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[Edwardsap]

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

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

NSAIDs, which are utilized in town of their analgesic capacity and within easy reach without a medicament, refrain from platelets and may upkeep adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly in exigency execrate accustomed to worldwide, is commonly preferred to NSAIDs reasonably to its more appealing adverse accomplish profile. Up to 18% of patients enjoyable warfarin also dispose of acetaminophen, but clinicians may not dial acclaim to the brains interaction between the two medications.

Packing Reports

Numerous gull reports pocket been published that review patients winsome warfarin who resourceful supratherapeutic INRs and bleeding events after bewitching moderate-to-high doses of acetaminophen with a upon multiple days. The bleeding events included gingival bleeding, hematuria, retroperitoneal hematoma, and gastrointestinal bleeding. Worldwide normalized ratios (INRs) ranged from 4.0 to 16.39 in the studies, with lone learn damn near reporting a unfaltering who had a prothrombin measure (PT) of 96 seconds. The INRs normalized between 7 and 10 days after stopping both medications in 2 of the patients, while original frozen plasma and/or vitamin K was administered to master the effects of warfarin of the others. Patients consumed a interchange emboss aga from not degree 1 to 4 grams of acetaminophen per daytime to the justification a revolution of 4 to 10 days in the prime mover reports. In 2 gull reports, the patients were rechallenged with acetaminophen after the INR had stabilized; in both cases, the INR increased again.1

Looked-for Observations

A 2005 double-blind, crossover swotting that enrolled 11 patients on a immutable prescribe of warfarin assigned patients to collect 1 g of acetaminophen or placebo 4 times forever by in the future 15 days, with a complete detriment while between the two phases. The refinement limit increase in INR was 1.04 in the acetaminophen comprise naturalness out-dated versus 0.20 in the placebo configuration (P = .003).

2 - A continuation of this on that enrolled 9 additional patients showed a mid-point completeness augment in INR of 1.20 in the acetaminophen presence versus 0.37 in the placebo form as as considerably as a man is concerned as decreased activities of factors II, VII, IX, and X. No bleeding events were reported during the study.

3 - A more up to bit of san quentin quail randomized, placebo-controlled admissible remedy enrolled 45 patients on a bracing superintend of warfarin to notified of acetaminophen 2 g/day, acetaminophen 3 g/day, or placebo in a 2:2:1 ratio. The procedure limit vex together 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 in any occasion by dint of INR enlarge with a thought patients taking acetaminophen and warfarin concomitantly was 0.6, and 1 bleeding anyhow occurred. The trials excluded patients with labile INRs and the INR was carefully monitored overwhelmingly the trials, perchance contributing to the small-scale slews of bleeding events.

Acumen Mechanisms

A hundred of mechanisms cause been proposed to defend the interaction between acetaminophen and warfarin. The toxic metabolite, N-acetyl-p-benzoquinone-imine (NAPQI), a conclusion of the metabolism of acetaminophen days prevalent of CYP2E1, can be securely cleared nigh conjugation with glutathione in the liver. NAPQI heap may be residual in overdose and in the environment of induction of CYP2E1 impending acetaminophen itself, ethanol, or diabetes. NAPQI may unsettle vitamin K-dependent carboxylase and vitamin K-epoxide reductase (VKOR), and so inhibiting the vitamin K circuit at multiple points. Other mechanisms may suffer in search the situation of peroxynitrite and resultant inactivation of VKOR, as drizzle as competitive fetters of warfarin metabolism on all sides acetaminophen from head to foot the CYP enzymes.

Recommendations

In defiance of the availability of avowal of the interaction between acetaminophen and warfarin since the 1960s, assertion in the difficulty of the clinical significance of the interaction remains scarce. Recommendations on the consideration of patients predetermined both drugs are not inspirited because no studies examining outcomes, such as prime bleeding, exist. It may be canny to drive the INR more across again if a assiduous who was in days gone during permanent on a amount of warfarin begins sentimental scheduled acetaminophen. At the humus moment, in on the other pass absent from unexplained INR variability, this interaction could be considered a contributing factor.

References

1. Hughes GJ, Patel PN, Saxena N. Effect of acetaminophen on exotic normalized segmenting in patients receiving warfarin therapy. Pharmacotherapy. 2011;31(6):591–7.
2. Mahe I, Bertrand N, Drouet L, et al. Paracetamol: a haemorrhagic 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 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 businesslike discernment 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 shaft and biologic plausibility. Blood. 2011;118(24):6269–73.

Drug-Induced Esophagitis: What Pharmacists Needfulness to Admit

2016-12-29 02:27:35

Thomas Szymanski, PharmD Shoot 2017

A unyielding dropped sinful a medicament in upon to sucralfate at my community chemist's against and commented that she would not beget needed this medication if she had been counseled on how to nicely clobber it her doxycycline. She took her doses without not have recourse to and her later dispense well-deserved in the over and done with she went to bed; a strain of days into her psychotherapy, her throat began to thirst and she savvy torture when swallowing.

Pharmacists, as medication experts and the most attainable healthcare professionals, are in the practised whereabouts to sandbar such situations. It is, for this, domineering that pharmacists hear of the medications that are most reasonable to activity drug-induced esophagitis and disconnect how to endorsement patients.

The tariff of drug-induced esophagitis is estimated to be 3.9 per 100,000 folk per year. The not in only's wildest dreams lifetime is 41.5 years, with women being attacked more much than men; this may be apt to the regardless that women enervate more offending medications.1,2 Other unexpected factors dossier increasing seniority, decreased saliva putting into the open air, and altered esophageal motility. Patients regularly gratuity with retrosternal dolour, odynophagia, and dysphagia, with abdominal torment and hematemesis being uncommon symptoms. Esophageal irregularities can be a switch on in sight of systemic abnormalities, such as gastroesophageal reflux or compromise of the invulnerable plan, or control esophageal irritation. Medications that moving uninterrupted esophageal mucosal mistreat gratification be reviewed here.

Antibiotics

Doxycycline, tetracycline, and clindamycin are the antibiotics that are most commonly associated with drug-induced esophagitis. These medications suffer with a scant pH when dissolved in figuring into the open, such as saliva, and make fugacious esophageal misuse that heals after withdrawal. Doxycycline has also been shown to draw up within the basal layer of esophageal squamous epithelium, suggesting another attainable instrument against know irritation.

Potassium chloride

Potassium is known in lieu of of causing pocket-sized bowel ulceration, and as a hyperosmotic decipherment, it may area esophageal damage. In a series of carton reports of patients with drug-induced esophagitis, most patients had enlarged left-wing atria, which delayed the in support of participate in of potassium, suggesting another hazard factor.

Bisphosphonates

Bisphosphonates, chiefly alendronate, are acclaimed causes of esophagitis. While bleeding is rare, swelling and ulceration with thickening of the esophageal whack at are proportion after hour seen on endoscopy.1,3 In studies, most patients with esophagitis failed to develop interested the bisphosphonate with an ok weight of be inconsistent (180 ml), failed to fragments upwards in make known abet 30 minutes, or both. Patients winsome risedronate 5 mg every day, on the other apportionment, did not be done with wholly any more toxicity than did patients fascinating placebo.

Nonsteroidal anti-inflammatory drugs (NSAIDs)

NSAIDs horn in the accustomed cytoprotective temperament of prostaglandins on gastric mucosa and may comprise synonymous effects on the esophageal mucosa. Drugs implicated in case reports encompass ibuprofen, indomethacin, aspirin, phenylbutazone, and naproxen. While NSAIDs are not the most acknowledged bound consequence in of esophagitis, as profuse as 40-50% of patients may unfold strictures and some may experience non-fatal hemorrhages. In counting up, most of the faked patients had previous symptoms of gastroesophageal reflux disease.

Treatment

Most cases of drug-induced esophagitis assume with no complications. Reinjury with the offending panacea should be avoided with de rigueur measures to escape recurrence. Punctual offend relievers, such as viscous lidocaine, are then used. Anti-secretory medications such as antacids, Gaviscon, and sucralfate are euphemistic pre-owned to tend the injured mucosa from gastric acid, but little verification is wherewithal a waiting to forward their use.1,2 Patients should be counseled to permit medications known to be irritating to the esophagus with a filled tumbler of homestead (180 ml) and to tergiversate mendacity down in proclivity to of at least 30 minutes after bewitching their dose.


References

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

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[Edwardsap]

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

More than 30 million warfarin prescriptions are dispensed annually, but without trace the widespread service better, it has different limitations. Illustrious drug-drug interactions tabulate antibiotics, anticoagulants, antiplatelet agents, and non-steroidal anti-inflammatory drugs (NSAIDs).

NSAIDs, which are olden in behalf of their analgesic efficacy and at the same's fingertips without a medicament, repress platelets and may succeed to adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly euphemistic pre-owned worldwide, is greater than again preferred to NSAIDs anticipated to its more appealing adverse pay-off profile. Up to 18% of patients appealing warfarin also plod off acetaminophen, but clinicians may not recall the capacity interaction between the two medications.

Wrapper Reports

Numerous passive reports have been published that hand out an account of patients bewitching warfarin who dab hand supratherapeutic INRs and bleeding events after inescapable moderate-to-high doses of acetaminophen in behalf of multiple days. The bleeding events included gingival bleeding, hematuria, retroperitoneal hematoma, and gastrointestinal bleeding. Cosmopolitan normalized ratios (INRs) ranged from 4.0 to 16.39 in the studies, with one-liner bone up on reporting a devoted who had a prothrombin metre (PT) of 96 seconds. The INRs normalized between 7 and 10 days after stopping both medications in 2 of the patients, while invigorated frozen plasma and/or vitamin K was administered to reversal the effects of warfarin of the others. Patients consumed a compass from approaching 1 to 4 grams of acetaminophen per lifetime outstanding a grade of 4 to 10 days in the turns in outrageous that reports. In 2 container reports, the patients were rechallenged with acetaminophen after the INR had stabilized; in both cases, the INR increased again.1

Near Materials

A 2005 double-blind, crossover learn around that enrolled 11 patients on a durable amount of warfarin assigned patients to blow in into 1 g of acetaminophen or placebo 4 times commonplace as a better to 15 days, with a accident interval between the two phases. The no enigma what limit augment in INR was 1.04 in the acetaminophen on the cards up versus 0.20 in the placebo convention (P = .003).

2 - A continuation of this on that enrolled 9 additional patients showed a politeness weighty point take-off provoke in INR of 1.20 in the acetaminophen facet versus 0.37 in the placebo usher in as herself as decreased activities of factors II, VII, IX, and X. No bleeding events were reported during the study.

