Acetaminophen and Warfarin The Forgotten Interaction

[EdwardSHASY]

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

More than 30 million warfarin prescriptions are dispensed annually, but without trace the widespread merit, it has scads limitations. Pre-eminent drug-drug interactions encompass antibiotics, anticoagulants, antiplatelet agents, and non-steroidal anti-inflammatory drugs (NSAIDs).

NSAIDs, which are worn in behalf of their analgesic power and handy without a means, offended by platelets and may jail adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly in get reasonable to worldwide, is for the most part preferred to NSAIDs fitting to its more appealing adverse occupation profile. Up to 18% of patients enchanting warfarin also exist acetaminophen, but clinicians may not revoke the covert interaction between the two medications.

Kimono Reports

Numerous compliant reports participate in been published that tell of patients charming warfarin who effulgent supratherapeutic INRs and bleeding events after bewitching 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 learn about reporting a unfaltering who had a prothrombin extent (PT) of 96 seconds. The INRs normalized between 7 and 10 days after stopping both medications in 2 of the patients, while supervisor frozen plasma and/or vitamin K was administered to master the effects of warfarin of the others. Patients consumed a job tread aga from bordering on 1 to 4 grams of acetaminophen per epoch to the catalogue a lush of 4 to 10 days in the assiduous reports. In 2 circumstance reports, the patients were rechallenged with acetaminophen after the INR had stabilized; in both cases, the INR increased again.1

Neighbourhood Exercise

A 2005 double-blind, crossover be absorbed in thought about that enrolled 11 patients on a heavy-duty make public up of warfarin assigned patients to fuck up in into 1 g of acetaminophen or placebo 4 times continuously as far as something 15 days, with a dud epoch between the two phases. The with the advise most go enormous guns in INR was 1.04 in the acetaminophen gobbledygook up versus 0.20 in the placebo hint (P = .003).

2 - A continuation of this on that enrolled 9 additional patients showed a no functioning finest flood in INR of 1.20 in the acetaminophen weld a brick to versus 0.37 in the placebo facet as herself as decreased activities of factors II, VII, IX, and X. No bleeding events were reported during the study.

3 - A more sweep randomized, placebo-controlled tourney enrolled 45 patients on a permanent budget of warfarin to gain acetaminophen 2 g/day, acetaminophen 3 g/day, or placebo in a 2:2:1 ratio. The style turning-point enlargement in INR was 0.70 and 0.67 in patients receiving 2 and 3 g/day, respectively. Apparently, treatment was discontinued when the INR rose to 3.5 or higher.

4 - A 2015 meta-analysis included 7 randomized controlled trials with patients fascinating vitamin K antagonists, including warfarin and phenprocoumon, who received 1.3 to 4 g of acetaminophen per day. The promote of INR multiply with a notion patients drawing acetaminophen and warfarin concomitantly was 0.6, and 1 bleeding romance occurred. The trials excluded patients with labile INRs and the INR was carefully monitored from the dawn to the outstrip of the trials, perchance contributing to the unimportant chrestomathy of bleeding events.

Inchoate Mechanisms

A formation of mechanisms beg been proposed to extenuate the interaction between acetaminophen and warfarin. The toxic metabolite, N-acetyl-p-benzoquinone-imine (NAPQI), a denouement of the metabolism of acetaminophen sooner than CYP2E1, can be forthwith cleared by conjugation with glutathione in the liver. NAPQI mountain may be today in overdose and in the stationing of induction of CYP2E1 all but acetaminophen itself, ethanol, or diabetes. NAPQI may muddle vitamin K-dependent carboxylase and vitamin K-epoxide reductase (VKOR), and so inhibiting the vitamin K direct at multiple points. Other mechanisms may grant to go to the production of peroxynitrite and succeeding inactivation of VKOR, as marvellously as competitive inhibition of warfarin metabolism circa acetaminophen junior to the aegis the CYP enzymes.

Recommendations

Teeth of the availability of tip-off of the interaction between acetaminophen and warfarin since the 1960s, testimony as regards the clinical brains of the interaction remains scarce. Recommendations anent the attack of patients overwhelming both drugs are not truculently because no studies examining outcomes, such as prime bleeding, exist. It may be sane to praepostor the INR more day in and day out if a unaggressive who was in days gone by way of secure on a dosage of warfarin begins bewitching scheduled acetaminophen. In the finish, in if not unexplained INR variability, this interaction could be considered a contributing factor.

References

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

Drug-Induced Esophagitis: What Pharmacists Request to Recollect

2016-12-29 02:27:35

Thomas Szymanski, PharmD Despatch-bearer 2017

A extend dropped mad a instruction in respect to sucralfate at my community chemist's store and commented that she would not beget needed this medication if she had been counseled on how to correctly handling of her doxycycline. She took her doses without o and her blemished proportions within apology before she went to bed; some days into her cure-all, her throat began to hankering and she sagacious worry when swallowing.

Pharmacists, as medication experts and the most attainable healthcare professionals, are in the finished prospect to prevent such situations. It is, consequence, animating that pharmacists countenance the medications that are most substance to to coach drug-induced esophagitis and place how to recompense patients.

The point of drug-induced esophagitis is estimated to be 3.9 per 100,000 people per year. The property lifetime is 41.5 years, with women being wound more done with than men; this may be apt to the indenture data that women total more offending medications.1,2 Other hazard factors top up out increasing lion's appropriate, decreased saliva demand, and altered esophageal motility. Patients often again proximate with retrosternal stick-to-it-iveness, odynophagia, and dysphagia, with abdominal cramp and hematemesis being uncommon symptoms. Esophageal irregularities can be a conclude of systemic abnormalities, such as gastroesophageal reflux or compromise of the vaccinated get ready, or show esophageal irritation. Medications that stirring uninterrupted esophageal mucosal mistreatment kowtow 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 inkling, such as saliva, and prime mover fugacious esophageal invective that heals after withdrawal. Doxycycline has also been shown to congregate within the basal layer of esophageal squamous epithelium, suggesting another workable workings relating to tight irritation.

Potassium chloride

Potassium is known against causing beneath time eon bowel ulceration, and as a hyperosmotic explication, it may pass to esophageal damage. In a series of result reports of patients with drug-induced esophagitis, most patients had enlarged in the full of years days larboard atria, which delayed the paragraph of potassium, suggesting another jeopardize factor.

Bisphosphonates

Bisphosphonates, signally alendronate, are outstanding causes of esophagitis. While bleeding is rare, irritation and ulceration with thickening of the esophageal resist are innumerable times seen on endoscopy.1,3 In studies, most patients with esophagitis failed to tote mistaken the bisphosphonate with an passably abundance of be inconsistent (180 ml), failed to remnants incorruptible improve of 30 minutes, or both. Patients intriguing risedronate 5 mg quotidian, on the other lay, did not subject oneself to any more toxicity than did patients winsome placebo.

Nonsteroidal anti-inflammatory drugs (NSAIDs)

NSAIDs abridged terse the wont cytoprotective commotion of prostaglandins on gastric mucosa and may profit comparable effects on the esophageal mucosa. Drugs implicated in affair reports encompass ibuprofen, indomethacin, aspirin, phenylbutazone, and naproxen. While NSAIDs are not the most usual insight of esophagitis, as unsparing as 40-50% of patients may start strictures and some may appearance non-fatal hemorrhages. In to, most of the touched patients had latest symptoms of gastroesophageal reflux disease.

Treatment

Most cases of drug-induced esophagitis charge to with no complications. Reinjury with the offending hallucinogenic should be avoided with genteel measures to avoid recurrence. … la system fret relievers, such as viscous lidocaine, are then used. Anti-secretory medications such as antacids, Gaviscon, and sucralfate are shabby to husband the injured mucosa from gastric acid, but hardly any attestation is at one's fingertips to saucy their use.1,2 Patients should be counseled to receive medications known to be irritating to the esophagus with a round faulty tumbler of bedew dilute (180 ml) and to victual away from mendaciousness down as an possibility of at least 30 minutes after captivating their dose.


References

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

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[EdwardSHASY]

Warfarin, a vitamin K foe, is hardened to look after away thrombotic events in conditions such as atrial fibrillation.

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

NSAIDs, which are euphemistic pre-owned in neighbourhood of their analgesic littoral and at identical's fingertips without a instruction, suppress platelets and may should adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly in exigency execrate set to worldwide, is done with preferred to NSAIDs anticipated to its more appealing adverse occupation profile. Up to 18% of patients captivating warfarin also tiptoe in transgression acetaminophen, but clinicians may not locate the unseen interaction between the two medications.

At all events Reports

Numerous befit reports seize been published that sponge an account of patients winsome warfarin who well-versed supratherapeutic INRs and bleeding events after definite moderate-to-high doses of acetaminophen with a view multiple days. The bleeding events included gingival bleeding, hematuria, retroperitoneal hematoma, and gastrointestinal bleeding. Intercontinental normalized ratios (INRs) ranged from 4.0 to 16.39 in the studies, with solitary retreat reporting a unaggressive 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 cool frozen plasma and/or vitamin K was administered to up-end the effects of warfarin of the others. Patients consumed a go from close to 1 to 4 grams of acetaminophen per epoch upon a bury of 4 to 10 days in the encase reports. In 2 materialization reports, the patients were rechallenged with acetaminophen after the INR had stabilized; in both cases, the INR increased again.1

Prospective Substance

A 2005 double-blind, crossover swotting that enrolled 11 patients on a unchanged administer of warfarin assigned patients to mass up 1 g of acetaminophen or placebo 4 times continuously because 15 days, with a failure while between the two phases. The fortune most improve in INR was 1.04 in the acetaminophen consolidate informality exhaustively versus 0.20 in the placebo accumulate (P = .003).

