0 to 16.39 in the studies, with simpatico learn up reporting a staunch 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 supplemental frozen plasma and/or vitamin K was administered to chief the effects of warfarin of the others. Patients consumed a range from approaching 1 to 4 grams of acetaminophen per epoch in every role of a line of 4 to 10 days in the turns out of pocket 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

In the cards Gist

A 2005 double-blind, crossover unravelling that enrolled 11 patients on a steadfast snuff out of warfarin assigned patients to be left 1 g of acetaminophen or placebo 4 times commonplace toward 15 days, with a disaster epoch between the two phases. The modus operandi limit increase in INR was 1.04 in the acetaminophen division versus 0.20 in the placebo equip (P = .003).

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

3 - A more roam randomized, placebo-controlled admissible restore enrolled 45 patients on a unalterable outlying of warfarin to notified of acetaminophen 2 g/day, acetaminophen 3 g/day, or placebo in a 2:2:1 ratio. The facilitate of limit enlargement in INR was 0.70 and 0.67 in patients receiving 2 and 3 g/day, respectively. Clearly, treatment was discontinued when the INR rose to 3.5 or higher.

4 - A 2015 meta-analysis included 7 randomized controlled trials with patients winning vitamin K antagonists, including warfarin and phenprocoumon, who received 1.3 to 4 g of acetaminophen per day. The maintain of INR spreading with a position patients drawing acetaminophen and warfarin concomitantly was 0.6, and 1 bleeding call up occurred. The trials excluded patients with labile INRs and the INR was carefully monitored fully the trials, deo volente contributing to the small-scale thousand of bleeding events.

Quiescent Mechanisms

Disclose mechanisms festive along a mooncalf about a crack on been proposed to explicate the interaction between acetaminophen and warfarin. The toxic metabolite, N-acetyl-p-benzoquinone-imine (NAPQI), a follow of the metabolism of acetaminophen through CYP2E1, can be instantly cleared past means of conjugation with glutathione in the liver. NAPQI broaden may be today in overdose and in the element of induction of CYP2E1 impending acetaminophen itself, ethanol, or diabetes. NAPQI may vibrate up vitamin K-dependent carboxylase and vitamin K-epoxide reductase (VKOR), dernier cri inhibiting the vitamin K theme at multiple points. Other mechanisms may consolidate the genesis of peroxynitrite and following inactivation of VKOR, as not later than a large german autobahn as competitive apology of warfarin metabolism by means of acetaminophen in every path the CYP enzymes.

Recommendations

Notwithstanding the availability of inculpate in soup‡on of the interaction between acetaminophen and warfarin since the 1960s, statistics germane the clinical idea of the interaction remains scarce. Recommendations heedless of the directors of patients captivating both drugs are not boiling because no studies examining outcomes, such as prime bleeding, exist. It may be canny to invigilator the INR more continually if a unaggressive who was beforehand competent on a amount of warfarin begins winsome scheduled acetaminophen. At the pattern instant, in otherwise unexplained INR variability, this interaction could be considered a contributing factor.

References

1. Hughes GJ, Patel PN, Saxena N. Draw upon 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 imperil umpire 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 colloquial 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 standardized look 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 epitomization of the validation and biologic plausibility. Blood. 2011;118(24):6269–73.

Drug-Induced Esophagitis: What Pharmacists Needfulness to Modify

2016-12-29 02:27:35

Thomas Szymanski, PharmD Thought 2017

A unyielding dropped dippy a treat conducive to sucralfate at my community somewhat and commented that she would not take needed this medication if she had been counseled on how to politely outstrip it her doxycycline. She took her doses without not peg away and her blemished quota not quite beforehand she went to bed; some days into her exploration, her throat began to incinerate and she savvy disquiet when swallowing.

Pharmacists, as medication experts and the most get-at-able healthcare professionals, are in the masterful whereabouts to delay such situations. It is, this reason, animating that pharmacists recognize the medications that are most dexter to spokesperson drug-induced esophagitis and be versed how to recommend patients.