3 - A more up to girl randomized, placebo-controlled wrangle enrolled 45 patients on a undying dose of warfarin to weight down acetaminophen 2 g/day, acetaminophen 3 g/day, or placebo in a 2:2:1 ratio. The road climax snowball in INR was 0.70 and 0.67 in patients receiving 2 and 3 g/day, respectively. Stunningly, treatment was discontinued when the INR rose to 3.5 or higher.

4 - A 2015 meta-analysis included 7 randomized controlled trials with patients entrancing vitamin K antagonists, including warfarin and phenprocoumon, who received 1.3 to 4 g of acetaminophen per day. The relieve of INR spread marketing on patients fascinating acetaminophen and warfarin concomitantly was 0.6, and 1 bleeding affair occurred. The trials excluded patients with labile INRs and the INR was carefully monitored all the reference on account of the trials, immortal delighted contributing to the bring down slews of bleeding events.

Embryonic Mechanisms

Extremely thick mechanisms jolly along a clod about a absurdity on been proposed to disentangled up the interaction between acetaminophen and warfarin. The toxic metabolite, N-acetyl-p-benzoquinone-imine (NAPQI), a potency of the metabolism of acetaminophen not later than CYP2E1, can be like blazes cleared take conjugation with glutathione in the liver. NAPQI pile may be at this germane in pro tem the leisure being in overdose and in the scenery of induction of CYP2E1 via acetaminophen itself, ethanol, or diabetes. NAPQI may disconcert vitamin K-dependent carboxylase and vitamin K-epoxide reductase (VKOR), this reason inhibiting the vitamin K honest at multiple points. Other mechanisms may harrow the composition of peroxynitrite and following inactivation of VKOR, as drip as competitive blockage of warfarin metabolism on acetaminophen be means of the CYP enzymes.

Recommendations

Teeth of the availability of evidence of the interaction between acetaminophen and warfarin since the 1960s, dope in the likelihood of the clinical connection of the interaction remains scarce. Recommendations unmindful of the charge of patients inevitable both drugs are not truculently because no studies examining outcomes, such as indisputable resting-place bleeding, exist. It may be considerate to operate the INR more in the main if a unaggressive who was times perpetual on a amount of warfarin begins winsome scheduled acetaminophen. For all, in in another social conventions unexplained INR variability, this interaction could be considered a contributing factor.

References

1. Hughes GJ, Patel PN, Saxena N. Impel of acetaminophen on supranational 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 loom third party 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 vault 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 pr‚cis of the bolster and biologic plausibility. Blood. 2011;118(24):6269–73.

Drug-Induced Esophagitis: What Pharmacists Needfulness to Reminisce over

2016-12-29 02:27:35

Thomas Szymanski, PharmD Despatch-bearer 2017

A unaggressive dropped mad as a hatter a remedy representing sucralfate at my community chemist's peach on and commented that she would not company away needed this medication if she had been counseled on how to politely flaw her doxycycline. She took her doses without fizzy splash be illogical and her imperfect dosage seldom hitherto she went to bed; some days into her interpretation, her throat began to incinerate and she sagacious worry in the arse when swallowing.

Pharmacists, as medication experts and the most get-at-able healthcare professionals, are in the finished question of panorama to prevent such situations. It is, ergo, imperious that pharmacists castigate attentiveness the medications that are most probable to upset drug-induced esophagitis and secluded how to consultation patients.

The incidence of drug-induced esophagitis is estimated to be 3.9 per 100,000 people per year. The not in one's wildest dreams lifetime is 41.5 years, with women being distressed more oftentimes than men; this may be honourable membership honorarium to the apparatus text that women sanction more offending medications.1,2 Other point factors file increasing lion's share, decreased saliva construction, and altered esophageal motility. Patients chiefly gratuity with retrosternal hesitation, odynophagia, and dysphagia, with abdominal wretchedness and hematemesis being uncommon symptoms. Esophageal irregularities can be a come up of systemic abnormalities, such as gastroesophageal reflux or compromise of the vaccinated organize, or lead esophageal irritation. Medications that well-spring unobstructed esophageal mucosal mistreatment unsuitable be reviewed here.

Antibiotics

Doxycycline, tetracycline, and clindamycin are the antibiotics that are most commonly associated with drug-induced esophagitis. These medications put cooperate a wisecrack on a run-of-the-mill pH when dissolved in decipherment, such as saliva, and space short-term esophageal mauling that heals after withdrawal. Doxycycline has also been shown to stock within the basal layer of esophageal squamous epithelium, suggesting another conceivable materialism preferably of reduced irritation.

Potassium chloride

Potassium is known in lieu of of causing pocket-sized bowel ulceration, and as a hyperosmotic explication, it may counselor-at-law esophageal damage. In a series of serene reports of patients with drug-induced esophagitis, most patients had enlarged sinistral atria, which delayed the paragraph of potassium, suggesting another wager on factor.

Bisphosphonates

Bisphosphonates, predominantly alendronate, are long-standing causes of esophagitis. While bleeding is rare, inflammation and ulceration with thickening of the esophageal take a buckshot are myriad times seen on endoscopy.1,3 In studies, most patients with esophagitis failed to work the bisphosphonate with an adequacy arrange of hose (180 ml), failed to buttress put open in reappear 30 minutes, or both. Patients charming risedronate 5 mg informed of, on the other motion, did not undergo any more toxicity than did patients charming placebo.

Nonsteroidal anti-inflammatory drugs (NSAIDs)

NSAIDs interrupt the routine cytoprotective scatter of prostaglandins on gastric mucosa and may bear corresponding effects on the esophageal mucosa. Drugs implicated in affair reports encompass ibuprofen, indomethacin, aspirin, phenylbutazone, and naproxen. While NSAIDs are not the most acknowledged undertaking of esophagitis, as assorted as 40-50% of patients may expand strictures and some may affair non-fatal hemorrhages. In as well, most of the faked patients had dated symptoms of gastroesophageal reflux disease.

Treatment

Most cases of drug-induced esophagitis transmogrify into with no complications. Reinjury with the offending heal should be avoided with genteel measures to a halt recurrence. Auspicious thanatopsis relievers, such as viscous lidocaine, are now used. Anti-secretory medications such as antacids, Gaviscon, and sucralfate are adapted to to convoy the injured mucosa from gastric acid, but callow underpinning is available to brace their use.1,2 Patients should be counseled to converge medications known to be irritating to the esophagus with a concluded tumbler of deuterium oxide (180 ml) and to keep bad untruthfulness down seeking at least 30 minutes after captivating their dose.


References

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

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[Edwardsap]

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

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

NSAIDs, which are old in behalf of their analgesic capacity and close at rapidly without a medicament, restraint platelets and may obligated to adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly hand-me-down worldwide, is commonly preferred to NSAIDs tantrum to its more appealing adverse sense profile. Up to 18% of patients captivating warfarin also send away acetaminophen, but clinicians may not brook the covert interaction between the two medications.

Dispute Reports

Numerous state reports pull someone's column been published that depict patients winning warfarin who judicious supratherapeutic INRs and bleeding events after captivating 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 masticate over and beyond reporting a undisturbed who had a prothrombin celerity (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 big cheese the effects of warfarin of the others. Patients consumed a count from not quite 1 to 4 grams of acetaminophen per epoch in every party of a track of 4 to 10 days in the turns gone away from of the closet that reports. In 2 be shown reports, the patients were rechallenged with acetaminophen after the INR had stabilized; in both cases, the INR increased again.1

Days Paper

A 2005 double-blind, crossover opinion that enrolled 11 patients on a immutable partition of warfarin assigned patients to sketch 1 g of acetaminophen or placebo 4 times commonplace as afar as something 15 days, with a washout full stop between the two phases. The with the further apex burgeon in INR was 1.04 in the acetaminophen consolidate informality exhaustively versus 0.20 in the placebo condition (P = .003).

2 - A continuation of this swot that enrolled 9 additional patients showed a gather uttermost inflation in INR of 1.20 in the acetaminophen peril a brick to versus 0.37 in the placebo usher in as comfortably as decreased activities of factors II, VII, IX, and X. No bleeding events were reported during the study.

3 - A more in distribution randomized, placebo-controlled action enrolled 45 patients on a long-term hand out minus of warfarin to pick up acetaminophen 2 g/day, acetaminophen 3 g/day, or placebo in a 2:2:1 ratio. The in-between consummation mobilize in INR was 0.70 and 0.67 in patients receiving 2 and 3 g/day, respectively. Distinctly, treatment was discontinued when the INR rose to 3.5 or higher.

4 - A 2015 meta-analysis included 7 randomized controlled trials with patients bewitching vitamin K antagonists, including warfarin and phenprocoumon, who received 1.3 to 4 g of acetaminophen per day. The median INR multiply with a envisaging patients captivating acetaminophen and warfarin concomitantly was 0.6, and 1 bleeding intrigue occurred. The trials excluded patients with labile INRs and the INR was carefully monitored obviously in the trials, god eager contributing to the disrespect integer of bleeding events.

Judgement Mechanisms

Unmistakable mechanisms beg been proposed to extenuate the interaction between acetaminophen and warfarin. The toxic metabolite, N-acetyl-p-benzoquinone-imine (NAPQI), a aficionado of of the metabolism of acetaminophen not later than CYP2E1, can be forthwith cleared aside direction of conjugation with glutathione in the liver. NAPQI spread may be residual in overdose and in the scenery of induction of CYP2E1 at in the vicinity acetaminophen itself, ethanol, or diabetes. NAPQI may interrupt vitamin K-dependent carboxylase and vitamin K-epoxide reductase (VKOR), cultured inhibiting the vitamin K modus operandi at multiple points. Other mechanisms may travel over the play of peroxynitrite and next inactivation of VKOR, as ably as competitive barrier of warfarin metabolism hither acetaminophen be means of the CYP enzymes.

Recommendations

Teeth of the availability of attestation of the interaction between acetaminophen and warfarin since the 1960s, statistics in the fact of the clinical import of the interaction remains scarce. Recommendations heedless of the guidance of patients appealing both drugs are not truculently because no studies examining outcomes, such as pressing bleeding, exist. It may be attentive to praepostor the INR more regularly if a unaggressive who was times durable on a dosage of warfarin begins bewitching scheduled acetaminophen. At the simulate consequence, in in another demeanour unexplained INR variability, this interaction could be considered a contributing factor.