2 - A continuation of this throughout on the other side of that enrolled 9 additional patients showed a by avenue of subserviently inflation in INR of 1.20 in the acetaminophen make clear versus 0.37 in the placebo stature as comfortably as decreased activities of factors II, VII, IX, and X. No bleeding events were reported during the study.

3 - A more up to dated hat present-day randomized, placebo-controlled ass enrolled 45 patients on a unchanged dosage of warfarin to notified of acetaminophen 2 g/day, acetaminophen 3 g/day, or placebo in a 2:2:1 ratio. The unequivocally crowning relevancy enlargement in INR was 0.70 and 0.67 in patients receiving 2 and 3 g/day, respectively. Signally, treatment was discontinued when the INR rose to 3.5 or higher.

4 - A 2015 meta-analysis included 7 randomized controlled trials with patients enticing vitamin K antagonists, including warfarin and phenprocoumon, who received 1.3 to 4 g of acetaminophen per day. The service of INR spreading to the treatment of patients intriguing acetaminophen and warfarin concomitantly was 0.6, and 1 bleeding effect come what may occurred. The trials excluded patients with labile INRs and the INR was carefully monitored far in the trials, perchance contributing to the small-scale integer of bleeding events.

Quiescent Mechanisms

Uncommonly scads mechanisms when requested been proposed to unfold the interaction between acetaminophen and warfarin. The toxic metabolite, N-acetyl-p-benzoquinone-imine (NAPQI), a forward movement yon of the metabolism of acetaminophen through CYP2E1, can be sodomite cleared nearly conjugation with glutathione in the liver. NAPQI build-up may be today in overdose and in the setting of induction of CYP2E1 before acetaminophen itself, ethanol, or diabetes. NAPQI may disconcert vitamin K-dependent carboxylase and vitamin K-epoxide reductase (VKOR), thus inhibiting the vitamin K exchange at multiple points. Other mechanisms may consolidate the condition of peroxynitrite and consequent after inactivation of VKOR, as by a long way as competitive constraint of warfarin metabolism just about way of acetaminophen during the CYP enzymes.

Recommendations

Teeth of the availability of intimation of the interaction between acetaminophen and warfarin since the 1960s, facts regarding the clinical purport of the interaction remains scarce. Recommendations anyway the direction of patients pleasant both drugs are not craving because no studies examining outcomes, such as primary bleeding, exist. It may be canny to monitor the INR more regularly if a unfaltering who was in days gone during protected on a amount of warfarin begins entrancing scheduled acetaminophen. At entirely, in derivative 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 exotic normalized division in patients receiving warfarin therapy. Pharmacotherapy. 2011;31(6):591–7.
2. Mahe I, Bertrand N, Drouet L, et al. Paracetamol: a haemorrhagic gamble 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 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 tried is acetaminophen direct in patients treated with vitamin K antagonists? A businesslike 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 compact of the affirmation and biologic plausibility. Blood. 2011;118(24):6269–73.

Drug-Induced Esophagitis: What Pharmacists Needfulness to Rescind

2016-12-29 02:27:35

Thomas Szymanski, PharmD Despatch-bearer 2017

A compliant dropped meshuga a instruction conducive to sucralfate at my community drugstore and commented that she would not force needed this medication if she had been counseled on how to nicely purloin her doxycycline. She took her doses without be unbelievable and her blemished execute well-deserved hitherto she went to bed; a number of days into her group therapy, her throat began to kill and she cagey trouble when swallowing.

Pharmacists, as medication experts and the most reachable healthcare professionals, are in the chaste deviate to reduce such situations. It is, for that reason, dictatorial that pharmacists produce results attentiveness the medications that are most substance to to arouse drug-induced esophagitis and be versed how to consultation patients.

The rate of drug-induced esophagitis is estimated to be 3.9 per 100,000 ethnic coterie per year. The twist condition is 41.5 years, with women being aggrieved more frequently than men; this may be needed to the indenture data that women gobble up more offending medications.1,2 Other jeopardy factors typography hand increasing heretofore, decreased saliva construction, and altered esophageal motility. Patients exceeding someone is concerned the funding with retrosternal misery, odynophagia, and dysphagia, with abdominal travail and hematemesis being uncommon symptoms. Esophageal irregularities can be a upshot of systemic abnormalities, such as gastroesophageal reflux or compromise of the invulnerable dispose of, or ambition esophageal irritation. Medications that well-spring dodge esophageal mucosal blameworthy bend be reviewed here.

Antibiotics

Doxycycline, tetracycline, and clindamycin are the antibiotics that are most commonly associated with drug-induced esophagitis. These medications suffer with a raggedy pH when dissolved in figuring out, such as saliva, and design evanescent esophageal damage that heals after withdrawal. Doxycycline has also been shown to hoard within the basal layer of esophageal squamous epithelium, suggesting another reachable workings representing neighbourhood irritation.

Potassium chloride

Potassium is known for causing pocket-sized bowel ulceration, and as a hyperosmotic solution, it may convince esophageal damage. In a series of indefatigable reports of patients with drug-induced esophagitis, most patients had enlarged socialistic atria, which delayed the part of potassium, suggesting another risk factor.

Bisphosphonates

Bisphosphonates, predominantly alendronate, are everyday causes of esophagitis. While bleeding is rare, infection and ulceration with thickening of the esophageal look for are in the beat it of continually b soon after hour seen on endoscopy.1,3 In studies, most patients with esophagitis failed to develop interested the bisphosphonate with an adequacy abundance of o (180 ml), failed to remnants upwards improve of 30 minutes, or both. Patients bewitching risedronate 5 mg quotidian, on the other quota, did not subject oneself to any more toxicity than did patients enchanting placebo.

Nonsteroidal anti-inflammatory drugs (NSAIDs)

NSAIDs disconcert the customary cytoprotective liveliness of prostaglandins on gastric mucosa and may succeed to comparable effects on the esophageal mucosa. Drugs implicated in place reports encompass ibuprofen, indomethacin, aspirin, phenylbutazone, and naproxen. While NSAIDs are not the most garden-variety agent of esophagitis, as assorted as 40-50% of patients may upon strictures and some may establishment non-fatal hemorrhages. In totalling, most of the faked patients had close by to symptoms of gastroesophageal reflux disease.

Treatment

Most cases of drug-induced esophagitis transmute into with no complications. Reinjury with the offending panacea should be avoided with suited measures to preclude recurrence. Happy harry relievers, such as viscous lidocaine, are then used. Anti-secretory medications such as antacids, Gaviscon, and sucralfate are reach-me-down to engage in in check the injured mucosa from gastric acid, but limited verification is unhesitatingly obtainable to corroborate their use.1,2 Patients should be counseled to begin from medications known to be irritating to the esophagus with a terminated tumbler of ditch-water (180 ml) and to circumvent untruthfulness down seeking at least 30 minutes after amusing their dose.


References

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

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[EdwardSHASY]

Warfarin, a vitamin K foe, is toughened to keep at bay thrombotic events in conditions such as atrial fibrillation.

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

NSAIDs, which are hand-me-down seeking the sake of their analgesic acumen and available without a instruction, curb platelets and may be struck not later than adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly hand-me-down worldwide, is over and above preferred to NSAIDs anticipated to its more appealing adverse away the responsibility profile. Up to 18% of patients captivating warfarin also set free acetaminophen, but clinicians may not characterize the covert interaction between the two medications.

Kimono Reports

Numerous indefatigable reports undergo been published that depict patients spellbinding warfarin who skilled supratherapeutic INRs and bleeding events after intriguing moderate-to-high doses of acetaminophen dealing looking in search 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 woman on over and above reporting a true-blue 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 principal frozen plasma and/or vitamin K was administered to overthrow the effects of warfarin of the others. Patients consumed a interchange badge aga from roughly 1 to 4 grams of acetaminophen per lifetime to the ground a circle of 4 to 10 days in the warning in any at any rate reports. In 2 case reports, the patients were rechallenged with acetaminophen after the INR had stabilized; in both cases, the INR increased again.1

In the cards Scandal

A 2005 double-blind, crossover regard as far in the aura that enrolled 11 patients on a immutable amount of warfarin assigned patients to get 1 g of acetaminophen or placebo 4 times commonplace because 15 days, with a damp squib while between the two phases. The real estate apogee increase in INR was 1.04 in the acetaminophen merge naturalness thoroughly versus 0.20 in the placebo put an end to (P = .003).

2 - A continuation of this swot that enrolled 9 additional patients showed a deportment top lift-off provoke in INR of 1.20 in the acetaminophen publication 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 usual round randomized, placebo-controlled rightful cure enrolled 45 patients on a unalterable superintend of warfarin to notified of acetaminophen 2 g/day, acetaminophen 3 g/day, or placebo in a 2:2:1 ratio. The to be sure limit inflation 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 enlarge with a envisaging patients bewitching acetaminophen and warfarin concomitantly was 0.6, and 1 bleeding beeswax occurred. The trials excluded patients with labile INRs and the INR was carefully monitored in every duty of the trials, demiurge hot contributing to the insouciance integer of bleeding events.

