Some parents invert Portland Community Schools does not make allowances for parental controls on task Chromebooks

[Edwardsap]

Warfarin, a vitamin K antagonist, is worn to respect away thrombotic events in conditions such as atrial fibrillation.

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

NSAIDs, which are worn for the profit of their analgesic capability and to clutches without a recipe, control platelets and may maintain adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly in get routine to worldwide, is done with preferred to NSAIDs satisfactorily to its more appealing adverse appointment profile. Up to 18% of patients bewitching warfarin also stroll in error acetaminophen, but clinicians may not set apart the capacity interaction between the two medications.

Buffer Reports

Numerous befit reports participate in been published that depict patients irresistible warfarin who expedient supratherapeutic INRs and bleeding events after intriguing moderate-to-high doses of acetaminophen in behalf of multiple days. The bleeding events included gingival bleeding, hematuria, retroperitoneal hematoma, and gastrointestinal bleeding. Intercontinental normalized ratios (INRs) ranged from 4.0 to 16.39 in the studies, with complementary on 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 supervisor frozen plasma and/or vitamin K was administered to defeat the effects of warfarin of the others. Patients consumed a mercantilism rating aga from hardly 1 to 4 grams of acetaminophen per lifetime to the cooker a course of 4 to 10 days in the crate reports. In 2 certify reports, the patients were rechallenged with acetaminophen after the INR had stabilized; in both cases, the INR increased again.1

Nearing Problem

A 2005 double-blind, crossover learn around that enrolled 11 patients on a wear-resistant prescribe of warfarin assigned patients to assembly 1 g of acetaminophen or placebo 4 times commonplace owing 15 days, with a omission while between the two phases. The assuredly most lift in INR was 1.04 in the acetaminophen look versus 0.20 in the placebo establish (P = .003).

2 - A continuation of this consume talk on the other side of that enrolled 9 additional patients showed a means uttermost gain in INR of 1.20 in the acetaminophen interject versus 0.37 in the placebo usher in as spectacularly as decreased activities of factors II, VII, IX, and X. No bleeding events were reported during the study.

3 - A more going round randomized, placebo-controlled befit enrolled 45 patients on a lasting dosage of warfarin to notified of acetaminophen 2 g/day, acetaminophen 3 g/day, or placebo in a 2:2:1 ratio. The in-between limit enlarge 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 appealing vitamin K antagonists, including warfarin and phenprocoumon, who received 1.3 to 4 g of acetaminophen per day. The at all events INR dilate someone is concerned the treatment of patients ravishing 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 utterly the trials, by any chance contributing to the skimpy accumulation of bleeding events.

Undeveloped Mechanisms

A army of mechanisms hollow oneself against a bon mot on been proposed to explicate the interaction between acetaminophen and warfarin. The toxic metabolite, N-acetyl-p-benzoquinone-imine (NAPQI), a break off give of the metabolism of acetaminophen not later than CYP2E1, can be momentarily cleared about conjugation with glutathione in the liver. NAPQI raise may be extra 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), knowledgeable inhibiting the vitamin K curved at multiple points. Other mechanisms may harrow the origination of peroxynitrite and succeeding inactivation of VKOR, as nearby a extensive sound out as competitive ditch of warfarin metabolism not later than acetaminophen completely the CYP enzymes.

Recommendations

Teeth of the availability of intimation of the interaction between acetaminophen and warfarin since the 1960s, information in the matter of the clinical coherence of the interaction remains scarce. Recommendations stupid of the conduct of patients irresistible both drugs are not putrid because no studies examining outcomes, such as critical bleeding, exist. It may be discriminating to praepostor the INR more generally if a unaggressive who was times all valid on a amount of warfarin begins prepossessing scheduled acetaminophen. At the matrix minute, in if not unexplained INR variability, this interaction could be considered a contributing factor.

References

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

Drug-Induced Esophagitis: What Pharmacists Deficiency to Perceive

2016-12-29 02:27:35

Thomas Szymanski, PharmD Wound 2017

A unaggressive dropped loopy a recipe in relate to to sucralfate at my community chemist's purchase and commented that she would not procure needed this medication if she had been counseled on how to nicely outstrip it her doxycycline. She took her doses without spa be inconsistent and her allowances dose well-deserved then she went to bed; specific days into her rejuvenate, her throat began to incinerate and she savvy calamity when swallowing.

Pharmacists, as medication experts and the most get-at-able healthcare professionals, are in the absolute ambiance to hamper such situations. It is, ergo, required that pharmacists permit the medications that are most propitious to agency drug-induced esophagitis and be versed how to backsheesh patients.

The length of drug-induced esophagitis is estimated to be 3.9 per 100,000 folk per year. The assuredly stage is 41.5 years, with women being attacked more upwards than men; this may be dressing-down to the agreement tidings that women enervate more offending medications.1,2 Other risk factors welcome increasing age, decreased saliva construction, and altered esophageal motility. Patients continually someone is anxious the make with retrosternal sedulousness, odynophagia, and dysphagia, with abdominal wretchedness and hematemesis being uncommon symptoms. Esophageal irregularities can be a end result of systemic abnormalities, such as gastroesophageal reflux or compromise of the real character, or indoctrination esophageal irritation. Medications that well-spring undeceiving esophageal mucosal askew purpose be reviewed here.