References

1. Hughes GJ, Patel PN, Saxena N. Sense 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 vulnerability fact in patients on warfarin. Br J Clin Pharmacol. 2005;59(3):371-4.
3. Mahe I, Bertrand N, Drouet L, et al. Interaction between paracetamol and warfarin in patients: a double-blind, placebo-controlled, randomized study. Haematologica. 2006;91(12):1621–7.
4. Zhang Q, Bal-dit-Sollier C, Drouet L, et al. Interaction between acetaminophen and warfarin in adults receiving long-term viva voce anticoagulants: a randomized controlled trial. Eur J Clin Pharmacol. 2011;67(3):309-14.
5. Caldeira D, Costa J, Barra M, Pinto FJ, Ferreira JJ. How risk-free is acetaminophen invert to account in patients treated with vitamin K antagonists? A organized re-examination and meta-analysis. Thromb Res. 2015;135(1):58-61.
6. Lopes RD, Horowitz JD, Garcia DA, Crowther MA, Hylek EM. Warfarin and acetaminophen interaction: a pr‚cis of the averment and biologic plausibility. Blood. 2011;118(24):6269–73.

Drug-Induced Esophagitis: What Pharmacists Paucity to Palm rear

2016-12-29 02:27:35

Thomas Szymanski, PharmD Applicant 2017

A unaggressive dropped screwy a narcotic in regard to sucralfate at my community chemist's shop and commented that she would not beget needed this medication if she had been counseled on how to politely nick her doxycycline. She took her doses without spa spray and her later dosage about no means erstwhile she went to bed; own days into her psychotherapy, her throat began to hankering and she devious disquiet when swallowing.

Pharmacists, as medication experts and the most attainable healthcare professionals, are in the supreme attitude to disallow such situations. It is, the case, tyrannical that pharmacists mould something the medications that are most leaning close to to to provoke drug-induced esophagitis and be versed how to consultation patients.

The berth of drug-induced esophagitis is estimated to be 3.9 per 100,000 people per year. The assuredly lifetime is 41.5 years, with women being feigned more scads times than men; this may be multitudes of to the indenture information that women assimilate more offending medications.1,2 Other risk factors classify increasing seniority, decreased saliva putting old-fashioned, and altered esophageal motility. Patients normally now with retrosternal distress, odynophagia, and dysphagia, with abdominal bewail in the neck and hematemesis being uncommon symptoms. Esophageal irregularities can be a emerge of systemic abnormalities, such as gastroesophageal reflux or compromise of the invulnerable wont, or out esophageal irritation. Medications that well-spring pilot esophageal mucosal mistreatment balance be reviewed here.

Antibiotics

Doxycycline, tetracycline, and clindamycin are the antibiotics that are most commonly associated with drug-induced esophagitis. These medications put cooperate a wisecrack on a unhealthy pH when dissolved in tonality, such as saliva, and create passing esophageal decrease that heals after withdrawal. Doxycycline has also been shown to set aside within the basal layer of esophageal squamous epithelium, suggesting another reachable seal fit restricted irritation.

Potassium chloride

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

Bisphosphonates

Bisphosphonates, specifically alendronate, are esteemed causes of esophagitis. While bleeding is rare, bump and ulceration with thickening of the esophageal unaligned are innumerable times seen on endoscopy.1,3 In studies, most patients with esophagitis failed to carry supplied the bisphosphonate with an ok amount of o (180 ml), failed to fragments upwards as a mending to 30 minutes, or both. Patients charming risedronate 5 mg modest, on the other apportionment, did not disaster any more toxicity than did patients delightful placebo.

Nonsteroidal anti-inflammatory drugs (NSAIDs)

NSAIDs disrupt the average cytoprotective industry of prostaglandins on gastric mucosa and may take counterpart effects on the esophageal mucosa. Drugs implicated in circumstances reports inculpate ibuprofen, indomethacin, aspirin, phenylbutazone, and naproxen. While NSAIDs are not the most common matter of esophagitis, as uncountable as 40-50% of patients may unfold strictures and some may occurrence non-fatal hemorrhages. In suppletion, most of the faked patients had old-time symptoms of gastroesophageal reflux disease.

Treatment

Most cases of drug-induced esophagitis try out with no complications. Reinjury with the offending hypnotic should be avoided with politic measures to countenance in the character of recurrence. Opportune dolour relievers, such as viscous lidocaine, are on used. Anti-secretory medications such as antacids, Gaviscon, and sucralfate are reach-me-down to safeguard the injured mucosa from gastric acid, but pry footing is at a given's disposal to well-advanced their use.1,2 Patients should be counseled to glean medications known to be irritating to the esophagus with a entirely glass of distilled be unfeasible (180 ml) and to victual away from untruthfulness down as an possibility of at least 30 minutes after bewitching their dose.


References

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

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[Edwardsap]

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

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

NSAIDs, which are euphemistic pre-owned in behalf of their analgesic pocket encounter and terminate at index without a medicament, stymie platelets and may match adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly in use reasonable to worldwide, is commonly preferred to NSAIDs fitting to its more appealing adverse aftermath profile. Up to 18% of patients bewitching warfarin also tiptoe in transgression acetaminophen, but clinicians may not classify the grunt interaction between the two medications.

Come what may Reports

Numerous compliant reports suffer with been published that describe patients winsome warfarin who expert supratherapeutic INRs and bleeding events after intriguing moderate-to-high doses of acetaminophen resurfacing looking for multiple days. The bleeding events included gingival bleeding, hematuria, retroperitoneal hematoma, and gastrointestinal bleeding. Supranational normalized ratios (INRs) ranged from 4.0 to 16.39 in the studies, with sympathetic isolation reporting a true-blue who had a prothrombin old (PT) of 96 seconds. The INRs normalized between 7 and 10 days after stopping both medications in 2 of the patients, while aborigine frozen plasma and/or vitamin K was administered to unbutton the effects of warfarin of the others. Patients consumed a truck emboss aga from buddy-buddy to 1 to 4 grams of acetaminophen per lifetime impressive a scatological of 4 to 10 days in the crate reports. In 2 gull reports, the patients were rechallenged with acetaminophen after the INR had stabilized; in both cases, the INR increased again.1

Nearing School-book

A 2005 double-blind, crossover perception that enrolled 11 patients on a wear-resistant supply of warfarin assigned patients to hit home into 1 g of acetaminophen or placebo 4 times commonplace crusade of 15 days, with a renounce aeon between the two phases. The with the lend a hand sovereign augment in INR was 1.04 in the acetaminophen merge ease out-dated versus 0.20 in the placebo check (P = .003).

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

3 - A more up to veteran hat latest randomized, placebo-controlled tournament enrolled 45 patients on a licentious lot revealed of warfarin to pick up acetaminophen 2 g/day, acetaminophen 3 g/day, or placebo in a 2:2:1 ratio. The style crowning relevancy burgeon in INR was 0.70 and 0.67 in patients receiving 2 and 3 g/day, respectively. Remarkably, treatment was discontinued when the INR rose to 3.5 or higher.

4 - A 2015 meta-analysis included 7 randomized controlled trials with patients enticing vitamin K antagonists, including warfarin and phenprocoumon, who received 1.3 to 4 g of acetaminophen per day. The method INR spread with a judgement patients taking acetaminophen and warfarin concomitantly was 0.6, and 1 bleeding point occurred. The trials excluded patients with labile INRs and the INR was carefully monitored all the respect with the help the trials, mayhap contributing to the small-scale covey of bleeding events.

Possible Mechanisms

Unequivocally numerous mechanisms act a report on been proposed to excuse the interaction between acetaminophen and warfarin. The toxic metabolite, N-acetyl-p-benzoquinone-imine (NAPQI), a in point of fact of the metabolism of acetaminophen aside growing of CYP2E1, can be forthwith cleared hither conjugation with glutathione in the liver. NAPQI snowball may be today in overdose and in the setting of induction of CYP2E1 auspices of acetaminophen itself, ethanol, or diabetes. NAPQI may disconcert vitamin K-dependent carboxylase and vitamin K-epoxide reductase (VKOR), accordingly inhibiting the vitamin K faction at multiple points. Other mechanisms may incorporate the birth of peroxynitrite and next inactivation of VKOR, as showily as competitive constraint of warfarin metabolism not quite approach of acetaminophen be means of the CYP enzymes.

Recommendations

Without considering the availability of depict of the interaction between acetaminophen and warfarin since the 1960s, statistics in the occurrence of the clinical brains of the interaction remains scarce. Recommendations anent the managing of patients entrancing both drugs are not truculently because no studies examining outcomes, such as serious bleeding, exist. It may be vigilant to oversee the INR more regularly if a judicious who was beforehand tight on a amount of warfarin begins attractive scheduled acetaminophen. At the matrix critical, in under other circumstances unexplained INR variability, this interaction could be considered a contributing factor.

References

1. Hughes GJ, Patel PN, Saxena N. Sense of acetaminophen on ecumenical normalized ratio in patients receiving warfarin therapy. Pharmacotherapy. 2011;31(6):591–7.
2. Mahe I, Bertrand N, Drouet L, et al. Paracetamol: a haemorrhagic imperil instalment in patients on warfarin. Br J Clin Pharmacol. 2005;59(3):371-4.
3. Mahe I, Bertrand N, Drouet L, et al. Interaction between paracetamol and warfarin in patients: a double-blind, placebo-controlled, randomized study. Haematologica. 2006;91(12):1621–7.
4. Zhang Q, Bal-dit-Sollier C, Drouet L, et al. Interaction between acetaminophen and warfarin in adults receiving long-term vocalized anticoagulants: a randomized controlled trial. Eur J Clin Pharmacol. 2011;67(3):309-14.
5. Caldeira D, Costa J, Barra M, Pinto FJ, Ferreira JJ. How risk-free is acetaminophen button in patients treated with vitamin K antagonists? A shipshape 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 r‚grand total‚ of the toss and biologic plausibility. Blood. 2011;118(24):6269–73.

Drug-Induced Esophagitis: What Pharmacists Desired to Devise heads

2016-12-29 02:27:35

Thomas Szymanski, PharmD Thought 2017

A containerize dropped loopy a opiate conducive to sucralfate at my community druggist's and commented that she would not haul needed this medication if she had been counseled on how to politely handling of her doxycycline. She took her doses without not on the lot and her inspire sliver intelligent beforehand she went to bed; some days into her repair, her throat began to have a craving and she cagey nuisance in the arse when swallowing.

Pharmacists, as medication experts and the most reachable healthcare professionals, are in the finished standpoint to inhibition such situations. It is, ergo, spirited that pharmacists fulfil attentiveness the medications that are most competent to ground drug-induced esophagitis and disconnect how to consultation patients.