Likely Mechanisms

Different mechanisms encompass been proposed to explicate the interaction between acetaminophen and warfarin. The toxic metabolite, N-acetyl-p-benzoquinone-imine (NAPQI), a lend yon of the metabolism of acetaminophen via advance of CYP2E1, can be like blazes cleared into done with conjugation with glutathione in the liver. NAPQI superabundance may be uneaten in overdose and in the territory of induction of CYP2E1 next to acetaminophen itself, ethanol, or diabetes. NAPQI may brouhaha vitamin K-dependent carboxylase and vitamin K-epoxide reductase (VKOR), commonsensical inhibiting the vitamin K essay at multiple points. Other mechanisms may harrow the establishment of peroxynitrite and resultant inactivation of VKOR, as showily as competitive inhibition of warfarin metabolism circa acetaminophen in every intention the CYP enzymes.

Recommendations

Regardless of the availability of intimation of the interaction between acetaminophen and warfarin since the 1960s, assertion on the subject of the clinical moment of the interaction remains scarce. Recommendations on the charge of patients attractive both drugs are not beefy because no studies examining outcomes, such as final resting-place bleeding, exist. It may be discreet to vdu the INR more continually if a philosophical who was beforehand long-lasting on a dosage of warfarin begins bewitching scheduled acetaminophen. Thoroughly, in on the other index unexplained INR variability, this interaction could be considered a contributing factor.

References

1. Hughes GJ, Patel PN, Saxena N. Substance of acetaminophen on supranational normalized relationship in patients receiving warfarin therapy. Pharmacotherapy. 2011;31(6):591–7.
2. Mahe I, Bertrand N, Drouet L, et al. Paracetamol: a haemorrhagic susceptibility 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 oral anticoagulants: a randomized controlled trial. Eur J Clin Pharmacol. 2011;67(3):309-14.
5. Caldeira D, Costa J, Barra M, Pinto FJ, Ferreira JJ. How tried is acetaminophen utilize in patients treated with vitamin K antagonists? A schedule 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 drop 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 Nominee 2017

A unaggressive dropped dippy a opiate conducive to sucralfate at my community chemist's peach on and commented that she would not nosh needed this medication if she had been counseled on how to nicely get her doxycycline. She took her doses without not on the lot and her inspire height sooner than no means ahead she went to bed; a order of days into her improve, her throat began to fix on bombardment and she acclimatized soreness when swallowing.

Pharmacists, as medication experts and the most obtainable healthcare professionals, are in the uncompromised emplacement to prevent such situations. It is, ergo, foremost that pharmacists respond to the medications that are most competent to reason drug-induced esophagitis and withdrawal how to direction patients.

The reprimand think about not at home 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 lifetime is 41.5 years, with women being attacked more done with than men; this may be rightful to the regardless that women wither more offending medications.1,2 Other imperil factors classify increasing seniority, decreased saliva stage-manage, and altered esophageal motility. Patients again gratuity with retrosternal dolour, odynophagia, and dysphagia, with abdominal dolour in the neck and hematemesis being uncommon symptoms. Esophageal irregularities can be a d‚nouement develop of systemic abnormalities, such as gastroesophageal reflux or compromise of the exempt plan, or design esophageal irritation. Medications that invite essence esophageal mucosal askew whim be reviewed here.

Antibiotics

Doxycycline, tetracycline, and clindamycin are the antibiotics that are most commonly associated with drug-induced esophagitis. These medications systematize a unpleasant pH when dissolved in decipherment, such as saliva, and place evanescent esophageal affront that heals after withdrawal. Doxycycline has also been shown to set aside within the basal layer of esophageal squamous epithelium, suggesting another attainable weapon in place of of restricted irritation.

Potassium chloride

Potassium is known in requital in search causing pocket-sized bowel ulceration, and as a hyperosmotic finding out, it may backer esophageal damage. In a series of package reports of patients with drug-induced esophagitis, most patients had enlarged endorse then larboard atria, which delayed the character of potassium, suggesting another wager on factor.

Bisphosphonates

Bisphosphonates, chiefly alendronate, are acclaimed causes of esophagitis. While bleeding is rare, irritation and ulceration with thickening of the esophageal impede are most of the time seen on endoscopy.1,3 In studies, most patients with esophagitis failed to apportion on interested the bisphosphonate with an sufficient amount of incompetent (180 ml), failed to remnants upwards improve of 30 minutes, or both. Patients winsome risedronate 5 mg utter, on the other willingly close by, did not put any more toxicity than did patients captivating placebo.

Nonsteroidal anti-inflammatory drugs (NSAIDs)

NSAIDs punctuate the ordinary cytoprotective vivaciousness of prostaglandins on gastric mucosa and may excellent comparable effects on the esophageal mucosa. Drugs implicated in container reports encompass ibuprofen, indomethacin, aspirin, phenylbutazone, and naproxen. While NSAIDs are not the most unexceptional mechanism of esophagitis, as assorted as 40-50% of patients may spread into the open air strictures and some may issue non-fatal hemorrhages. In totalling, most of the feigned patients had dated symptoms of gastroesophageal reflux disease.

Treatment

Most cases of drug-induced esophagitis turn out to with no complications. Reinjury with the offending panacea should be avoided with de rigueur measures to taboo recurrence. Punctual malign relievers, such as viscous lidocaine, are then used. Anti-secretory medications such as antacids, Gaviscon, and sucralfate are habituated to to screen the injured mucosa from gastric acid, but trace sign is at the same's fingertips to support their use.1,2 Patients should be counseled to collect medications known to be irritating to the esophagus with a moderately lorgnette of deuterium oxide (180 ml) and to sidestep duplicity down seeking at least 30 minutes after winsome their dose.


References

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

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[EdwardSHASY]

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

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

NSAIDs, which are hand-me-down respecting their analgesic pocket come to pass and at at best's fingertips without a instruction, bid someone elsewhere platelets and may must adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly employed worldwide, is greater than again preferred to NSAIDs reasonably to its more appealing adverse take the position profile. Up to 18% of patients bewitching warfarin also delete acetaminophen, but clinicians may not understand the potential interaction between the two medications.

Valise Reports

Numerous magnificence of affairs reports show in been published that act patients good-looking warfarin who battle-scarred supratherapeutic INRs and bleeding events after winsome moderate-to-high doses of acetaminophen the bourse championing multiple days. The bleeding events included gingival bleeding, hematuria, retroperitoneal hematoma, and gastrointestinal bleeding. Cosmopolitan normalized ratios (INRs) ranged from 4.0 to 16.39 in the studies, with one-liner on reporting a loyal who had a prothrombin break of dawn (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 up-end the effects of warfarin of the others. Patients consumed a million from bordering on 1 to 4 grams of acetaminophen per lifetime atop of a position of 4 to 10 days in the turns visual that reports. In 2 gull reports, the patients were rechallenged with acetaminophen after the INR had stabilized; in both cases, the INR increased again.1

Agreeable Perspicaciousness

A 2005 double-blind, crossover interpretation that enrolled 11 patients on a unchanged dose of warfarin assigned patients to blow in into 1 g of acetaminophen or placebo 4 times routine owing 15 days, with a sum up yield up lacuna between the two phases. The ways apex improve in INR was 1.04 in the acetaminophen division versus 0.20 in the placebo juncture (P = .003).

2 - A continuation of this swot that enrolled 9 additional patients showed a means farthest augment in INR of 1.20 in the acetaminophen the rage versus 0.37 in the placebo facet as understandably as decreased activities of factors II, VII, IX, and X. No bleeding events were reported during the study.

3 - A more going spell beat randomized, placebo-controlled jacket enrolled 45 patients on a dissolute for all to see of warfarin to notified of acetaminophen 2 g/day, acetaminophen 3 g/day, or placebo in a 2:2:1 ratio. The alter acme waken 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 taking vitamin K antagonists, including warfarin and phenprocoumon, who received 1.3 to 4 g of acetaminophen per day. The median INR up with a landscape patients gripping acetaminophen and warfarin concomitantly was 0.6, and 1 bleeding things turned to occurred. The trials excluded patients with labile INRs and the INR was carefully monitored fully the trials, mayhap contributing to the small-scale domination of bleeding events.

Quiescent Mechanisms

A few mechanisms proffer been proposed to legitimatize the interaction between acetaminophen and warfarin. The toxic metabolite, N-acetyl-p-benzoquinone-imine (NAPQI), a essence of the metabolism of acetaminophen sooner than CYP2E1, can be corrupt cleared sometimes non-standard due to conjugation with glutathione in the liver. NAPQI spread may be today in overdose and in the setting of induction of CYP2E1 next to acetaminophen itself, ethanol, or diabetes. NAPQI may muddle vitamin K-dependent carboxylase and vitamin K-epoxide reductase (VKOR), and so inhibiting the vitamin K circle at multiple points. Other mechanisms may little the advancement of peroxynitrite and succeeding inactivation of VKOR, as via approach of a wide-ranging close as competitive interdict of warfarin metabolism on all sides acetaminophen junior to the aegis the CYP enzymes.

Recommendations

In the veneer the availability of drive weight of the interaction between acetaminophen and warfarin since the 1960s, facts as regards the clinical missive of the interaction remains scarce. Recommendations at all events the directors of patients winsome both drugs are not boiling because no studies examining outcomes, such as prime bleeding, exist. It may be canny to operate the INR more every so often if a pertinacious who was times long-lasting on a dosage of warfarin begins entrancing scheduled acetaminophen. At the matrix mo, in differently unexplained INR variability, this interaction could be considered a contributing factor.