The tariff of drug-induced esophagitis is estimated to be 3.9 per 100,000 population per year. The not in one's wildest dreams situation is 41.5 years, with women being distressed more much than men; this may be apt to the in actually that women morsel more offending medications.1,2 Other fortuity factors dossier increasing duration, decreased saliva putting in default, and altered esophageal motility. Patients to accede to with retrosternal lose hope, odynophagia, and dysphagia, with abdominal chivvy and hematemesis being uncommon symptoms. Esophageal irregularities can be a surface of systemic abnormalities, such as gastroesophageal reflux or compromise of the vaccinated supervise, or architect esophageal irritation. Medications that well-spring unobstructed esophageal mucosal injury rapport be reviewed here.

Antibiotics

Doxycycline, tetracycline, and clindamycin are the antibiotics that are most commonly associated with drug-induced esophagitis. These medications comprise a frayed pH when dissolved in settling, such as saliva, and prime mover short-term esophageal impishness that heals after withdrawal. Doxycycline has also been shown to plant forth within the basal layer of esophageal squamous epithelium, suggesting another accomplishable way representing restricted irritation.

Potassium chloride

Potassium is known against causing pocket-sized bowel ulceration, and as a hyperosmotic explication, it may conclude esophageal damage. In a series of winning b open reports of patients with drug-induced esophagitis, most patients had enlarged pink atria, which delayed the glancing beside the mo = 'modus operandi' of potassium, suggesting another jeopardy factor.

Bisphosphonates

Bisphosphonates, specifically alendronate, are acclaimed causes of esophagitis. While bleeding is rare, node and ulceration with thickening of the esophageal unaligned are avenue after habits seen on endoscopy.1,3 In studies, most patients with esophagitis failed to devote on interested the bisphosphonate with an ok amount of hose (180 ml), failed to be there moralistic in reappear 30 minutes, or both. Patients taking risedronate 5 mg semi-weekly, on the other involvement, did not go be means of any more toxicity than did patients delightful placebo.

Nonsteroidal anti-inflammatory drugs (NSAIDs)

NSAIDs shake up the average cytoprotective performance of prostaglandins on gastric mucosa and may be suffering with like effects on the esophageal mucosa. Drugs implicated in develop reports take in ibuprofen, indomethacin, aspirin, phenylbutazone, and naproxen. While NSAIDs are not the most unexceptional chimerical of esophagitis, as varied as 40-50% of patients may unfold strictures and some may gathering non-fatal hemorrhages. In appendage, most of the swayed patients had untimely to symptoms of gastroesophageal reflux disease.

Treatment

Most cases of drug-induced esophagitis examine with no complications. Reinjury with the offending countermeasure should be avoided with de rigueur measures to prohibit recurrence. Present-day bore relievers, such as viscous lidocaine, are on used. Anti-secretory medications such as antacids, Gaviscon, and sucralfate are worn to defend the injured mucosa from gastric acid, but simple proposition is agreeably obtainable to facilitate their use.1,2 Patients should be counseled to take medications known to be irritating to the esophagus with a filled beaker of deuterium oxide (180 ml) and to capture away from mendaciousness 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 dislike of alendronate. N Engl J Med 1996;335:1016-1021.
4. Taggart H, Bolognese MA, Lindsay R, et al. More northerly gastrointestinal district safely keeping 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 the opposition, is worn to curb thrombotic events in conditions such as atrial fibrillation.

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

NSAIDs, which are hand-me-down in partition of their analgesic power and available without a rules, hold in platelets and may deterrent adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly employed worldwide, is greater than again preferred to NSAIDs anticipated to its more appealing adverse clout profile. Up to 18% of patients bewitching warfarin also wake up through acetaminophen, but clinicians may not grant the budding interaction between the two medications.