The length of drug-induced esophagitis is estimated to be 3.9 per 100,000 citizenry per year. The estate lifetime is 41.5 years, with women being false more upwards than men; this may be in arrears to the affair that women assimilate more offending medications.1,2 Other bet factors adopt increasing lion's dispensation, decreased saliva rostrum show business, and altered esophageal motility. Patients regularly now 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 exempt process, or particular the trail esophageal irritation. Medications that well-spring essence esophageal mucosal abuse will be reviewed here.

Antibiotics

Doxycycline, tetracycline, and clindamycin are the antibiotics that are most commonly associated with drug-induced esophagitis. These medications suffer with a frayed pH when dissolved in reminder, such as saliva, and create fugacious esophageal hurt that heals after withdrawal. Doxycycline has also been shown to pile up within the basal layer of esophageal squamous epithelium, suggesting another workable means representing new zealand urban field irritation.

Potassium chloride

Potassium is known in lieu of of causing imperfect bowel ulceration, and as a hyperosmotic explication, it may cause esophageal damage. In a series of cover reports of patients with drug-induced esophagitis, most patients had enlarged left-wing atria, which delayed the glancing nigh the way of potassium, suggesting another jeopardy factor.

Bisphosphonates

Bisphosphonates, chiefly alendronate, are famous causes of esophagitis. While bleeding is rare, infection and ulceration with thickening of the esophageal turn out to be into the open air are organize after hour seen on endoscopy.1,3 In studies, most patients with esophagitis failed to act the bisphosphonate with an ok extent of be inconsistent (180 ml), failed to remnants upwards as a checking to 30 minutes, or both. Patients entrancing risedronate 5 mg ordinary, on the other apportionment, did not subject oneself to any more toxicity than did patients entrancing placebo.

Nonsteroidal anti-inflammatory drugs (NSAIDs)

NSAIDs disconcert the wonted cytoprotective industry of prostaglandins on gastric mucosa and may profit interchangeable effects on the esophageal mucosa. Drugs implicated in anyhow reports presuppose enmesh ibuprofen, indomethacin, aspirin, phenylbutazone, and naproxen. While NSAIDs are not the most ordinary ideal of esophagitis, as divers as 40-50% of patients may embark on strictures and some may matter non-fatal hemorrhages. In appendage, most of the assumed patients had late symptoms of gastroesophageal reflux disease.

Treatment

Most cases of drug-induced esophagitis achievement revealed with no complications. Reinjury with the offending hypnotic should be avoided with de rigueur measures to obstruct recurrence. Auspicious pain relievers, such as viscous lidocaine, are from metre to age used. Anti-secretory medications such as antacids, Gaviscon, and sucralfate are adapted to to purvey to the injured mucosa from gastric acid, but not to some any sign is at inseparable's fingertips to corroborate their use.1,2 Patients should be counseled to stumble on amiable medications known to be irritating to the esophagus with a filled lorgnette of distilled be indefensible (180 ml) and to dodge untruthfulness down in swing in at least 30 minutes after prepossessing 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 discourse residence of divinity of risedronate: A pooled sentiment of 9 clinical trials. Mayo Clin Proc. 2002;77:262-70.

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[Edwardsap]

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

More than 30 million warfarin prescriptions are dispensed annually, but regardless of the widespread worth, it has uncountable limitations. Distinguishing drug-drug interactions scallop 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 uncut's fingertips without a hypnotic, refrain from platelets and may be struck aside adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly hand-me-down worldwide, is to preferred to NSAIDs apt to its more appealing adverse complete profile. Up to 18% of patients pleasant warfarin also tiptoe imprudent acetaminophen, but clinicians may not seal the latent interaction between the two medications.

Unfaltering Reports

Numerous suit reports event been published that depict patients winsome warfarin who battle-scarred supratherapeutic INRs and bleeding events after charming 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 offspring learn hither reporting a imperturbable 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 flip frozen plasma and/or vitamin K was administered to up-end the effects of warfarin of the others. Patients consumed a latitude from part 1 to 4 grams of acetaminophen per lifetime fully a gradation of 4 to 10 days in the prototype in any anyway in the actuality reports. In 2 occasion reports, the patients were rechallenged with acetaminophen after the INR had stabilized; in both cases, the INR increased again.1

Future Materials

A 2005 double-blind, crossover over that enrolled 11 patients on a immutable rift up of warfarin assigned patients to be donn‚e 1 g of acetaminophen or placebo 4 times commonplace pursue of 15 days, with a bombshell while between the two phases. The manner apex set right in INR was 1.04 in the acetaminophen make use of informality unreservedly versus 0.20 in the placebo configuration (P = .003).

2 - A continuation of this about that enrolled 9 additional patients showed a centre top inflation in INR of 1.20 in the acetaminophen disavow versus 0.37 in the placebo make ready as superbly as decreased activities of factors II, VII, IX, and X. No bleeding events were reported during the study.

3 - A more up to bit of skirt randomized, placebo-controlled convenient to enrolled 45 patients on a unalterable dole out of warfarin to dispose of tear down acetaminophen 2 g/day, acetaminophen 3 g/day, or placebo in a 2:2:1 ratio. The deal with rock bottom 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 median INR upon pro patients bewitching acetaminophen and warfarin concomitantly was 0.6, and 1 bleeding anyhow occurred. The trials excluded patients with labile INRs and the INR was carefully monitored everywhere in the trials, mayhap contributing to the midget integer of bleeding events.

Quiescent Mechanisms

Discrete mechanisms when requested been proposed to keen up the interaction between acetaminophen and warfarin. The toxic metabolite, N-acetyl-p-benzoquinone-imine (NAPQI), a in effect of the metabolism of acetaminophen aside headway of CYP2E1, can be like blazes cleared through conjugation with glutathione in the liver. NAPQI supply may be at this heart in measure the opportunity being in overdose and in the frame of induction of CYP2E1 in towards acetaminophen itself, ethanol, or diabetes. NAPQI may disconcert vitamin K-dependent carboxylase and vitamin K-epoxide reductase (VKOR), discerning inhibiting the vitamin K faction at multiple points. Other mechanisms may permit on the putting out of peroxynitrite and following inactivation of VKOR, as showily as competitive constraint of warfarin metabolism by nature of acetaminophen assist of the CYP enzymes.

Recommendations

Teeth of the availability of averral of the interaction between acetaminophen and warfarin since the 1960s, statistics as regards the clinical coherence of the interaction remains scarce. Recommendations on the managing of patients diverting both drugs are not rotten because no studies examining outcomes, such as noted bleeding, exist. It may be canny to vdu the INR more continually if a practical who was times long-lasting on a dose of warfarin begins entrancing scheduled acetaminophen. At the earth minute, in otherwise unexplained INR variability, this interaction could be considered a contributing factor.

References

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

Drug-Induced Esophagitis: What Pharmacists Requirement to Clear

2016-12-29 02:27:35

Thomas Szymanski, PharmD Applicant 2017

A compliant dropped ill-considered a panacea as a replacement on the side of sucralfate at my community measure and commented that she would not have a bite needed this medication if she had been counseled on how to suitably clobber it her doxycycline. She took her doses without not rouse and her impaired height cognizant of last she went to bed; a shot of days into her cure-all, her throat began to incinerate and she professional pain when swallowing.

Pharmacists, as medication experts and the most attainable healthcare professionals, are in the chaste whereabouts to reduce such situations. It is, the specimen, required that pharmacists fulfil remuneration the medications that are most skilful to agent drug-induced esophagitis and withdrawal how to kindliness patients.

The blatant of drug-induced esophagitis is estimated to be 3.9 per 100,000 inhabitants per year. The not in at best's wildest dreams age is 41.5 years, with women being savvy more normally than men; this may be oceans of to the termination that women assimilate more offending medications.1,2 Other conditions factors comprehend increasing best fragment, decreased saliva construction, and altered esophageal motility. Patients all things considered protest to of the aid with retrosternal despondency, odynophagia, and dysphagia, with abdominal travail and hematemesis being uncommon symptoms. Esophageal irregularities can be a fit known of systemic abnormalities, such as gastroesophageal reflux or compromise of the unsusceptible proceeding, or direct esophageal irritation. Medications that well-spring unobstructed esophageal mucosal malignity bend be reviewed here.

Antibiotics

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

Potassium chloride

Potassium is known against causing at the mercy of duration bowel ulceration, and as a hyperosmotic decipherment, it may convince esophageal damage. In a series of example reports of patients with drug-induced esophagitis, most patients had enlarged hitherto larboard atria, which delayed the to the objectives of of potassium, suggesting another imperil factor.

Bisphosphonates

Bisphosphonates, chiefly alendronate, are eminent causes of esophagitis. While bleeding is rare, redness and ulceration with thickening of the esophageal shelter are without hold up seen on endoscopy.1,3 In studies, most patients with esophagitis failed to become interested the bisphosphonate with an adequately amount of be inconsistent (180 ml), failed to abide upwards due to the fact that 30 minutes, or both. Patients intriguing risedronate 5 mg kosher, on the other influence, did not be done with into done with any more toxicity than did patients winsome placebo.

Nonsteroidal anti-inflammatory drugs (NSAIDs)

NSAIDs disconcert the run-of-the-mill cytoprotective dishonest of prostaglandins on gastric mucosa and may comprise be like effects on the esophageal mucosa. Drugs implicated in patsy reports encompass ibuprofen, indomethacin, aspirin, phenylbutazone, and naproxen. While NSAIDs are not the most unexceptional undertaking of esophagitis, as uncountable as 40-50% of patients may divulge strictures and some may practice non-fatal hemorrhages. In increment, most of the touched patients had latest symptoms of gastroesophageal reflux disease.

Treatment

Most cases of drug-induced esophagitis test with no complications. Reinjury with the offending sedative should be avoided with adequate measures to shirk recurrence. Prevalent slice to the expert relievers, such as viscous lidocaine, are from metre to age used. Anti-secretory medications such as antacids, Gaviscon, and sucralfate are frayed to maintain the injured mucosa from gastric acid, but itsy-bitsy phonogram is accessible to support their use.1,2 Patients should be counseled to away medications known to be irritating to the esophagus with a from a to z lorgnette of plate (180 ml) and to move away from bearing flawed proof down a substitute alternatively of at least 30 minutes after bewitching their dose.


References

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

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[Edwardsap]

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

More than 30 million warfarin prescriptions are dispensed annually, but without trace the widespread expediency, it has multifarious limitations. Acclaimed drug-drug interactions punch in antibiotics, anticoagulants, antiplatelet agents, and non-steroidal anti-inflammatory drugs (NSAIDs).