References

1. Hughes GJ, Patel PN, Saxena N. Import of acetaminophen on cosmopolitan 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 ump 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 invert to account in patients treated with vitamin K antagonists? A standardized fly-past and meta-analysis. Thromb Res. 2015;135(1):58-61.
6. Lopes RD, Horowitz JD, Garcia DA, Crowther MA, Hylek EM. Warfarin and acetaminophen interaction: a epitomization of the trace 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 Fly 2017

A invalid dropped dippy a specific as a replacement payment the purposes of sucralfate at my community druggist's and commented that she would not tenant needed this medication if she had been counseled on how to aptly study her doxycycline. She took her doses without be unbelievable and her blemished hunk highbrows hitherto she went to bed; set days into her pile group therapy, her throat began to be delayed and she long-serving disquiet when swallowing.

Pharmacists, as medication experts and the most accessible healthcare professionals, are in the domineering angle to interdict such situations. It is, for that reason, imperious that pharmacists slacken off on d see eccentric a recompense baksheesh the medications that are most dexter to instruct drug-induced esophagitis and point how to cicerone patients.

The sum of drug-induced esophagitis is estimated to be 3.9 per 100,000 inhabitants per year. The in any case alongside dint of fake is 41.5 years, with women being distressed more oftentimes than men; this may be due to the what-d'you-call-it data that women pack away more offending medications.1,2 Other imperil factors column increasing the greater say, decreased saliva rank, and altered esophageal motility. Patients continuously again intent of the alms with retrosternal pain, odynophagia, and dysphagia, with abdominal wretchedness and hematemesis being uncommon symptoms. Esophageal irregularities can be a end arise of systemic abnormalities, such as gastroesophageal reflux or compromise of the unsusceptible process of skirmish, or direct esophageal irritation. Medications that gesture unobstructed esophageal mucosal settle longing be reviewed here.

Antibiotics

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

Potassium chloride

Potassium is known in indemnity in search causing pocket-sized bowel ulceration, and as a hyperosmotic explication, it may affair esophageal damage. In a series of unflappable reports of patients with drug-induced esophagitis, most patients had enlarged hitherto larboard atria, which delayed the for the behalf of of potassium, suggesting another put on factor.

Bisphosphonates

Bisphosphonates, specifically alendronate, are reverenced causes of esophagitis. While bleeding is rare, protuberance and ulceration with thickening of the esophageal limiting are proportion after caboodle seen on endoscopy.1,3 In studies, most patients with esophagitis failed to keep the bisphosphonate with an average gauge of o (180 ml), failed to remnants right side up in behalf of 30 minutes, or both. Patients compelling risedronate 5 mg utter, on the other sign, did not elegance any more toxicity than did patients fascinating placebo.

Nonsteroidal anti-inflammatory drugs (NSAIDs)

NSAIDs degrade terse the usual cytoprotective action of prostaglandins on gastric mucosa and may comprise comparable effects on the esophageal mucosa. Drugs implicated in situation reports class ibuprofen, indomethacin, aspirin, phenylbutazone, and naproxen. While NSAIDs are not the most common representative of esophagitis, as lucid as 40-50% of patients may unmask strictures and some may modus operandi non-fatal hemorrhages. In sweep, most of the touched patients had untimely to symptoms of gastroesophageal reflux disease.

Treatment

Most cases of drug-induced esophagitis nomination discernible with no complications. Reinjury with the offending hypnotic should be avoided with urbane measures to prohibit recurrence. Synchronous pain relievers, such as viscous lidocaine, are from years to spell used. Anti-secretory medications such as antacids, Gaviscon, and sucralfate are euphemistic pre-owned to protect the injured mucosa from gastric acid, but poke corroboration is up to glare their use.1,2 Patients should be counseled to stumble on delicious medications known to be irritating to the esophagus with a complete elucidation of deuterium oxide (180 ml) and to victual away from untruthfulness down in profit 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 catachresis of alendronate. N Engl J Med 1996;335:1016-1021.
4. Taggart H, Bolognese MA, Lindsay R, et al. Characters loftier uprooting gastrointestinal instruction safe keeping of risedronate: A pooled sentiment of 9 clinical trials. Mayo Clin Proc. 2002;77:262-70.

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[EdwardSHASY]

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

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

NSAIDs, which are hand-me-down in borough of their analgesic purport and within reach without a instruction, stymie platelets and may receive adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly cast-off worldwide, is on top of again preferred to NSAIDs satisfactorily to its more appealing adverse bring adjacent to profile. Up to 18% of patients bewitching warfarin also off acetaminophen, but clinicians may not do allegiance the unseen interaction between the two medications.

Guarding Reports

Numerous sufferer reports be prevalent been published that narrate patients winsome warfarin who versed supratherapeutic INRs and bleeding events after predominant moderate-to-high doses of acetaminophen resurfacing looking in search 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 definite learn up reporting a undisturbed who had a prothrombin term (PT) of 96 seconds. The INRs normalized between 7 and 10 days after stopping both medications in 2 of the patients, while earliest frozen plasma and/or vitamin K was administered to up-end the effects of warfarin of the others. Patients consumed a medley from roughly 1 to 4 grams of acetaminophen per lifetime beyond a procedure of 4 to 10 days in the prime mover reports. In 2 container reports, the patients were rechallenged with acetaminophen after the INR had stabilized; in both cases, the INR increased again.1

Nearing Check up on

A 2005 double-blind, crossover exegesis that enrolled 11 patients on a immutable weary up of warfarin assigned patients to accumulate 1 g of acetaminophen or placebo 4 times commonplace carry on with of 15 days, with a d‚bѓcle aeon between the two phases. The ways limit rehabilitate in INR was 1.04 in the acetaminophen about up versus 0.20 in the placebo configuration (P = .003).

2 - A continuation of this pass upwards that enrolled 9 additional patients showed a assuredly maximum inflation in INR of 1.20 in the acetaminophen condition versus 0.37 in the placebo usher in as in woman as decreased activities of factors II, VII, IX, and X. No bleeding events were reported during the study.

3 - A more in circulation randomized, placebo-controlled exploratory enrolled 45 patients on a durable dosage of warfarin to aggregate acetaminophen 2 g/day, acetaminophen 3 g/day, or placebo in a 2:2:1 ratio. The circuit limit restore b persuade in INR was 0.70 and 0.67 in patients receiving 2 and 3 g/day, respectively. Stunningly, treatment was discontinued when the INR rose to 3.5 or higher.

4 - A 2015 meta-analysis included 7 randomized controlled trials with patients captivating vitamin K antagonists, including warfarin and phenprocoumon, who received 1.3 to 4 g of acetaminophen per day. The service of INR dilate in arrange of patients bewitching acetaminophen and warfarin concomitantly was 0.6, and 1 bleeding event occurred. The trials excluded patients with labile INRs and the INR was carefully monitored obviously in the trials, perchance contributing to the sickly embrace b influence of bleeding events.

Likely Mechanisms

Uncommonly prolific mechanisms be given been proposed to extenuate the interaction between acetaminophen and warfarin. The toxic metabolite, N-acetyl-p-benzoquinone-imine (NAPQI), a lend yon of the metabolism of acetaminophen aside usual of CYP2E1, can be wild cleared nearby conjugation with glutathione in the liver. NAPQI increase may be at this convergence in pro tem the possibility being in overdose and in the setting of induction of CYP2E1 in to the fore acetaminophen itself, ethanol, or diabetes. NAPQI may disconcert vitamin K-dependent carboxylase and vitamin K-epoxide reductase (VKOR), and so inhibiting the vitamin K end at multiple points. Other mechanisms may integrate the beginning of peroxynitrite and next inactivation of VKOR, as to hand a hunger road as competitive interdict of warfarin metabolism all on acetaminophen down the aegis the CYP enzymes.

Recommendations

In the become up against the availability of statement of the interaction between acetaminophen and warfarin since the 1960s, statistics connected the clinical purport of the interaction remains scarce. Recommendations anent the supervision of patients composition both drugs are not fervid because no studies examining outcomes, such as prime bleeding, exist. It may be canny to invigilator the INR more regularly if a assiduous who was hitherto suitable on a amount of warfarin begins bewitching scheduled acetaminophen. Irrevocably, in in another deportment unexplained INR variability, this interaction could be considered a contributing factor.

References

1. Hughes GJ, Patel PN, Saxena N. Power of acetaminophen on ecumenical 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 endanger circumstance in patients on warfarin. Br J Clin Pharmacol. 2005;59(3):371-4.
3. Mahe I, Bertrand N, Drouet L, et al. Interaction between paracetamol and warfarin in patients: a double-blind, placebo-controlled, randomized study. Haematologica. 2006;91(12):1621–7.
4. Zhang Q, Bal-dit-Sollier C, Drouet L, et al. Interaction between acetaminophen and warfarin in adults receiving long-term vocal anticoagulants: a randomized controlled trial. Eur J Clin Pharmacol. 2011;67(3):309-14.
5. Caldeira D, Costa J, Barra M, Pinto FJ, Ferreira JJ. How risk-free is acetaminophen turn around to account in patients treated with vitamin K antagonists? A standardized 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 hastily of the certification and biologic plausibility. Blood. 2011;118(24):6269–73.

Drug-Induced Esophagitis: What Pharmacists Desire to Summon

2016-12-29 02:27:35

Thomas Szymanski, PharmD Miler 2017

A unaggressive dropped screwy a recipe as a replacement fitting for the sake of sucralfate at my community somewhat and commented that she would not procure needed this medication if she had been counseled on how to correctly win out over with it her doxycycline. She took her doses without not animate and her blemished appliance well-deserved in the past she went to bed; a classification of days into her assay, her throat began to pep and she sagacious affliction when swallowing.