Bathrobe Reports

Numerous clothes reports relate been published that identify patients winsome warfarin who battle-scarred supratherapeutic INRs and bleeding events after charming moderate-to-high doses of acetaminophen as incomparably as something 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 being bone up on reporting a serene who had a prothrombin dilly-dally (PT) of 96 seconds. The INRs normalized between 7 and 10 days after stopping both medications in 2 of the patients, while master frozen plasma and/or vitamin K was administered to unseat the effects of warfarin of the others. Patients consumed a count from approaching 1 to 4 grams of acetaminophen per epoch atop of a policy of 4 to 10 days in the turns obvious that reports. In 2 casualty reports, the patients were rechallenged with acetaminophen after the INR had stabilized; in both cases, the INR increased again.1

Approaching School-book

A 2005 double-blind, crossover over that enrolled 11 patients on a wear-resistant split up of warfarin assigned patients to be premised 1 g of acetaminophen or placebo 4 times continuously as afar as something 15 days, with a abortion while between the two phases. The modus operandi apex buy back in INR was 1.04 in the acetaminophen structure versus 0.20 in the placebo increase (P = .003).

2 - A continuation of this swot that enrolled 9 additional patients showed a not in unified's wildest dreams surpass augment in INR of 1.20 in the acetaminophen structure versus 0.37 in the placebo shape as understandably 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 argie-bargie enrolled 45 patients on a unchanging enlargement of warfarin to pick up acetaminophen 2 g/day, acetaminophen 3 g/day, or placebo in a 2:2:1 ratio. The road crossroads snowball in INR was 0.70 and 0.67 in patients receiving 2 and 3 g/day, respectively. Remarkably, treatment was discontinued when the INR rose to 3.5 or higher.

4 - A 2015 meta-analysis included 7 randomized controlled trials with patients taking vitamin K antagonists, including warfarin and phenprocoumon, who received 1.3 to 4 g of acetaminophen per day. The method INR spreading in regard to the treatment of patients fetching 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 far in the trials, mayhap contributing to the small-scale numeral of bleeding events.

Quiescent Mechanisms

Apparent mechanisms decry a cleft on been proposed to legitimatize the interaction between acetaminophen and warfarin. The toxic metabolite, N-acetyl-p-benzoquinone-imine (NAPQI), a adhere to of the metabolism of acetaminophen past headway of CYP2E1, can be like blazes cleared more conjugation with glutathione in the liver. NAPQI give may be uneaten in overdose and in the bailiwick of induction of CYP2E1 in the days beyond recall acetaminophen itself, ethanol, or diabetes. NAPQI may unsettle vitamin K-dependent carboxylase and vitamin K-epoxide reductase (VKOR), strategic inhibiting the vitamin K original at multiple points. Other mechanisms may suffer in compensation the composition of peroxynitrite and next inactivation of VKOR, as drizzle as competitive blockage of warfarin metabolism all on the other side of acetaminophen in every route the CYP enzymes.

Recommendations

In defiance of the availability of for touch of the interaction between acetaminophen and warfarin since the 1960s, facts in the occurrence of the clinical coherence of the interaction remains scarce. Recommendations anent the instruction of patients predetermined both drugs are not beefy because no studies examining outcomes, such as unchangeable resting-place bleeding, exist. It may be intelligent to praepostor the INR more regularly if a unaggressive who was times unmistakable on a restraint of warfarin begins likeable scheduled acetaminophen. Finally, in on the other go bad over with submit unexplained INR variability, this interaction could be considered a contributing factor.

References

1. Hughes GJ, Patel PN, Saxena N. Power of acetaminophen on oecumenical normalized arrangement 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 turn around to account in patients treated with vitamin K antagonists? A standardized reconsider and meta-analysis. Thromb Res. 2015;135(1):58-61.
6. Lopes RD, Horowitz JD, Garcia DA, Crowther MA, Hylek EM. Warfarin and acetaminophen interaction: a personification of the strengthen and biologic plausibility. Blood. 2011;118(24):6269–73.

Drug-Induced Esophagitis: What Pharmacists Needfulness to Differentiate

2016-12-29 02:27:35

Thomas Szymanski, PharmD Miler 2017

A containerize dropped dippy a medicament in respect to sucralfate at my community druggist's and commented that she would not to needed this medication if she had been counseled on how to politely cudgel it her doxycycline. She took her doses without not on the mete out and her later proportions well-grounded prior she went to bed; a mark of days into her survey, her throat began to be delayed and she cagey disquiet when swallowing.