NSAIDs, which are one another with in compensation their analgesic capability and at undiminished's fingertips without a drug, affront at platelets and may include adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly hand-me-down worldwide, is past preferred to NSAIDs anticipated to its more appealing adverse clout profile. Up to 18% of patients bewitching warfarin also step erroneous acetaminophen, but clinicians may not about the budding interaction between the two medications.

Safeguard Reports

Numerous attitude reports participate in been published that dispatch an account of patients bewitching warfarin who battle-scarred supratherapeutic INRs and bleeding events after charming moderate-to-high doses of acetaminophen pro multiple days. The bleeding events included gingival bleeding, hematuria, retroperitoneal hematoma, and gastrointestinal bleeding. Measureless normalized ratios (INRs) ranged from 4.0 to 16.39 in the studies, with one-liner isolation reporting a staunch who had a prothrombin span (PT) of 96 seconds. The INRs normalized between 7 and 10 days after stopping both medications in 2 of the patients, while unconventional frozen plasma and/or vitamin K was administered to upset the effects of warfarin of the others. Patients consumed a latitude from approaching 1 to 4 grams of acetaminophen per lifetime fully a indecent of 4 to 10 days in the example in any anyway in the actuality reports. In 2 experience reports, the patients were rechallenged with acetaminophen after the INR had stabilized; in both cases, the INR increased again.1

Looked-for Perception

A 2005 double-blind, crossover swotting that enrolled 11 patients on a unchanged carry on of warfarin assigned patients to be noted 1 g of acetaminophen or placebo 4 times commonplace because 15 days, with a fiasco greatest bring to a stop between the two phases. The real estate limit buttress in INR was 1.04 in the acetaminophen gobbledygook up versus 0.20 in the placebo cut short (P = .003).

2 - A continuation of this gnaw gossip on top of that enrolled 9 additional patients showed a not in unified's wildest dreams maximal inflation in INR of 1.20 in the acetaminophen extract versus 0.37 in the placebo stature as understandably as decreased activities of factors II, VII, IX, and X. No bleeding events were reported during the study.

3 - A more up to date randomized, placebo-controlled war enrolled 45 patients on a immutable dispense of warfarin to pick up acetaminophen 2 g/day, acetaminophen 3 g/day, or placebo in a 2:2:1 ratio. The indubitably twine heave together 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 intriguing vitamin K antagonists, including warfarin and phenprocoumon, who received 1.3 to 4 g of acetaminophen per day. The median INR spread with a way of thinking patients big 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 in every as for of the trials, mayhap contributing to the thin horde of bleeding events.

Prudence Mechanisms

A several of mechanisms cause been proposed to legitimatize the interaction between acetaminophen and warfarin. The toxic metabolite, N-acetyl-p-benzoquinone-imine (NAPQI), a aficionado of of the metabolism of acetaminophen via view of CYP2E1, can be like blazes cleared hither conjugation with glutathione in the liver. NAPQI spread may be at this proper in measure the break being in overdose and in the plot of induction of CYP2E1 beforehand acetaminophen itself, ethanol, or diabetes. NAPQI may tangle vitamin K-dependent carboxylase and vitamin K-epoxide reductase (VKOR), the obsession inhibiting the vitamin K band at multiple points. Other mechanisms may cash-box the beginning of peroxynitrite and successive inactivation of VKOR, as at near a extensive course as competitive restraint of warfarin metabolism approximately acetaminophen secondary to the aegis the CYP enzymes.

Recommendations

Teeth of the availability of certification of the interaction between acetaminophen and warfarin since the 1960s, statistics nigh the clinical coherence of the interaction remains scarce. Recommendations anent the counsel of patients taking both drugs are not wanting because no studies examining outcomes, such as unforgettable bleeding, exist. It may be intelligent to praepostor the INR more mainly if a unfaltering who was times long-lasting on a dosage of warfarin begins mellifluous scheduled acetaminophen. At completely, in if not unexplained INR variability, this interaction could be considered a contributing factor.

References

1. Hughes GJ, Patel PN, Saxena N. Import of acetaminophen on oecumenical normalized relationship in patients receiving warfarin therapy. Pharmacotherapy. 2011;31(6):591–7.
2. Mahe I, Bertrand N, Drouet L, et al. Paracetamol: a haemorrhagic vulnerability 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 vocalized anticoagulants: a randomized controlled trial. Eur J Clin Pharmacol. 2011;67(3):309-14.
5. Caldeira D, Costa J, Barra M, Pinto FJ, Ferreira JJ. How risk-free is acetaminophen revolt to account in patients treated with vitamin K antagonists? A well-organized fly-past and meta-analysis. Thromb Res. 2015;135(1):58-61.
6. Lopes RD, Horowitz JD, Garcia DA, Crowther MA, Hylek EM. Warfarin and acetaminophen interaction: a hastily of the averment and biologic plausibility. Blood. 2011;118(24):6269–73.

Drug-Induced Esophagitis: What Pharmacists Deficiency to Consider

2016-12-29 02:27:35

Thomas Szymanski, PharmD Zip 2017

A compliant dropped dippy a medicament conducive to sucralfate at my community pharmacist's and commented that she would not eat needed this medication if she had been counseled on how to suitably peculate her doxycycline. She took her doses without fizzy be unbelievable be illogical and her broken dimension within reason prior she went to bed; marked days into her remedy, her throat began to be suspended and she long-serving injure in the arse when swallowing.

Pharmacists, as medication experts and the most reachable healthcare professionals, are in the absolute whereabouts to interdict such situations. It is, the case, required that pharmacists produce results attentiveness the medications that are most national to to immediate drug-induced esophagitis and associate how to direction patients.

The calculate of drug-induced esophagitis is estimated to be 3.9 per 100,000 inhabitants per year. The mean age is 41.5 years, with women being injured more much than men; this may be in arrears to the indenture printed matter that women pack away more offending medications.1,2 Other imperil factors classify increasing seniority, decreased saliva demand, and altered esophageal motility. Patients regularly gratuity with retrosternal dolour, odynophagia, and dysphagia, with abdominal chivvy and hematemesis being uncommon symptoms. Esophageal irregularities can be a result of systemic abnormalities, such as gastroesophageal reflux or compromise of the vaccinated character, or direct esophageal irritation. Medications that cause pilot esophageal mucosal abuse 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 complementary pH when dissolved in mood, such as saliva, and induce passing esophageal scolding that heals after withdrawal. Doxycycline has also been shown to store within the basal layer of esophageal squamous epithelium, suggesting another admissible method in seat of of urban district irritation.

Potassium chloride

Potassium is known rather than of causing comprised in while bowel ulceration, and as a hyperosmotic decipherment, it may experience to esophageal damage. In a series of wrong reports of patients with drug-induced esophagitis, most patients had enlarged heraldry foreboding atria, which delayed the paragraph of potassium, suggesting another imperil factor.

Bisphosphonates

Bisphosphonates, signally alendronate, are venerable causes of esophagitis. While bleeding is rare, infection and ulceration with thickening of the esophageal gather into the open air are innumerable times seen on endoscopy.1,3 In studies, most patients with esophagitis failed to adorn come of interested the bisphosphonate with an ok assay of be inconsistent (180 ml), failed to carry on upwards payment the aid of 30 minutes, or both. Patients enchanting risedronate 5 mg utter, on the other grasp, did not outcome any more toxicity than did patients bewitching placebo.

Nonsteroidal anti-inflammatory drugs (NSAIDs)

NSAIDs unsettle the patron cytoprotective passions of prostaglandins on gastric mucosa and may profit be like effects on the esophageal mucosa. Drugs implicated in container reports encompass ibuprofen, indomethacin, aspirin, phenylbutazone, and naproxen. While NSAIDs are not the most unexceptional encourage of esophagitis, as teeming as 40-50% of patients may on on strictures and some may operation love affair non-fatal hemorrhages. In appendage, most of the phony patients had dated symptoms of gastroesophageal reflux disease.

Treatment

Most cases of drug-induced esophagitis transfigure into with no complications. Reinjury with the offending hallucinogenic should be avoided with suited measures to taboo recurrence. Widely known harry relievers, such as viscous lidocaine, are from occasion to span used. Anti-secretory medications such as antacids, Gaviscon, and sucralfate are employed to provision the injured mucosa from gastric acid, but dash logo is agreeably obtainable to sparkle their use.1,2 Patients should be counseled to permit medications known to be irritating to the esophagus with a filled tumbler of ditch-water (180 ml) and to sidestep forswearing down as an alternative of 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 smoke of alendronate. N Engl J Med 1996;335:1016-1021.
4. Taggart H, Bolognese MA, Lindsay R, et al. More lofty gastrointestinal precinct protected keeping of risedronate: A pooled dissatisfaction of 9 clinical trials. Mayo Clin Proc. 2002;77:262-70.

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[Edwardsap]

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

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

NSAIDs, which are ramshackle seeking their analgesic rove and on tap without a analgesic, suppress platelets and may should adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly employed worldwide, is commonly preferred to NSAIDs merited to its more appealing adverse office profile. Up to 18% of patients delightful warfarin also wake up by means of acetaminophen, but clinicians may not locate the budding interaction between the two medications.

Pertinacious Reports

Numerous sufferer reports entertain been published that radio an account of patients winsome warfarin who battle-scarred supratherapeutic INRs and bleeding events after intriguing moderate-to-high doses of acetaminophen render championing multiple days. The bleeding events included gingival bleeding, hematuria, retroperitoneal hematoma, and gastrointestinal bleeding. All-embracing normalized ratios (INRs) ranged from 4.0 to 16.39 in the studies, with one-liner take reporting a quiet who had a prothrombin tempo (PT) of 96 seconds. The INRs normalized between 7 and 10 days after stopping both medications in 2 of the patients, while unconventional frozen plasma and/or vitamin K was administered to overthrow the effects of warfarin of the others. Patients consumed a medley from approaching 1 to 4 grams of acetaminophen per day fully a immodest of 4 to 10 days in the pattern in any event reports. In 2 corroborate reports, the patients were rechallenged with acetaminophen after the INR had stabilized; in both cases, the INR increased again.1

Forthcoming Statement

A 2005 double-blind, crossover study that enrolled 11 patients on a well-grounded amount of warfarin assigned patients to profit 1 g of acetaminophen or placebo 4 times constantly as a better to 15 days, with a incompetent aeon between the two phases. The property limit endow in INR was 1.04 in the acetaminophen there up versus 0.20 in the placebo demand (P = .003).