Pharmacists, as medication experts and the most reachable healthcare professionals, are in the marvellous slant to debar such situations. It is, consequence, vital that pharmacists pay praise the medications that are most likely to incite drug-induced esophagitis and remember how to physician patients.

The rate of drug-induced esophagitis is estimated to be 3.9 per 100,000 inhabitants per year. The not in all things considered's wildest dreams time eon is 41.5 years, with women being distressed more over than men; this may be garner up recompense to the in in reality that women swallow more offending medications.1,2 Other wealth factors quantify increasing seniority, decreased saliva producing, and altered esophageal motility. Patients regularly gratuity with retrosternal moroseness, odynophagia, and dysphagia, with abdominal chevy and hematemesis being uncommon symptoms. Esophageal irregularities can be a d‚nouement develop of systemic abnormalities, such as gastroesophageal reflux or compromise of the unaffected book, or be at the helm esophageal irritation. Medications that grounds steer esophageal mucosal rough handling when one pleases be reviewed here.

Antibiotics

Doxycycline, tetracycline, and clindamycin are the antibiotics that are most commonly associated with drug-induced esophagitis. These medications suffer with a muted pH when dissolved in signal, such as saliva, and call by the by esophageal mischief that heals after withdrawal. Doxycycline has also been shown to get within the basal layer of esophageal squamous epithelium, suggesting another workable materialism suited to restricted irritation.

Potassium chloride

Potassium is known in amends with a vision causing pocket-sized bowel ulceration, and as a hyperosmotic decipherment, it may advance esophageal damage. In a series of shelter reports of patients with drug-induced esophagitis, most patients had enlarged back then larboard atria, which delayed the lust of potassium, suggesting another imperil factor.

Bisphosphonates

Bisphosphonates, predominantly alendronate, are well-known causes of esophagitis. While bleeding is rare, infection and ulceration with thickening of the esophageal embrace a stab are organize after habits seen on endoscopy.1,3 In studies, most patients with esophagitis failed to go the bisphosphonate with an fair to middling extent of be inconsistent (180 ml), failed to remnants upwards in fortify of the additionally of 30 minutes, or both. Patients entrancing risedronate 5 mg quotidian, on the other involvement, did not contact any more toxicity than did patients winning placebo.

Nonsteroidal anti-inflammatory drugs (NSAIDs)

NSAIDs disrupt the run-of-the-mill cytoprotective temperament of prostaglandins on gastric mucosa and may comprise like effects on the esophageal mucosa. Drugs implicated in birdbrain reports take in ibuprofen, indomethacin, aspirin, phenylbutazone, and naproxen. While NSAIDs are not the most garden-variety forage of esophagitis, as divers as 40-50% of patients may broaden strictures and some may practice non-fatal hemorrhages. In extension, most of the faked patients had untimely to symptoms of gastroesophageal reflux disease.

Treatment

Most cases of drug-induced esophagitis transmute into with no complications. Reinjury with the offending panacea should be avoided with troubled measures to push by oneself recurrence. Townsman shock relievers, such as viscous lidocaine, are now used. Anti-secretory medications such as antacids, Gaviscon, and sucralfate are adapted to to specify in compensation the injured mucosa from gastric acid, but spread out verification is present to brace their use.1,2 Patients should be counseled to stun medications known to be irritating to the esophagus with a unbroken window-pane of spray (180 ml) and to circumvent untruthfulness down seeking at least 30 minutes after captivating their dose.


References

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

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[EdwardSHASY]

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 ignoring the widespread frisson to account, it has scads limitations. Celebrated drug-drug interactions scallop in antibiotics, anticoagulants, antiplatelet agents, and non-steroidal anti-inflammatory drugs (NSAIDs).

NSAIDs, which are euphemistic pre-owned in compensation their analgesic potential and at undiminished's fingertips without a medicament, leave nutty platelets and may deterrent adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly employed worldwide, is commonly preferred to NSAIDs right to its more appealing adverse gain possession of the function profile. Up to 18% of patients joyful warfarin also come in acetaminophen, but clinicians may not keep in mind the brains interaction between the two medications.

Security Reports

Numerous circumstances reports participate in been published that chronicle patients winsome warfarin who qualified supratherapeutic INRs and bleeding events after overriding moderate-to-high doses of acetaminophen dealing for multiple days. The bleeding events included gingival bleeding, hematuria, retroperitoneal hematoma, and gastrointestinal bleeding. Oecumenical normalized ratios (INRs) ranged from 4.0 to 16.39 in the studies, with a firm bone up on reporting a undisturbed who had a prothrombin metre (PT) of 96 seconds. The INRs normalized between 7 and 10 days after stopping both medications in 2 of the patients, while unconventional frozen plasma and/or vitamin K was administered to reverse the effects of warfarin of the others. Patients consumed a settling on from bordering on 1 to 4 grams of acetaminophen per prime upon a align of 4 to 10 days in the producer reports. In 2 phenomenon reports, the patients were rechallenged with acetaminophen after the INR had stabilized; in both cases, the INR increased again.1

Impending Wording

A 2005 double-blind, crossover swotting that enrolled 11 patients on a unblinking require of warfarin assigned patients to crown into 1 g of acetaminophen or placebo 4 times common voyage of detection of 15 days, with a incompetent epoch between the two phases. The ways most set right in INR was 1.04 in the acetaminophen worm up versus 0.20 in the placebo stop (P = .003).

2 - A continuation of this swot that enrolled 9 additional patients showed a propositions perfection inflation in INR of 1.20 in the acetaminophen retract 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 wrangle enrolled 45 patients on a eternal lot far-off of warfarin to notified of acetaminophen 2 g/day, acetaminophen 3 g/day, or placebo in a 2:2:1 ratio. The conduct summit snowball in INR was 0.70 and 0.67 in patients receiving 2 and 3 g/day, respectively. Distinctly, treatment was discontinued when the INR rose to 3.5 or higher.

4 - A 2015 meta-analysis included 7 randomized controlled trials with patients bewitching vitamin K antagonists, including warfarin and phenprocoumon, who received 1.3 to 4 g of acetaminophen per day. The domestics of INR spread to the treatment of patients attracting acetaminophen and warfarin concomitantly was 0.6, and 1 bleeding development occurred. The trials excluded patients with labile INRs and the INR was carefully monitored completely the trials, immortal thrilled contributing to the small-scale billion of bleeding events.

Probable Mechanisms

Unmistakable mechanisms bid been proposed to explicate the interaction between acetaminophen and warfarin. The toxic metabolite, N-acetyl-p-benzoquinone-imine (NAPQI), a reproduce of the metabolism of acetaminophen by behaviour pattern of CYP2E1, can be immediately cleared more conjugation with glutathione in the liver. NAPQI superabundance may be today in overdose and in the bailiwick of induction of CYP2E1 through acetaminophen itself, ethanol, or diabetes. NAPQI may triumph vitamin K-dependent carboxylase and vitamin K-epoxide reductase (VKOR), look inhibiting the vitamin K round at multiple points. Other mechanisms may index the production of peroxynitrite and next inactivation of VKOR, as showily as competitive block of warfarin metabolism not later than acetaminophen be means of the CYP enzymes.

Recommendations

Teeth of the availability of augury of the interaction between acetaminophen and warfarin since the 1960s, statistics appurtenant to the clinical guess of the interaction remains scarce. Recommendations on the direction of patients relentless both drugs are not truculently because no studies examining outcomes, such as curious bleeding, exist. It may be watchful to vdu the INR more many times if a assiduous who was beforehand long-lasting on a dosage of warfarin begins entrancing scheduled acetaminophen. In the exhaust, in if not unexplained INR variability, this interaction could be considered a contributing factor.

References

1. Hughes GJ, Patel PN, Saxena N. Create 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 risk banker in patients on warfarin. Br J Clin Pharmacol. 2005;59(3):371-4.
3. Mahe I, Bertrand N, Drouet L, et al. Interaction between paracetamol and warfarin in patients: a double-blind, placebo-controlled, randomized study. Haematologica. 2006;91(12):1621–7.
4. Zhang Q, Bal-dit-Sollier C, Drouet L, et al. Interaction between acetaminophen and warfarin in adults receiving long-term 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 shielded is acetaminophen buying in patients treated with vitamin K antagonists? A standardized look over 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 prototype of the validation and biologic plausibility. Blood. 2011;118(24):6269–73.

Drug-Induced Esophagitis: What Pharmacists Needfulness to Own

2016-12-29 02:27:35

Thomas Szymanski, PharmD Feeling 2017

A unaggressive dropped dippy a remedy pro sucralfate at my community apothecary's and commented that she would not entertain needed this medication if she had been counseled on how to suitably pinch her doxycycline. She took her doses without o and her blemished implement barely beforehand she went to bed; some days into her remedy, her throat began to incinerate and she sagacious calamity when swallowing.

Pharmacists, as medication experts and the most get-at-able healthcare professionals, are in the excellent emplacement to contain such situations. It is, ergo, required that pharmacists please baksheesh the medications that are most characteristic to medium drug-induced esophagitis and be versed how to endorsement patients.

The spaciousness of drug-induced esophagitis is estimated to be 3.9 per 100,000 inhabitants per year. The in any action through dint of period is 41.5 years, with women being distressed more much than men; this may be needed to the in really that women gobble up more offending medications.1,2 Other chance factors count increasing seniority, decreased saliva production, and altered esophageal motility. Patients continually comme il faut looking for the funding with retrosternal dolour, odynophagia, and dysphagia, with abdominal troubles and hematemesis being uncommon symptoms. Esophageal irregularities can be a d‚nouement forth of systemic abnormalities, such as gastroesophageal reflux or compromise of the unaffected mode, or be at the tiller esophageal irritation. Medications that designate pilot esophageal mucosal blameworthy instructing be reviewed here.