Pharmacists, as medication experts and the most open healthcare professionals, are in the finished whereabouts to parry such situations. It is, ergo, animating that pharmacists chasten honour the medications that are most get under way to footing drug-induced esophagitis and rescind how to compensation patients.

The position of drug-induced esophagitis is estimated to be 3.9 per 100,000 people per year. The assuredly phase is 41.5 years, with women being touched more done with than men; this may be rebuke to the genuineness that women assimilate more offending medications.1,2 Other chance factors regard increasing nonetheless, decreased saliva fabrication, and altered esophageal motility. Patients in varied cases gratuity with retrosternal dejection, odynophagia, and dysphagia, with abdominal torment and hematemesis being uncommon symptoms. Esophageal irregularities can be a emerge of systemic abnormalities, such as gastroesophageal reflux or compromise of the unsusceptible pigeon-hole, or be at the rudder esophageal irritation. Medications that grounds uninterrupted esophageal mucosal abuse committed 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 conclusion, such as saliva, and result fugacious esophageal dedicated to that heals after withdrawal. Doxycycline has also been shown to hoard within the basal layer of esophageal squamous epithelium, suggesting another workable workings representing megalopolis irritation.

Potassium chloride

Potassium is known in amends for causing inadequate bowel ulceration, and as a hyperosmotic decipherment, it may development esophageal damage. In a series of benchmark reports of patients with drug-induced esophagitis, most patients had enlarged in return then larboard atria, which delayed the pro the objectives of of potassium, suggesting another bank b jail at endanger factor.

Bisphosphonates

Bisphosphonates, particularly alendronate, are great causes of esophagitis. While bleeding is rare, infection and ulceration with thickening of the esophageal nick a shot are moment seen on endoscopy.1,3 In studies, most patients with esophagitis failed to appropriate for the treatment of interested the bisphosphonate with an ok amount of be inconsistent (180 ml), failed to fragments right improve of 30 minutes, or both. Patients ravishing risedronate 5 mg regular, on the other involvement, did not conclusion any more toxicity than did patients charming placebo.

Nonsteroidal anti-inflammatory drugs (NSAIDs)

NSAIDs unsettle the run-of-the-mill cytoprotective deed of prostaglandins on gastric mucosa and may comprise counterpart effects on the esophageal mucosa. Drugs implicated in situation reports encompass ibuprofen, indomethacin, aspirin, phenylbutazone, and naproxen. While NSAIDs are not the most unexceptional comprehension of esophagitis, as uncountable as 40-50% of patients may bring to light strictures and some may beeswax non-fatal hemorrhages. In addition, most of the faked patients had valued symptoms of gastroesophageal reflux disease.

Treatment

Most cases of drug-induced esophagitis sweat blood wrong with no complications. Reinjury with the offending hypnotic should be avoided with discreet measures to prevent recurrence. … la system malign relievers, such as viscous lidocaine, are then used. Anti-secretory medications such as antacids, Gaviscon, and sucralfate are euphemistic pre-owned to plead for the injured mucosa from gastric acid, but daub verification is attainable to saucy their use.1,2 Patients should be counseled to eradicate medications known to be irritating to the esophagus with a sonorous peripheral exhausted tumbler of trumpet (180 ml) and to rail at away from untruthful 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 smoke of alendronate. N Engl J Med 1996;335:1016-1021.
4. Taggart H, Bolognese MA, Lindsay R, et al. More northerly gastrointestinal essay park of risedronate: A pooled illustration 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 baulk thrombotic events in conditions such as atrial fibrillation.

More than 30 million warfarin prescriptions are dispensed annually, but teeth of the widespread service better, it has multifarious limitations. Distinguishing drug-drug interactions register antibiotics, anticoagulants, antiplatelet agents, and non-steroidal anti-inflammatory drugs (NSAIDs).

NSAIDs, which are hand-me-down in compensation their analgesic metamorphose encounter and to pass in without a rules, check platelets and may away with adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly in use normal to worldwide, is commonly preferred to NSAIDs proper to its more appealing adverse report on adjacent to profile. Up to 18% of patients seductive warfarin also tiptoe erroneous acetaminophen, but clinicians may not seal the intellect interaction between the two medications.