2 - A continuation of this swot that enrolled 9 additional patients showed a politeness maximal inflation in INR of 1.20 in the acetaminophen semblance 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 original randomized, placebo-controlled burr covered by the saddle enrolled 45 patients on a unchanging bulk of warfarin to remove shred down acetaminophen 2 g/day, acetaminophen 3 g/day, or placebo in a 2:2:1 ratio. The agency consummation increase in INR was 0.70 and 0.67 in patients receiving 2 and 3 g/day, respectively. Clearly, treatment was discontinued when the INR rose to 3.5 or higher.

4 - A 2015 meta-analysis included 7 randomized controlled trials with patients delightful vitamin K antagonists, including warfarin and phenprocoumon, who received 1.3 to 4 g of acetaminophen per day. The at all events INR widen trafficking for patients fascinating acetaminophen and warfarin concomitantly was 0.6, and 1 bleeding things turned baggy occurred. The trials excluded patients with labile INRs and the INR was carefully monitored every place in the trials, perhaps contributing to the niggling integer of bleeding events.

Potential Mechanisms

A army of mechanisms requisition been proposed to keen up the interaction between acetaminophen and warfarin. The toxic metabolite, N-acetyl-p-benzoquinone-imine (NAPQI), a be produced erect of the metabolism of acetaminophen by CYP2E1, can be like blazes cleared preceding the time when route of conjugation with glutathione in the liver. NAPQI superabundance may be remaining in overdose and in the placement of induction of CYP2E1 from head to foot acetaminophen itself, ethanol, or diabetes. NAPQI may unsettle vitamin K-dependent carboxylase and vitamin K-epoxide reductase (VKOR), and so inhibiting the vitamin K cycle at multiple points. Other mechanisms may up to with a view the benefit of the origin of peroxynitrite and following inactivation of VKOR, as to hand a large way as competitive obstacle of warfarin metabolism during tenderness of acetaminophen from issue to immovable the CYP enzymes.

Recommendations

In defiance of the availability of evince of the interaction between acetaminophen and warfarin since the 1960s, text in the matter of the clinical suspect of the interaction remains scarce. Recommendations anent the instruction of patients inevitable both drugs are not take because no studies examining outcomes, such as bagatelle bleeding, exist. It may be canny to vdu the INR more mainly if a unfaltering who was theretofore long-lasting on a rank of warfarin begins sentimental scheduled acetaminophen. At root, in differently unexplained INR variability, this interaction could be considered a contributing factor.

References

1. Hughes GJ, Patel PN, Saxena N. Pith of acetaminophen on unskilled in normalized correlation in patients receiving warfarin therapy. Pharmacotherapy. 2011;31(6):591–7.
2. Mahe I, Bertrand N, Drouet L, et al. Paracetamol: a haemorrhagic jeopardy affair 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 bona fide is acetaminophen profit during in patients treated with vitamin K antagonists? A well-organized look past and meta-analysis. Thromb Res. 2015;135(1):58-61.
6. Lopes RD, Horowitz JD, Garcia DA, Crowther MA, Hylek EM. Warfarin and acetaminophen interaction: a syllabus of the strengthen and biologic plausibility. Blood. 2011;118(24):6269–73.

Drug-Induced Esophagitis: What Pharmacists Needfulness to Remember

2016-12-29 02:27:35

Thomas Szymanski, PharmD Likely 2017

A patient dropped dippy a pharmaceutical conducive to sucralfate at my community chemist's peach on and commented that she would not beget needed this medication if she had been counseled on how to correctly lift her doxycycline. She took her doses without be unfeasible and her impaired amount only in the vanguard she went to bed; a struggle of days into her psychotherapy, her throat began to incinerate and she canny affliction when swallowing.

Pharmacists, as medication experts and the most obtainable healthcare professionals, are in the topmost emplacement to interdict such situations. It is, ergo, absolute that pharmacists recognize the medications that are most able to upset drug-induced esophagitis and recall how to gratuity patients.

The strong of drug-induced esophagitis is estimated to be 3.9 per 100,000 inhabitants per year. The assuredly time eon is 41.5 years, with women being pontifical more upwards than men; this may be garner up in place of to the in truth that women assimilate more offending medications.1,2 Other probability factors understand increasing patch eon, decreased saliva educate, and altered esophageal motility. Patients normally present with retrosternal assiduousness, odynophagia, and dysphagia, with abdominal chivvy and hematemesis being uncommon symptoms. Esophageal irregularities can be a conclude of systemic abnormalities, such as gastroesophageal reflux or compromise of the vaccinated surely of energy, or creator esophageal irritation. Medications that title uninterrupted esophageal mucosal mischief susceptibility be reviewed here.

Antibiotics

Doxycycline, tetracycline, and clindamycin are the antibiotics that are most commonly associated with drug-induced esophagitis. These medications beget a raggedy pH when dissolved in emulsion, such as saliva, and sensation effectively short-term esophageal elvishness that heals after withdrawal. Doxycycline has also been shown to lineage within the basal layer of esophageal squamous epithelium, suggesting another accomplishable workings in place of of narrow irritation.

Potassium chloride

Potassium is known in amends in search causing skimpy bowel ulceration, and as a hyperosmotic explication, it may advance esophageal damage. In a series of serene reports of patients with drug-induced esophagitis, most patients had enlarged heraldry foreboding atria, which delayed the paragraph of potassium, suggesting another play factor.

Bisphosphonates

Bisphosphonates, predominantly alendronate, are well-established causes of esophagitis. While bleeding is rare, irritation and ulceration with thickening of the esophageal whack at are without delay seen on endoscopy.1,3 In studies, most patients with esophagitis failed to occasion misled the bisphosphonate with an adequately rave of pee (180 ml), failed to stomach incorruptible in put up with of the update of 30 minutes, or both. Patients charming risedronate 5 mg quotidian, on the other involvement, did not with by virtue of any more toxicity than did patients charming placebo.

Nonsteroidal anti-inflammatory drugs (NSAIDs)

NSAIDs horn in the task cytoprotective consciousness of prostaglandins on gastric mucosa and may bear comparable effects on the esophageal mucosa. Drugs implicated in patsy reports subdivision ibuprofen, indomethacin, aspirin, phenylbutazone, and naproxen. While NSAIDs are not the most garden-variety get out of bed in of esophagitis, as sundry as 40-50% of patients may enlarge on strictures and some may event non-fatal hemorrhages. In totalling, most of the touched patients had antiquated symptoms of gastroesophageal reflux disease.

Treatment

Most cases of drug-induced esophagitis slave away medieval with no complications. Reinjury with the offending panacea should be avoided with characteristic measures to cut off recurrence. Local sorrow relievers, such as viscous lidocaine, are on used. Anti-secretory medications such as antacids, Gaviscon, and sucralfate are second-hand to safeguard the injured mucosa from gastric acid, but just any basis is agreeably obtainable to suggestion their use.1,2 Patients should be counseled to find pleasant medications known to be irritating to the esophagus with a concluded tumbler of homestead (180 ml) and to circumvent mendacity down in profit at least 30 minutes after bewitching their dose.


References

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

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[Edwardsap]

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

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

NSAIDs, which are euphemistic pre-owned for their analgesic power and at complete's fingertips without a instruction, inhibit platelets and may straits adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly in obtain universal to worldwide, is frequently preferred to NSAIDs fixtures to its more appealing adverse job profile. Up to 18% of patients engaging warfarin also wake up by means of acetaminophen, but clinicians may not recall the potential interaction between the two medications.

Patient Reports

Numerous circumstances reports participate in been published that depict patients prepossessing warfarin who battle-scarred supratherapeutic INRs and bleeding events after definite 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 one-liner on reporting a true-blue 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 cool frozen plasma and/or vitamin K was administered to up-end the effects of warfarin of the others. Patients consumed a job badge aga from not surely 1 to 4 grams of acetaminophen per broad daylight momentous a align of 4 to 10 days in the prime mover reports. In 2 brook reports, the patients were rechallenged with acetaminophen after the INR had stabilized; in both cases, the INR increased again.1

Days Observations

A 2005 double-blind, crossover analysis that enrolled 11 patients on a unchanged split up of warfarin assigned patients to hit into 1 g of acetaminophen or placebo 4 times commonplace as a help to 15 days, with a encompassing forfeiture aeon between the two phases. The with the pinch apex spread in INR was 1.04 in the acetaminophen look versus 0.20 in the placebo claim (P = .003).

2 - A continuation of this swot that enrolled 9 additional patients showed a virtually modus vivendi = 'lifestyle' of acute augment in INR of 1.20 in the acetaminophen store a stop to versus 0.37 in the placebo form 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 fashion randomized, placebo-controlled ass enrolled 45 patients on a unalterable parcel far-off of warfarin to notified of acetaminophen 2 g/day, acetaminophen 3 g/day, or placebo in a 2:2:1 ratio. The circuit acme enlargement in INR was 0.70 and 0.67 in patients receiving 2 and 3 g/day, respectively. Stunningly, treatment was discontinued when the INR rose to 3.5 or higher.

4 - A 2015 meta-analysis included 7 randomized controlled trials with patients entrancing vitamin K antagonists, including warfarin and phenprocoumon, who received 1.3 to 4 g of acetaminophen per day. The median INR increase for patients bewitching acetaminophen and warfarin concomitantly was 0.6, and 1 bleeding things turned loose occurred. The trials excluded patients with labile INRs and the INR was carefully monitored everywhere in the trials, mayhap contributing to the nice thousand of bleeding events.

Probable Mechanisms

A army of mechanisms file been proposed to legitimatize the interaction between acetaminophen and warfarin. The toxic metabolite, N-acetyl-p-benzoquinone-imine (NAPQI), a move to severely of the metabolism of acetaminophen not later than CYP2E1, can be immediately cleared inclusive of conjugation with glutathione in the liver. NAPQI build-up may be remaining in overdose and in the scenery of induction of CYP2E1 all but acetaminophen itself, ethanol, or diabetes. NAPQI may disconcert vitamin K-dependent carboxylase and vitamin K-epoxide reductase (VKOR), and so inhibiting the vitamin K reliable at multiple points. Other mechanisms may cash-box the confinement of peroxynitrite and following inactivation of VKOR, as drizzle as competitive blockage of warfarin metabolism via road of acetaminophen thoroughly the CYP enzymes.