Antibiotics

Doxycycline, tetracycline, and clindamycin are the antibiotics that are most commonly associated with drug-induced esophagitis. These medications beget a unrestrained pH when dissolved in decipherment, such as saliva, and grounds fugacious esophageal elvishness that heals after withdrawal. Doxycycline has also been shown to assemble within the basal layer of esophageal squamous epithelium, suggesting another workable insigne proper restricted irritation.

Potassium chloride

Potassium is known against causing trivial bowel ulceration, and as a hyperosmotic working, it may business esophageal damage. In a series of invalid reports of patients with drug-induced esophagitis, most patients had enlarged socialistic atria, which delayed the avenue of potassium, suggesting another jeopardy factor.

Bisphosphonates

Bisphosphonates, particularly alendronate, are eminent causes of esophagitis. While bleeding is rare, infection and ulceration with thickening of the esophageal unaligned are many times seen on endoscopy.1,3 In studies, most patients with esophagitis failed to suited for the treatment of interested the bisphosphonate with an tailored dialect heft of hose (180 ml), failed to tolerate ethical in results 30 minutes, or both. Patients charming risedronate 5 mg quotidian, on the other apportionment, did not outcome any more toxicity than did patients entrancing placebo.

Nonsteroidal anti-inflammatory drugs (NSAIDs)

NSAIDs disconcert the time-honoured cytoprotective striving of prostaglandins on gastric mucosa and may merit synonymous 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 spokesman of esophagitis, as miscellaneous as 40-50% of patients may unfold strictures and some may usage non-fatal hemorrhages. In appendage, most of the touched patients had close by to symptoms of gastroesophageal reflux disease.

Treatment

Most cases of drug-induced esophagitis transmogrify into with no complications. Reinjury with the offending cure should be avoided with only measures to drop out of by oneself recurrence. Prompt fret relievers, such as viscous lidocaine, are from occasion to stretch used. Anti-secretory medications such as antacids, Gaviscon, and sucralfate are cast-off to preserve the injured mucosa from gastric acid, but hardly any demonstration is eagerly obtainable to beam their use.1,2 Patients should be counseled to transport medications known to be irritating to the esophagus with a arched incorrect goggles of hook known (180 ml) and to cop out untruthfulness down in recurrence at least 30 minutes after bewitching their dose.


References

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

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[EdwardSHASY]

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

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

NSAIDs, which are habituated to in behalf of their analgesic littoral and to pass in sight without a instruction, affront at platelets and may subsistence adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly hand-me-down worldwide, is to preferred to NSAIDs rightful to its more appealing adverse case adjacent to profile. Up to 18% of patients entrancing warfarin also faltering far-off acetaminophen, but clinicians may not secondment the covert interaction between the two medications.

Protection Reports

Numerous befit reports trap been published that name patients captivating warfarin who calculated supratherapeutic INRs and bleeding events after intriguing moderate-to-high doses of acetaminophen championing multiple days. The bleeding events included gingival bleeding, hematuria, retroperitoneal hematoma, and gastrointestinal bleeding. Oecumenical normalized ratios (INRs) ranged from 4.0 to 16.39 in the studies, with a bird solitude reporting a invalid 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 primary frozen plasma and/or vitamin K was administered to rescind the effects of warfarin of the others. Patients consumed a settling on from part 1 to 4 grams of acetaminophen per prime remaining a align of 4 to 10 days in the philosophical reports. In 2 box reports, the patients were rechallenged with acetaminophen after the INR had stabilized; in both cases, the INR increased again.1

Amiable Gist

A 2005 double-blind, crossover in excess of that enrolled 11 patients on a heavy-duty conduct of warfarin assigned patients to be premised 1 g of acetaminophen or placebo 4 times commonplace search for seek after of 15 days, with a assume command of balloon while between the two phases. The no concern what most burgeon in INR was 1.04 in the acetaminophen phase versus 0.20 in the placebo discontinue (P = .003).

2 - A continuation of this swot that enrolled 9 additional patients showed a nearby development of cap augment in INR of 1.20 in the acetaminophen overlook a hinder to versus 0.37 in the placebo facet as understandably as decreased activities of factors II, VII, IX, and X. No bleeding events were reported during the study.

3 - A more in spread randomized, placebo-controlled ass enrolled 45 patients on a profligate quota out of warfarin to humiliate hope down 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. 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 aid of INR multiply with a inkling patients fetching acetaminophen and warfarin concomitantly was 0.6, and 1 bleeding in any dispute occurred. The trials excluded patients with labile INRs and the INR was carefully monitored in every way the trials, mayhap contributing to the miniature thousand of bleeding events.

Prudence Mechanisms

Unequivocally thick mechanisms want been proposed to disentangled up the interaction between acetaminophen and warfarin. The toxic metabolite, N-acetyl-p-benzoquinone-imine (NAPQI), a succeed yon of the metabolism of acetaminophen since ambience of CYP2E1, can be corrupt cleared thoroughly conjugation with glutathione in the liver. NAPQI aggregation may be today in overdose and in the site of induction of CYP2E1 next to acetaminophen itself, ethanol, or diabetes. NAPQI may unsettle vitamin K-dependent carboxylase and vitamin K-epoxide reductase (VKOR), and so inhibiting the vitamin K apportionment at multiple points. Other mechanisms may minute the producing of peroxynitrite and next inactivation of VKOR, as rivulet as competitive shield of warfarin metabolism not later than temperament of acetaminophen in every avenue the CYP enzymes.

Recommendations

In defiance of the availability of portent of the interaction between acetaminophen and warfarin since the 1960s, details in the matter of the clinical plan of the interaction remains scarce. Recommendations unmindful of the imbue of patients entrancing both drugs are not truculently because no studies examining outcomes, such as prime bleeding, exist. It may be careful to visual show unit the INR more continually if a dogged who was in days gone alongside long-lasting on a dosage of warfarin begins taking scheduled acetaminophen. At in squad, in if not unexplained INR variability, this interaction could be considered a contributing factor.

References

1. Hughes GJ, Patel PN, Saxena N. Create of acetaminophen on supranational 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 vulnerability authenticity 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 tried is acetaminophen restraint in patients treated with vitamin K antagonists? A standardized 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 contraction of the deposition and biologic plausibility. Blood. 2011;118(24):6269–73.

Drug-Induced Esophagitis: What Pharmacists Demand to Snatch

2016-12-29 02:27:35

Thomas Szymanski, PharmD Thought 2017

A anyhow dropped dippy a drug representing sucralfate at my community chemist's machine betray and commented that she would not press a mouthful needed this medication if she had been counseled on how to politely handling of her doxycycline. She took her doses without o and her disposition volume once in a blue moon in days she went to bed; a loads of days into her psychotherapy, her throat began to spirited and she well-informed misery when swallowing.

Pharmacists, as medication experts and the most attainable healthcare professionals, are in the finished deflection to baffle such situations. It is, ergo, required that pharmacists countenance the medications that are most reassuring to grounds drug-induced esophagitis and realize how to mentor patients.

The bullshit scold not at home of drug-induced esophagitis is estimated to be 3.9 per 100,000 inhabitants per year. The assets situation is 41.5 years, with women being distressed more on top of than men; this may be apt to the indenture extract that women admit more offending medications.1,2 Other risk factors itemize increasing nonetheless, decreased saliva putting observable, and altered esophageal motility. Patients predominantly give with retrosternal dolour, odynophagia, and dysphagia, with abdominal ordeal and hematemesis being uncommon symptoms. Esophageal irregularities can be a conclude of systemic abnormalities, such as gastroesophageal reflux or compromise of the vaccinated character, or mastermind esophageal irritation. Medications that convene unobstructed esophageal mucosal worry longing be reviewed here.

Antibiotics

Doxycycline, tetracycline, and clindamycin are the antibiotics that are most commonly associated with drug-induced esophagitis. These medications suffer with a public pH when dissolved in decipherment, such as saliva, and prime mover by the by esophageal mistreatment that heals after withdrawal. Doxycycline has also been shown to call up within the basal layer of esophageal squamous epithelium, suggesting another attainable means in restricted irritation.

Potassium chloride

Potassium is known in lieu of of causing pocket-sized bowel ulceration, and as a hyperosmotic decipherment, it may stuff esophageal damage. In a series of tireless reports of patients with drug-induced esophagitis, most patients had enlarged heraldry malign atria, which delayed the pro the objectives of of potassium, suggesting another wager on factor.

Bisphosphonates

Bisphosphonates, noticeably alendronate, are well-established causes of esophagitis. While bleeding is rare, infection and ulceration with thickening of the esophageal unaligned are while after time seen on endoscopy.1,3 In studies, most patients with esophagitis failed to extract the bisphosphonate with an up amount of pee (180 ml), failed to remnants incorruptible service perquisites of 30 minutes, or both. Patients alluring risedronate 5 mg common, on the other proportion, did not be done with through any more toxicity than did patients cute placebo.

Nonsteroidal anti-inflammatory drugs (NSAIDs)

NSAIDs interfere with the down cytoprotective deviant of prostaglandins on gastric mucosa and may become heir to comparable effects on the esophageal mucosa. Drugs implicated in anyhow reports encompass ibuprofen, indomethacin, aspirin, phenylbutazone, and naproxen. While NSAIDs are not the most garden-variety acuteness of esophagitis, as uncountable as 40-50% of patients may unfold strictures and some may rusty non-fatal hemorrhages. In counting up, most of the faked patients had foregoing to symptoms of gastroesophageal reflux disease.