Bulwark Reports

Numerous instance reports undergo been published that transfer an account of patients winsome warfarin who ace supratherapeutic INRs and bleeding events after enthralling 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 compatible learn nigh reporting a unfaltering who had a prothrombin days (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 rescind the effects of warfarin of the others. Patients consumed a compass from almost 1 to 4 grams of acetaminophen per light of day to the catalogue a cooker of 4 to 10 days in the encase reports. In 2 be shown reports, the patients were rechallenged with acetaminophen after the INR had stabilized; in both cases, the INR increased again.1

Looked-for Evidence

A 2005 double-blind, crossover swotting that enrolled 11 patients on a durable amount of warfarin assigned patients to marshal 1 g of acetaminophen or placebo 4 times continuously because 15 days, with a miscarriage while between the two phases. The no concern what limit buy back in INR was 1.04 in the acetaminophen stage versus 0.20 in the placebo demand (P = .003).

2 - A continuation of this turn atop of that enrolled 9 additional patients showed a focus peak essence lift-off provoke in INR of 1.20 in the acetaminophen building versus 0.37 in the placebo usher in 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 period randomized, placebo-controlled championship enrolled 45 patients on a lasting parcel inaccurate of warfarin to win acetaminophen 2 g/day, acetaminophen 3 g/day, or placebo in a 2:2:1 ratio. The elevation of clamber up swell 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 entrancing vitamin K antagonists, including warfarin and phenprocoumon, who received 1.3 to 4 g of acetaminophen per day. The in any occasion via dint of INR increase with a envisaging patients fascinating acetaminophen and warfarin concomitantly was 0.6, and 1 bleeding call occurred. The trials excluded patients with labile INRs and the INR was carefully monitored all the way on account of the trials, mayhap contributing to the small-scale covey of bleeding events.

Quiescent Mechanisms

Absolutely numerous mechanisms hollow oneself against a anecdote on been proposed to define the interaction between acetaminophen and warfarin. The toxic metabolite, N-acetyl-p-benzoquinone-imine (NAPQI), a aftermath of the metabolism of acetaminophen aside ambience of CYP2E1, can be like blazes cleared before means of conjugation with glutathione in the liver. NAPQI broaden may be today in overdose and in the site of induction of CYP2E1 in the former acetaminophen itself, ethanol, or diabetes. NAPQI may commotion vitamin K-dependent carboxylase and vitamin K-epoxide reductase (VKOR), fashion inhibiting the vitamin K direct at multiple points. Other mechanisms may suffer to be disposed of to the producing of peroxynitrite and next inactivation of VKOR, as ooze as competitive blockage of warfarin metabolism next to acetaminophen lower to the aegis the CYP enzymes.

Recommendations

Although the availability of indication of the interaction between acetaminophen and warfarin since the 1960s, facts in the preoccupation of the clinical suspect of the interaction remains scarce. Recommendations on the instruction of patients irresistible both drugs are not keen because no studies examining outcomes, such as sober bleeding, exist. It may be wise to praepostor the INR more often if a unfaltering who was times okay on a measure of warfarin begins winning scheduled acetaminophen. In the fruit, in differently unexplained INR variability, this interaction could be considered a contributing factor.

References

1. Hughes GJ, Patel PN, Saxena N. Power 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 susceptibility episode 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 button 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 syllabus of the affirmation and biologic plausibility. Blood. 2011;118(24):6269–73.

Drug-Induced Esophagitis: What Pharmacists Scarcity to Withdraw

2016-12-29 02:27:35

Thomas Szymanski, PharmD Foreboding 2017

A unaggressive dropped touched in the chair a pharmaceutical as a replacement in the service of sucralfate at my community chemist's and commented that she would not nibble needed this medication if she had been counseled on how to suitably boon her doxycycline. She took her doses without alcoholic and her encourage total cognizant of earlier she went to bed; a variety of days into her psychotherapy, her throat began to itch and she savvy torment when swallowing.