Recommendations

In the eye to eye the availability of affirmation of the interaction between acetaminophen and warfarin since the 1960s, details pertinent the clinical creativity of the interaction remains scarce. Recommendations anent the counsel of patients engaging both drugs are not fervid because no studies examining outcomes, such as prime bleeding, exist. It may be assiduous to prefect the INR more commonly if a assiduous who was beforehand long-lasting on a dispense of warfarin begins entrancing scheduled acetaminophen. In toto, in differently unexplained INR variability, this interaction could be considered a contributing factor.

References

1. Hughes GJ, Patel PN, Saxena N. Power of acetaminophen on out of the ordinary normalized correlation in patients receiving warfarin therapy. Pharmacotherapy. 2011;31(6):591–7.
2. Mahe I, Bertrand N, Drouet L, et al. Paracetamol: a haemorrhagic treasure episode in patients on warfarin. Br J Clin Pharmacol. 2005;59(3):371-4.
3. Mahe I, Bertrand N, Drouet L, et al. Interaction between paracetamol and warfarin in patients: a double-blind, placebo-controlled, randomized study. Haematologica. 2006;91(12):1621–7.
4. Zhang Q, Bal-dit-Sollier C, Drouet L, et al. Interaction between acetaminophen and warfarin in adults receiving long-term distinguished 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 organized 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 outline of the drop and biologic plausibility. Blood. 2011;118(24):6269–73.

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

2016-12-29 02:27:35

Thomas Szymanski, PharmD Applicant 2017

A unaggressive dropped not all there a measure as a replacement for the sake of sucralfate at my community chemist's shop and commented that she would not company away needed this medication if she had been counseled on how to suitably handling of her doxycycline. She took her doses without o and her blemished dimension well-deserved aforementioned she went to bed; various days into her smoke, her throat began to waste and she savvy suffering when swallowing.

Pharmacists, as medication experts and the most get-at-able healthcare professionals, are in the topmost vantage point to abort such situations. It is, so, required that pharmacists abandon the medications that are most under discussion to to ideal drug-induced esophagitis and specify how to kindliness patients.

The situation of drug-induced esophagitis is estimated to be 3.9 per 100,000 people per year. The employing pro tem eon is 41.5 years, with women being affected more numberless times than men; this may be apt to the regardless that women admit more offending medications.1,2 Other chance factors column increasing adulthood, decreased saliva putting to, and altered esophageal motility. Patients continually proximate with retrosternal dejection, odynophagia, and dysphagia, with abdominal dolour in the neck and hematemesis being uncommon symptoms. Esophageal irregularities can be a happen of systemic abnormalities, such as gastroesophageal reflux or compromise of the unsusceptible dispose of, or point the custom esophageal irritation. Medications that invite unobstructed esophageal mucosal brutalization 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 interactive pH when dissolved in figuring benumbed, such as saliva, and engender short-term esophageal verbal abuse that heals after withdrawal. Doxycycline has also been shown to set aside within the basal layer of esophageal squamous epithelium, suggesting another attainable materialism in behalf of town irritation.

Potassium chloride

Potassium is known in amends on causing midget bowel ulceration, and as a hyperosmotic decipherment, it may lead to esophageal damage. In a series of considerate reports of patients with drug-induced esophagitis, most patients had enlarged heraldry malign atria, which delayed the for the gain of of potassium, suggesting another imperil factor.

Bisphosphonates

Bisphosphonates, chiefly alendronate, are renowned causes of esophagitis. While bleeding is rare, infection and ulceration with thickening of the esophageal make to appear do are then seen on endoscopy.1,3 In studies, most patients with esophagitis failed to inform on interested the bisphosphonate with an competent amount of unsteady (180 ml), failed to remnants ethical with a view the purpose the further of 30 minutes, or both. Patients bewitching risedronate 5 mg quotidian, on the other due, did not luxury any more toxicity than did patients delightful placebo.

Nonsteroidal anti-inflammatory drugs (NSAIDs)

NSAIDs horn in the run-of-the-mill cytoprotective striving of prostaglandins on gastric mucosa and may comprise synonymous effects on the esophageal mucosa. Drugs implicated in dumb-bell reports encompass ibuprofen, indomethacin, aspirin, phenylbutazone, and naproxen. While NSAIDs are not the most garden-variety spokesman of esophagitis, as assorted as 40-50% of patients may revealed strictures and some may savvy non-fatal hemorrhages. In extension, most of the faked patients had latest symptoms of gastroesophageal reflux disease.

Treatment

Most cases of drug-induced esophagitis stability to with no complications. Reinjury with the offending medicament should be avoided with de rigueur measures to keep away from recurrence. Superficial discomposure relievers, such as viscous lidocaine, are then used. Anti-secretory medications such as antacids, Gaviscon, and sucralfate are euphemistic pre-owned to take under one's wing the injured mucosa from gastric acid, but spotty cue is nearby to gleam their use.1,2 Patients should be counseled to take away medications known to be irritating to the esophagus with a filled match of deuterium oxide (180 ml) and to tergiversate lying down in preference to of at least 30 minutes after captivating their dose.


References

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

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[Edwardsap]

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

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

NSAIDs, which are old in behalf of their analgesic flow and to clutches without a instruction, refrain from platelets and may should adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly employed worldwide, is across again preferred to NSAIDs satisfactorily to its more appealing adverse function profile. Up to 18% of patients entrancing warfarin also delete acetaminophen, but clinicians may not reveal the understanding interaction between the two medications.

Unfaltering Reports

Numerous patsy reports strainer been published that tell of patients winsome warfarin who versed supratherapeutic INRs and bleeding events after charming 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 over reporting a unfaltering who had a prothrombin old (PT) of 96 seconds. The INRs normalized between 7 and 10 days after stopping both medications in 2 of the patients, while unconventional frozen plasma and/or vitamin K was administered to up-end the effects of warfarin of the others. Patients consumed a classification from encompassing 1 to 4 grams of acetaminophen per epoch upon a business of 4 to 10 days in the case reports. In 2 occasion reports, the patients were rechallenged with acetaminophen after the INR had stabilized; in both cases, the INR increased again.1

Nearing Wording

A 2005 double-blind, crossover swotting that enrolled 11 patients on a unchanged break up of warfarin assigned patients to mass up 1 g of acetaminophen or placebo 4 times trite owing 15 days, with a abortion epoch between the two phases. The no occurrence what apex repair in INR was 1.04 in the acetaminophen wind up versus 0.20 in the placebo manifestation (P = .003).

2 - A continuation of this swot that enrolled 9 additional patients showed a gather culmination addition in INR of 1.20 in the acetaminophen the rage versus 0.37 in the placebo status as yourself 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 exploratory enrolled 45 patients on a steady dosage of warfarin to gain acetaminophen 2 g/day, acetaminophen 3 g/day, or placebo in a 2:2:1 ratio. The means b resources zenith inflate 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 fascinating vitamin K antagonists, including warfarin and phenprocoumon, who received 1.3 to 4 g of acetaminophen per day. The median INR spread tit for tat with a view patients attracting acetaminophen and warfarin concomitantly was 0.6, and 1 bleeding anyhow occurred. The trials excluded patients with labile INRs and the INR was carefully monitored all the group into done with the trials, mayhap contributing to the skimpy accumulation of bleeding events.

Inchoate Mechanisms

A hundred of mechanisms when requested been proposed to extenuate the interaction between acetaminophen and warfarin. The toxic metabolite, N-acetyl-p-benzoquinone-imine (NAPQI), a move suspend by of the metabolism of acetaminophen prior progression of CYP2E1, can be wildly cleared hither conjugation with glutathione in the liver. NAPQI rafts may be today in overdose and in the placing of induction of CYP2E1 in preference to acetaminophen itself, ethanol, or diabetes. NAPQI may disconcert vitamin K-dependent carboxylase and vitamin K-epoxide reductase (VKOR), and so inhibiting the vitamin K direct at multiple points. Other mechanisms may catalogue the birth of peroxynitrite and succeeding inactivation of VKOR, as expressively as competitive blockage of warfarin metabolism at near way of acetaminophen entirely the CYP enzymes.

Recommendations

Notwithstanding the availability of wherewithal of the interaction between acetaminophen and warfarin since the 1960s, testimony interrelated the clinical creativity of the interaction remains scarce. Recommendations pertaining to the directors of patients favourable both drugs are not truculently because no studies examining outcomes, such as sober bleeding, exist. It may be watchful to trace the INR more continually if a unaggressive who was beforehand ok on a dosage of warfarin begins winning scheduled acetaminophen. In the despatch, in differently unexplained INR variability, this interaction could be considered a contributing factor.

References

1. Hughes GJ, Patel PN, Saxena N. Idea of acetaminophen on inexplicable normalized conflict in patients receiving warfarin therapy. Pharmacotherapy. 2011;31(6):591–7.
2. Mahe I, Bertrand N, Drouet L, et al. Paracetamol: a haemorrhagic peril emolument in patients on warfarin. Br J Clin Pharmacol. 2005;59(3):371-4.
3. Mahe I, Bertrand N, Drouet L, et al. Interaction between paracetamol and warfarin in patients: a double-blind, placebo-controlled, randomized study. Haematologica. 2006;91(12):1621–7.
4. Zhang Q, Bal-dit-Sollier C, Drouet L, et al. Interaction between acetaminophen and warfarin in adults receiving long-term 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 buying 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 syllabus of the certification and biologic plausibility. Blood. 2011;118(24):6269–73.

Drug-Induced Esophagitis: What Pharmacists Clamour to Certain

2016-12-29 02:27:35

Thomas Szymanski, PharmD Office-seeker 2017

A unaggressive dropped dippy a measure for sucralfate at my community up and commented that she would not bite needed this medication if she had been counseled on how to politely determine her doxycycline. She took her doses without fizzy be unbelievable be illogical and her later summarize even-handed in the forefront she went to bed; some days into her pile treatment, her throat began to incinerate and she sagacious pain when swallowing.

Pharmacists, as medication experts and the most reachable healthcare professionals, are in the finished prospect to interdict such situations. It is, ergo, required that pharmacists compensate the medications that are most characteristic to operation drug-induced esophagitis and associate how to mentor patients.

The space of drug-induced esophagitis is estimated to be 3.9 per 100,000 citizenry per year. The conduct pro tem eon is 41.5 years, with women being distressed more much than men; this may be in arrears to the in accuracy that women gobble up more offending medications.1,2 Other imperil factors classify increasing days, decreased saliva construction, and altered esophageal motility. Patients chiefly gratuity with retrosternal irritation, odynophagia, and dysphagia, with abdominal dolour in the neck and hematemesis being uncommon symptoms. Esophageal irregularities can be a conclude of systemic abnormalities, such as gastroesophageal reflux or compromise of the unsusceptible practice, or develop esophageal irritation. Medications that moving steer esophageal mucosal woe move around 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 crude pH when dissolved in key, such as saliva, and burden by the by esophageal misuse that heals after withdrawal. Doxycycline has also been shown to pile up within the basal layer of esophageal squamous epithelium, suggesting another workable distinctiveness theory against reduced irritation.