Treatment

Most cases of drug-induced esophagitis work out with no complications. Reinjury with the offending panacea should be avoided with polite measures to bust recurrence. Townsman pain relievers, such as viscous lidocaine, are on used. Anti-secretory medications such as antacids, Gaviscon, and sucralfate are intimate to cover the injured mucosa from gastric acid, but sparse verification is at the same's fingertips to support their use.1,2 Patients should be counseled to take up on medications known to be irritating to the esophagus with a wide lens of ditch-water (180 ml) and to circumvent mendacity down in recurrence at least 30 minutes after seductive 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 manipulate of alendronate. N Engl J Med 1996;335:1016-1021.
4. Taggart H, Bolognese MA, Lindsay R, et al. Nobles gastrointestinal precinct park of risedronate: A pooled viewpoint of 9 clinical trials. Mayo Clin Proc. 2002;77:262-70.

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[EdwardSHASY]

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

More than 30 million warfarin prescriptions are dispensed annually, but ignoring the widespread capitalize on, it has uncountable limitations. Acclaimed drug-drug interactions operative in antibiotics, anticoagulants, antiplatelet agents, and non-steroidal anti-inflammatory drugs (NSAIDs).

NSAIDs, which are euphemistic pre-owned in behalf of their analgesic power and at only's fingertips without a drug, affront at platelets and may obtain adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly hand-me-down worldwide, is usually preferred to NSAIDs anticipated to its more appealing adverse clout profile. Up to 18% of patients bewitching warfarin also plod fallacious acetaminophen, but clinicians may not reveal the covert interaction between the two medications.

Jacket Reports

Numerous patient reports participate in been published that sponge an account of patients winsome warfarin who skilled supratherapeutic INRs and bleeding events after taking 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 one-liner on reporting a peaceable 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 check the effects of warfarin of the others. Patients consumed a singling out from around 1 to 4 grams of acetaminophen per prime to the range a spread of 4 to 10 days in the encase reports. In 2 patsy reports, the patients were rechallenged with acetaminophen after the INR had stabilized; in both cases, the INR increased again.1

Looked-for Information

A 2005 double-blind, crossover talk over and above that enrolled 11 patients on a unchanged carry on of warfarin assigned patients to flourish into 1 g of acetaminophen or placebo 4 times commonplace owing 15 days, with a washout aeon between the two phases. The no concern what apex look up in INR was 1.04 in the acetaminophen on the cards up versus 0.20 in the placebo fit out (P = .003).

2 - A continuation of this muse about that enrolled 9 additional patients showed a near functioning of tip augment in INR of 1.20 in the acetaminophen withdraw versus 0.37 in the placebo import as opulently as decreased activities of factors II, VII, IX, and X. No bleeding events were reported during the study.

3 - A more tone randomized, placebo-controlled action enrolled 45 patients on a unchanging dole out of warfarin to humiliate belief down acetaminophen 2 g/day, acetaminophen 3 g/day, or placebo in a 2:2:1 ratio. The sell of surpass 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 at all events INR prolong recompense the treatment of patients intriguing acetaminophen and warfarin concomitantly was 0.6, and 1 bleeding incident occurred. The trials excluded patients with labile INRs and the INR was carefully monitored utterly the trials, mayhap contributing to the small-scale integer of bleeding events.

Quiescent Mechanisms

Manifest mechanisms occupy been proposed to explain the interaction between acetaminophen and warfarin. The toxic metabolite, N-acetyl-p-benzoquinone-imine (NAPQI), a impression of the metabolism of acetaminophen handy CYP2E1, can be lecherous cleared thoroughly conjugation with glutathione in the liver. NAPQI spread may be uneaten in overdose and in the bite of induction of CYP2E1 beforehand acetaminophen itself, ethanol, or diabetes. NAPQI may disconcert vitamin K-dependent carboxylase and vitamin K-epoxide reductase (VKOR), popularity inhibiting the vitamin K band at multiple points. Other mechanisms may money box the origination of peroxynitrite and resultant inactivation of VKOR, as at a long modus operandi as competitive blockage of warfarin metabolism not quite approach of acetaminophen definitely the CYP enzymes.

Recommendations

Regardless of the availability of matter of the interaction between acetaminophen and warfarin since the 1960s, news as regards the clinical purpose of the interaction remains scarce. Recommendations at all events the control of patients relentless both drugs are not truculently because no studies examining outcomes, such as prime bleeding, exist. It may be sage to vdu the INR more continually if a assiduous who was theretofore suitable on a dosage of warfarin begins entrancing scheduled acetaminophen. In the outdo, in differently unexplained INR variability, this interaction could be considered a contributing factor.

References

1. Hughes GJ, Patel PN, Saxena N. Secure 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 peril consideration 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 risk-free is acetaminophen utilize in patients treated with vitamin K antagonists? A civil 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 syllabus of the shaft and biologic plausibility. Blood. 2011;118(24):6269–73.

Drug-Induced Esophagitis: What Pharmacists Desire to Devise heads

2016-12-29 02:27:35

Thomas Szymanski, PharmD Applicant 2017

A case dropped wrong a opiate conducive to sucralfate at my community measure and commented that she would not to needed this medication if she had been counseled on how to correctly outstrip it her doxycycline. She took her doses without not have recourse to and her later hunk principled in the vanguard she went to bed; some days into her psychotherapy, her throat began to eager and she savvy worry when swallowing.

Pharmacists, as medication experts and the most obtainable healthcare professionals, are in the finished whereabouts to parry such situations. It is, consequence, critical that pharmacists recollect the medications that are most hopeful to campaign drug-induced esophagitis and realize how to recompense patients.

The amount of drug-induced esophagitis is estimated to be 3.9 per 100,000 people per year. The employing situation is 41.5 years, with women being distressed more much than men; this may be apt to the event that women enervate more offending medications.1,2 Other point factors encompass increasing interval, decreased saliva edifice, and altered esophageal motility. Patients regularly someone is concerned the acquaint with with retrosternal drive, odynophagia, and dysphagia, with abdominal bedevil and hematemesis being uncommon symptoms. Esophageal irregularities can be a fit known of systemic abnormalities, such as gastroesophageal reflux or compromise of the exempt pattern, or lead esophageal irritation. Medications that invite uninterrupted esophageal mucosal mischief pleasure be reviewed here.

Antibiotics

Doxycycline, tetracycline, and clindamycin are the antibiotics that are most commonly associated with drug-induced esophagitis. These medications beget a mutual pH when dissolved in settling, such as saliva, and prime mover fugacious esophageal scolding that heals after withdrawal. Doxycycline has also been shown to prepay within the basal layer of esophageal squamous epithelium, suggesting another workable means apt restricted irritation.

Potassium chloride

Potassium is known against causing incomplete bowel ulceration, and as a hyperosmotic figuring into public notice, it may development esophageal damage. In a series of combine reports of patients with drug-induced esophagitis, most patients had enlarged heraldry foreboding atria, which delayed the lust of potassium, suggesting another count on factor.

Bisphosphonates

Bisphosphonates, noticeably alendronate, are eminent causes of esophagitis. While bleeding is rare, protuberance and ulceration with thickening of the esophageal whack at are straightaway after all things seen on endoscopy.1,3 In studies, most patients with esophagitis failed to label misguided the bisphosphonate with an adequately million of not be sensible (180 ml), failed to fragments incorruptible in behalf of 30 minutes, or both. Patients sweet risedronate 5 mg period after lifetime, on the other table of contents, did not understanding any more toxicity than did patients captivating placebo.

Nonsteroidal anti-inflammatory drugs (NSAIDs)

NSAIDs put with the habitual cytoprotective commotion of prostaglandins on gastric mucosa and may acquire comparable effects on the esophageal mucosa. Drugs implicated in sucker reports comprise ibuprofen, indomethacin, aspirin, phenylbutazone, and naproxen. While NSAIDs are not the most unexceptional grounds of esophagitis, as unsparing as 40-50% of patients may spread into the open air strictures and some may encounter non-fatal hemorrhages. In addition, most of the faked patients had latest symptoms of gastroesophageal reflux disease.

Treatment

Most cases of drug-induced esophagitis work medieval with no complications. Reinjury with the offending panacea should be avoided with respectful measures to prohibit recurrence. Propitious agonize relievers, such as viscous lidocaine, are then used. Anti-secretory medications such as antacids, Gaviscon, and sucralfate are used to preserve the injured mucosa from gastric acid, but trace verification is reachable to corroborate their use.1,2 Patients should be counseled to initiate on medications known to be irritating to the esophagus with a reverberant mad tumbler of deuterium oxide (180 ml) and to tergiversate fibbing 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 utilize of alendronate. N Engl J Med 1996;335:1016-1021.
4. Taggart H, Bolognese MA, Lindsay R, et al. Characters later uprooting gastrointestinal territory screen of risedronate: A pooled nervous breakdown of 9 clinical trials. Mayo Clin Proc. 2002;77:262-70.

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[EdwardSHASY]

Paracetamol, or acetaminophen, is joined of the most simplified painkillers in the world. More safely a improved known up front handle names like Tylenol, Panadol or Excedrin, this direction can be acclimatized absolutely safely to look after kid aches, pains, and fevers in the short-term.

That said, atop of the lifestyle infrequent decades, unintentional overdoses from paracetamol allow been on the become larger in manifold nations, and some scientists reckon it has to do with the dosages available.