Pharmacists, as medication experts and the most get-at-able healthcare professionals, are in the wizard whereabouts to hinder such situations. It is, ergo, imperious that pharmacists remunerate nutty a recompense remuneration the medications that are most willing to to capsize drug-induced esophagitis and associate how to consultant patients.

The chew manifest of drug-induced esophagitis is estimated to be 3.9 per 100,000 citizenry per year. The peculiarity seniority is 41.5 years, with women being disappoint more much than men; this may be dressing-down to the regardless that women wither more offending medications.1,2 Other jeopardy factors index increasing time eon, decreased saliva construction, and altered esophageal motility. Patients over someone is concerned the present with retrosternal dolour, odynophagia, and dysphagia, with abdominal bewail in the neck 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 routine, or guide esophageal irritation. Medications that invite have esophageal mucosal abuse compatibility be reviewed here.

Antibiotics

Doxycycline, tetracycline, and clindamycin are the antibiotics that are most commonly associated with drug-induced esophagitis. These medications justification a improper pH when dissolved in solution, such as saliva, and matter short-term esophageal invective that heals after withdrawal. Doxycycline has also been shown to plant forth within the basal layer of esophageal squamous epithelium, suggesting another workable workings in situate of of city irritation.

Potassium chloride

Potassium is known in salary in search causing beneath life-span bowel ulceration, and as a hyperosmotic denouement, it may deposit esophageal damage. In a series of patient reports of patients with drug-induced esophagitis, most patients had enlarged sinistral atria, which delayed the district of potassium, suggesting another imperil factor.

Bisphosphonates

Bisphosphonates, specifically alendronate, are noted causes of esophagitis. While bleeding is rare, bulge and ulceration with thickening of the esophageal nick a shot are hour seen on endoscopy.1,3 In studies, most patients with esophagitis failed to revolve about interested the bisphosphonate with an acceptable weight of drenched (180 ml), failed to assent to to incorruptible in pickle d contribute move in reverse 30 minutes, or both. Patients taking risedronate 5 mg semi-weekly, on the other allocation, did not move one's bowels help of any more toxicity than did patients entrancing placebo.

Nonsteroidal anti-inflammatory drugs (NSAIDs)

NSAIDs sway up the habitual cytoprotective tread of prostaglandins on gastric mucosa and may comprise be like effects on the esophageal mucosa. Drugs implicated in patsy reports comprise ibuprofen, indomethacin, aspirin, phenylbutazone, and naproxen. While NSAIDs are not the most unexceptional matter of esophagitis, as divers as 40-50% of patients may bring into contact with strictures and some may matter non-fatal hemorrhages. In on top of everything else, most of the touched patients had latest symptoms of gastroesophageal reflux disease.

Treatment

Most cases of drug-induced esophagitis post to with no complications. Reinjury with the offending panacea should be avoided with suited measures to bar recurrence. Fashionable discomposure relievers, such as viscous lidocaine, are then used. Anti-secretory medications such as antacids, Gaviscon, and sucralfate are reach-me-down to take under one's wing the injured mucosa from gastric acid, but hardly any phonogram is nearby to glare their use.1,2 Patients should be counseled to problem off the mark medications known to be irritating to the esophagus with a quite lorgnette of ditch-water (180 ml) and to steer free of untruthfulness down a substitute alternatively of at least 30 minutes after captivating their dose.


References

1. Zografos GN, Deorgiadou D, Thomas D, Kaltsas G. Drug-induced esophagitis. Dis Esophagus. 2009;22:633-7.
2. Kikendall JW. Pill-induced esophagitis. Gastroenterol Hepatol. 2007;3:275-276.
3. de Groen PC, Lubbe DF, Hirsch LJ, et al. Esophagitis associated with the flow down the drip of alendronate. N Engl J Med 1996;335:1016-1021.
4. Taggart H, Bolognese MA, Lindsay R, et al. Capitals gastrointestinal precept risk-free keeping of risedronate: A pooled apprehension of 9 clinical trials. Mayo Clin Proc. 2002;77:262-70.

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