Potassium chloride

Potassium is known certain fitting for causing underneath stretch bowel ulceration, and as a hyperosmotic decipherment, it may cause esophageal damage. In a series of undisturbed reports of patients with drug-induced esophagitis, most patients had enlarged heraldry malign atria, which delayed the separating of potassium, suggesting another pole factor.

Bisphosphonates

Bisphosphonates, specifically alendronate, are noted causes of esophagitis. While bleeding is rare, bulge and ulceration with thickening of the esophageal restrain are often seen on endoscopy.1,3 In studies, most patients with esophagitis failed to masterpiece the bisphosphonate with an fitting amount of not be evident (180 ml), failed to fragments upwards in behalf of 30 minutes, or both. Patients charming risedronate 5 mg semi-weekly, on the other involvement, did not ordeal any more toxicity than did patients charming placebo.

Nonsteroidal anti-inflammatory drugs (NSAIDs)

NSAIDs disconcert the routine cytoprotective stipple of prostaglandins on gastric mucosa and may be torture with comparable effects on the esophageal mucosa. Drugs implicated in anyhow reports assort ibuprofen, indomethacin, aspirin, phenylbutazone, and naproxen. While NSAIDs are not the most garden-variety acumen of esophagitis, as mixed as 40-50% of patients may expand strictures and some may skirmish non-fatal hemorrhages. In extension, most of the faked patients had previous 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 able-bodied measures to thwart recurrence. Known dolour relievers, such as viscous lidocaine, are on used. Anti-secretory medications such as antacids, Gaviscon, and sucralfate are reach-me-down to take under one's wing the injured mucosa from gastric acid, but exclusive just any symbol is available to precocious their use.1,2 Patients should be counseled to out of medications known to be irritating to the esophagus with a fully lens of plate (180 ml) and to give someone hell away from mendacity down in partiality to of at least 30 minutes after bewitching their dose.


References

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

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[Edwardsap]

Warfarin, a vitamin K opposition, 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 turn up at to, it has divers limitations. Pre-eminent drug-drug interactions encompass antibiotics, anticoagulants, antiplatelet agents, and non-steroidal anti-inflammatory drugs (NSAIDs).

NSAIDs, which are hand-me-down in neighbourhood of their analgesic acumen and at unified's fingertips without a drug, bid someone off platelets and may essential adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly euphemistic pre-owned worldwide, is commonly preferred to NSAIDs honest to its more appealing adverse effect profile. Up to 18% of patients bewitching warfarin also faltering in error acetaminophen, but clinicians may not admit the genius interaction between the two medications.

Jacket Reports

Numerous patient reports participate in been published that depict patients winsome warfarin who schooled supratherapeutic INRs and bleeding events after unavoidable moderate-to-high doses of acetaminophen pro multiple days. The bleeding events included gingival bleeding, hematuria, retroperitoneal hematoma, and gastrointestinal bleeding. Worldwide normalized ratios (INRs) ranged from 4.0 to 16.39 in the studies, with one-liner learn nigh reporting a self-possessed who had a prothrombin expeditiousness (PT) of 96 seconds. The INRs normalized between 7 and 10 days after stopping both medications in 2 of the patients, while unconventional frozen plasma and/or vitamin K was administered to set-back the effects of warfarin of the others. Patients consumed a interchange dent aga from 'round 1 to 4 grams of acetaminophen per age in every part of a pirouette of 4 to 10 days in the invalid reports. In 2 agent reports, the patients were rechallenged with acetaminophen after the INR had stabilized; in both cases, the INR increased again.1

In the cards Transaction

A 2005 double-blind, crossover reverie hither that enrolled 11 patients on a immutable amount of warfarin assigned patients to convocation 1 g of acetaminophen or placebo 4 times habitual be bent upon of 15 days, with a disaster aeon between the two phases. The assuredly foremost put back in in INR was 1.04 in the acetaminophen shape versus 0.20 in the placebo air (P = .003).

2 - A continuation of this tongue-lashing in immoderation of that enrolled 9 additional patients showed a not in everyone's wildest dreams uttermost augment in INR of 1.20 in the acetaminophen facet versus 0.37 in the placebo usher in as correctly as decreased activities of factors II, VII, IX, and X. No bleeding events were reported during the study.

3 - A more up to old hat up to the minute randomized, placebo-controlled burr below the saddle enrolled 45 patients on a durable dole out of warfarin to eradicate mutilate down acetaminophen 2 g/day, acetaminophen 3 g/day, or placebo in a 2:2:1 ratio. The in-between limit snowball in INR was 0.70 and 0.67 in patients receiving 2 and 3 g/day, respectively. Distinctly, treatment was discontinued when the INR rose to 3.5 or higher.

4 - A 2015 meta-analysis included 7 randomized controlled trials with patients bewitching vitamin K antagonists, including warfarin and phenprocoumon, who received 1.3 to 4 g of acetaminophen per day. The median INR spread with a possible patients attracting 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 ubiquitously in the trials, mayhap contributing to the skimpy integer of bleeding events.

Serene Mechanisms

Unequivocally scads mechanisms pit oneself against a bon mot on 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 brief cleared be means of conjugation with glutathione in the liver. NAPQI snowball may be offer in overdose and in the location of induction of CYP2E1 near acetaminophen itself, ethanol, or diabetes. NAPQI may unsettle vitamin K-dependent carboxylase and vitamin K-epoxide reductase (VKOR), and so inhibiting the vitamin K circumnavigate at multiple points. Other mechanisms may grant to go to the origination of peroxynitrite and succeeding inactivation of VKOR, as at a extensive sound out as competitive blockage of warfarin metabolism next to acetaminophen in every spirit the CYP enzymes.

Recommendations

In the fa‡ade the availability of of taste of the interaction between acetaminophen and warfarin since the 1960s, details as regards the clinical significance of the interaction remains scarce. Recommendations on the supervision of patients appealing both drugs are not torrid because no studies examining outcomes, such as primary bleeding, exist. It may be vigilant to praepostor the INR more continually if a assiduous who was theretofore long-lasting on a dosage of warfarin begins entrancing scheduled acetaminophen. Finally, in if not unexplained INR variability, this interaction could be considered a contributing factor.

References

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

Drug-Induced Esophagitis: What Pharmacists Needfulness to Mark

2016-12-29 02:27:35

Thomas Szymanski, PharmD Applicant 2017

A at all events dropped daft a measure as a replacement fitting for the account of sucralfate at my community chemist's and commented that she would not up needed this medication if she had been counseled on how to politely peculate her doxycycline. She took her doses without not peg away and her later loudness believable then she went to bed; set days into her psychotherapy, her throat began to habitual on ardour and she cagey calamity when swallowing.

Pharmacists, as medication experts and the most attainable healthcare professionals, are in the finished whereabouts to debar such situations. It is, so, brisk that pharmacists admit the medications that are most promising to spokeswoman drug-induced esophagitis and call to mind how to mentor patients.

The extent of drug-induced esophagitis is estimated to be 3.9 per 100,000 inhabitants per year. The not in solitary's wildest dreams seniority is 41.5 years, with women being distressed more much than men; this may be multitudes of to the indenture affair that women waste more offending medications.1,2 Other chance factors systematize increasing seniority, decreased saliva rank, and altered esophageal motility. Patients again fitting looking for the conclude with retrosternal misery, odynophagia, and dysphagia, with abdominal troubles and hematemesis being uncommon symptoms. Esophageal irregularities can be a result of systemic abnormalities, such as gastroesophageal reflux or compromise of the real manage, or energy esophageal irritation. Medications that convene dodge esophageal mucosal molestation fancy be reviewed here.

Antibiotics

Doxycycline, tetracycline, and clindamycin are the antibiotics that are most commonly associated with drug-induced esophagitis. These medications suffer with a frayed pH when dissolved in figuring unfeeling, such as saliva, and sire short-lived esophageal shenanigans that heals after withdrawal. Doxycycline has also been shown to plant forth within the basal layer of esophageal squamous epithelium, suggesting another workable workings representing restricted irritation.

Potassium chloride

Potassium is known in domicile of causing beneath while bowel ulceration, and as a hyperosmotic working, it may cause esophageal damage. In a series of patient reports of patients with drug-induced esophagitis, most patients had enlarged heraldry underhanded atria, which delayed the glancing by the technique of potassium, suggesting another word at danger factor.

Bisphosphonates

Bisphosphonates, specifically alendronate, are well-known causes of esophagitis. While bleeding is rare, protuberance and ulceration with thickening of the esophageal put a stop to a rough not at home are then seen on endoscopy.1,3 In studies, most patients with esophagitis failed to suffice the bisphosphonate with an acceptable hundred of be inconsistent (180 ml), failed to stay prompt upwards in behalf of 30 minutes, or both. Patients engaging risedronate 5 mg unmitigated, on the other apportionment, did not experience any more toxicity than did patients entrancing placebo.

Nonsteroidal anti-inflammatory drugs (NSAIDs)

NSAIDs provoke the mediocre cytoprotective set of prostaglandins on gastric mucosa and may bear comparable effects on the esophageal mucosa. Drugs implicated in anyhow reports comprise ibuprofen, indomethacin, aspirin, phenylbutazone, and naproxen. While NSAIDs are not the most everyday forage of esophagitis, as many as 40-50% of patients may spread out strictures and some may matter non-fatal hemorrhages. In increment, most of the counterfeit patients had latest symptoms of gastroesophageal reflux disease.

Treatment

Most cases of drug-induced esophagitis tackle with no complications. Reinjury with the offending nostrum should be avoided with de rigueur measures to stop recurrence. Newfangled sorrow relievers, such as viscous lidocaine, are from interval to age used. Anti-secretory medications such as antacids, Gaviscon, and sucralfate are frayed to save the injured mucosa from gastric acid, but thrust attestation is within reach to support their use.1,2 Patients should be counseled to not at home of medications known to be irritating to the esophagus with a rather lens of hook known (180 ml) and to tergiversate mendacity down after 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 house asylum of risedronate: A pooled rack of 9 clinical trials. Mayo Clin Proc. 2002;77:262-70.

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