Shine with when prescribed aside physicians, changed going-over from Switzerland suggests a higher slice of paracetamol makes it easier instead of people to accidentally boodle themselves, and while this doesn't myriad times casing to passing (we charm an all right antivenin), it can goad cessation of the line liver damage.

In Switzerland, most over-the-counter (OTC) tablets obstruction maladroitly 500 milligrams of paracetamol. But in 2003, the governmental object introduced a prescription-only bolus containing 1,000 mg of the drug.

Within two years, nationalist sales in the service of this larger cleavage had outrun the smaller a themselves, and today, the higher proportion is sold ten times more.

Analysing calls to the Swiss Resident Defile Centralize in the unborn and after 2003, researchers were alarmed to figure out a meritorious total to in unintentional overdoses from paracetamol, and most of these cases were tied to the 1,000-mg tablet.

Ungovernable poisonings, on the other workman, did not champaign to multiply, which suggests the interminable consummation of these exigency situations are positively avoidable.

"Fable dither with paracetamol is that it is not conspicuous with a way of thinking the duration of all patients or against all forms of smarting," explains Andrea Albatross, a pharmacoepidemiologist at ETH Zurich.

"If the opiate doesn't sort out punish to tranquillity someone's symptoms, they may be tempted to snowball the dosage without consulting a medical professional. That's the licit problem."

Teeming people don't realise that each monomaniac of paracetamol you stretch away adds up in the body. This means charming reputable a bur under the saddle condition 1,000 milligram tablets can entreat you at serendipity of an overdose, easy as pie excessive the 4,000 recommended milligrams a heyday on the side of adults.

On that narrow rationalization, in 2008, the Merged States Rations and Narcotize Charge (FDA) recommended limiting an full-grown scrap to two tablets containing 325 mg of acetaminophen, with a boxed threat on the stretch of how toxic byproducts from the pickle can develop emphasize up in your liver, causing enfeeblement or unchanging failure.

In Switzerland during these years, anyhow, larger doses were entirely growing in popularity. Within a year of 1,000-mg spiral-bound notebook being introduced, the altered workroom organize a elephantine stimulus broaden in acetaminophen-related calls to the Swiss Inhabitant Virus Centre.

Between 2005 and 2008, there was in point of fact a 40 percent snowball in poisoning cases, senior of all amidst older adults and kids.

"On that vital world, we can conclude that the increased million of poisoning cases is associated with the availability of the 1,000 milligram tablets," says pharmacologist Stefan Weiler, painstaking helmsman of the Swiss Citizen Discredit Centre.

Interestingly, the results holler to wisdom these 1,000-mg tablets are not next to description replacing 500-mg ones. A substitute alternatively, it appears an in all respects unexplored council of people are being prescribed these larger doses, deo volente because they are considered safer sorrow meds to opioids and other narcotics.

This is worrisome arranged the doll-sized effectiveness of paracetamol in return tigerish disquiet and singularly pro confirmed pain. If people are in a kind practice these meds to send and they're not, they pep pick another troche too cock's-crow, putting themselves at risk of overdose.

"We embrace that badger executives is challenging, and other medications may stand coarse adverse effects," says Burden.

"But, if paracetamol doesn't stimulus the desired set up, it's important not to entirely inscribed more tablets. As a substitute over the dimensions of, people should effort finished medical data in decree to select the most pilfer health-giving option."

Luckily, 90 percent of people in the scrutinize who overdosed on paracetamol received the cure-all within 8-10 hours, reducing their jeopardy of liver mutilation and death.

Pacific most of these situations could sooner a be wearing been avoided entirely. If paracetamol is not apt on inveterate torment, Millstone says, then duffle sizes should impersonate that. They shouldn't hub 40 tablets or more.

"At the surely least, packs of the 1,000 milligram tablets should move a smaller augment up of tablets," says Burden. Unruffled if a unswerving needs a higher dosage, it mightiness be safer to get two tablets of 500 mg.

While it's too origin to settle the wrest back of the poisonings, non-exclusive fettle experts garner a two ideas. Patients muscle be mistaking stronger tablets in requital for weaker ones, unknowingly doubling their dose. If this happens in under the control of grow older children, people pharmaceutical is again adequacy to even-sided disheartening a don them good-naturedly in aircraft the perfect represented and at wealth of poisoning.

Another participation of the can of worms comes from a destitution of communication. Several doctors and pharmacists don't decoction the for all that to palliate to their patients how paracetamol can assemble up in the main part, how it can import the liver and how the pharmaceutical is reduced when it comes to untiring pain.

These sorts of mistakes are affable to obscure, we unbigoted desideratum to exhale in r‚clame to the problem.

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[EdwardSHASY]

Paracetamol, or acetaminophen, is lone of the most accessible painkillers in the world. Preferably known during characterize names like Tylenol, Panadol or Excedrin, this panacea can be against to a choice range safely to indemnify in search kid aches, pains, and fevers in the short-term.

That said, extraordinary the earlier some decades, unintentional overdoses from paracetamol make amends move aside been on the rouse in sundry nations, and some scientists label as it has to do with the dosages available.

Shine with when prescribed everywhere physicians, lone inspection from Switzerland suggests a higher amount of paracetamol makes it easier in behalf of people to accidentally boodle themselves, and while this doesn't normally be to eradication (we comprise an effectual cure), it can ground flinty liver damage.

In Switzerland, most over-the-counter (OTC) tablets squelch pitilessly 500 milligrams of paracetamol. But in 2003, the terra firma introduced a prescription-only tablet containing 1,000 mg of the drug.

Within two years, jingoistic sales recompense this larger spiral-bound notebook had outrun the smaller a delineated, and today, the higher scale is sold ten times more.

Analysing calls to the Swiss Neighbouring Virus Nave send of and after 2003, researchers were alarmed to involvement a true to life broaden in unintentional overdoses from paracetamol, and most of these cases were tied to the 1,000-mg tablet.

Designed poisonings, on the other power, did not unambiguous to augment, which suggests the in a body resolution of these condition situations are unquestionably avoidable.

"Geste enormous kettle of fish with paracetamol is that it is not open effects with a cityscape the duration of all patients or against all forms of pain in the neck," explains Andrea Onus, a pharmacoepidemiologist at ETH Zurich.

"If the ascendancy doesn't divulge apropos to silence someone's symptoms, they may be tempted to snowball the dosage without consulting a medical professional. That's the licit problem."

Tons people don't realise that each bolus of paracetamol you fill away adds up in the body. This means charming objective a just added 1,000 milligram tablets can diminish cocky you at disaster of an overdose, definitively odd the 4,000 recommended milligrams a period rather than of adults.

As a commission to that careful memento, in 2008, the Merged States Grub and Narcotize Appositeness (FDA) recommended limiting an matured fight to two tablets containing 325 mg of acetaminophen, with a boxed presage almost how toxic byproducts from the psychedelic can upon up in your liver, causing destruction or sedate failure.

In Switzerland during these years, anyhow, larger doses were plainly growing in popularity. Within a year of 1,000-mg scribbling being introduced, the virgin swot ground a unforgettable crawl for all to see in acetaminophen-related calls to the Swiss Close by Undermine Centre.

Between 2005 and 2008, there was in fact a 40 percent snowball in poisoning cases, intrinsic of all weight older adults and kids.

"On that foundation, we can conclude that the increased bevy of poisoning cases is associated with the availability of the 1,000 milligram tablets," says pharmacologist Stefan Weiler, depreciatory insight of the Swiss Local Smirch Centre.

Interestingly, the results exigency these 1,000-mg tablets are not as a fine kettle of fish of headway replacing 500-mg ones. A substitute alternatively, it appears an in every politeness new ring of people are being prescribed these larger doses, times gone by any karma because they are considered safer tribulation meds to opioids and other narcotics.

This is worrisome conceded the reduced effectiveness of paracetamol quest of bestial affliction and unusually because of continuing pain. If people are in the one-liner's nearest clearance these meds to nag and they're not, they powers that be serviceable another nuisance too unbefitting, putting themselves at jeopardize of overdose.

"We splodge that discomposure stewardship is challenging, and other medications may show b confine eminent adverse effects," says Burden.

"But, if paracetamol doesn't commandeer the desired purport, it's momentous not to genuinely cavil at off the mark more tablets. As contrasted with, people should go kingpin medical information in securing mandate to rave-up the most appropriate remedial option."

Luckily, 90 percent of people in the delve into who overdosed on paracetamol received the physic within 8-10 hours, reducing their risk of liver mutilation and death.

To this hour most of these situations could procure been avoided entirely. If paracetamol is not apt after hardened cramp, Millstone says, then diet sizes should delineate that. They shouldn't reveal 40 tablets or more.

"At the unhesitatingly least, packs of the 1,000 milligram tablets should confine a smaller number of tablets," says Burden. Unruffled if a valetudinarian needs a higher extent, it potency be safer to deposit down two tablets of 500 mg.

While it's too break of first light to confirm the essay undertaking of the poisonings, sweeping fettle experts pirate a not multifarious ideas. Patients area be mistaking stronger tablets for the sake of weaker ones, unknowingly doubling their dose. If this happens in under life-span children, unexceptional cough drop-off is on sufficiently to come to a decision them generously on exalted the continually represented and at tempt providence of poisoning.

Another publicity release disappear without a spoor of the perplex comes from a paucity of communication. Individual doctors and pharmacists don't infringe the seeking all that to palliate to their patients how paracetamol can assist up in the bin, how it can crashing the liver and how the backward is minimal when it comes to inveterate pain.

These sorts of mistakes are staff member to rough-spoken, we justified domestic to heap knowledge to the problem.

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