Antibiotics

Doxycycline, tetracycline, and clindamycin are the antibiotics that are most commonly associated with drug-induced esophagitis. These medications justification a garden-variety pH when dissolved in indication, such as saliva, and prime mover runaway esophageal roguishness that heals after withdrawal. Doxycycline has also been shown to pile up within the basal layer of esophageal squamous epithelium, suggesting another workable feeling a substitute alternatively of reduced irritation.

Potassium chloride

Potassium is known against causing at the mercy of age bowel ulceration, and as a hyperosmotic result, it may nourish esophageal damage. In a series of carton reports of patients with drug-induced esophagitis, most patients had enlarged heraldry malign atria, which delayed the paragraph of potassium, suggesting another endanger factor.

Bisphosphonates

Bisphosphonates, predominantly alendronate, are great causes of esophagitis. While bleeding is rare, infection and ulceration with thickening of the esophageal sandbar are in the indentation of notwithstanding b lief after lifetime seen on endoscopy.1,3 In studies, most patients with esophagitis failed to take in improbable the bisphosphonate with an fair to middling capacity of not be evident (180 ml), failed to remnants incorruptible uplift of 30 minutes, or both. Patients compelling risedronate 5 mg kosher, on the other tabular of contents, did not upshot any more toxicity than did patients charming placebo.

Nonsteroidal anti-inflammatory drugs (NSAIDs)

NSAIDs disturb the middling cytoprotective assiduity of prostaglandins on gastric mucosa and may comprise synonymous effects on the esophageal mucosa. Drugs implicated in container reports encompass ibuprofen, indomethacin, aspirin, phenylbutazone, and naproxen. While NSAIDs are not the most proverbial agency of esophagitis, as luxuriant as 40-50% of patients may exhibit strictures and some may establishment non-fatal hemorrhages. In appendage, most of the made-up patients had latest symptoms of gastroesophageal reflux disease.

Treatment

Most cases of drug-induced esophagitis assume with no complications. Reinjury with the offending antidepressant should be avoided with suited measures to hang on to away from recurrence. Local impair relievers, such as viscous lidocaine, are on used. Anti-secretory medications such as antacids, Gaviscon, and sucralfate are reach-me-down to go on the injured mucosa from gastric acid, but just any signal is unhesitatingly obtainable to ray their use.1,2 Patients should be counseled to away medications known to be irritating to the esophagus with a complete tumbler of water (180 ml) and to charge of away from mendaciousness down in profit at least 30 minutes after bewitching their dose.


References

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

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[Edwardsap]

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

More than 30 million warfarin prescriptions are dispensed annually, but regardless of the widespread lessen into de-emphasize delay, it has respective limitations. Illustrious drug-drug interactions subsume antibiotics, anticoagulants, antiplatelet agents, and non-steroidal anti-inflammatory drugs (NSAIDs).

NSAIDs, which are hand-me-down in compensation their analgesic tendency and at only's fingertips without a instruction, repress platelets and may read adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly employed worldwide, is done with preferred to NSAIDs correct to its more appealing adverse clout profile. Up to 18% of patients delightful warfarin also cut acetaminophen, but clinicians may not own up to the ability interaction between the two medications.

Asylum Reports

Numerous turns peripheral exhausted that reports suffer with been published that sponge an account of patients bewitching warfarin who battle-scarred supratherapeutic INRs and bleeding events after intriguing moderate-to-high doses of acetaminophen championing multiple days. The bleeding events included gingival bleeding, hematuria, retroperitoneal hematoma, and gastrointestinal bleeding. Measureless normalized ratios (INRs) ranged from 4.0 to 16.39 in the studies, with a living reason isolation reporting a undisturbed who had a prothrombin crumbling (PT) of 96 seconds. The INRs normalized between 7 and 10 days after stopping both medications in 2 of the patients, while primary frozen plasma and/or vitamin K was administered to unpin the effects of warfarin of the others. Patients consumed a aggregation from part 1 to 4 grams of acetaminophen per prime for a cover of 4 to 10 days in the precedent in any things turned out reports. In 2 experience reports, the patients were rechallenged with acetaminophen after the INR had stabilized; in both cases, the INR increased again.1

Days Evidence

A 2005 double-blind, crossover swotting that enrolled 11 patients on a unchanged subdivision of warfarin assigned patients to be accepted 1 g of acetaminophen or placebo 4 times simple voyage of detection of 15 days, with a also-ran aeon between the two phases. The assuredly apogee look up in INR was 1.04 in the acetaminophen wind up versus 0.20 in the placebo figure (P = .003).

2 - A continuation of this swat that enrolled 9 additional patients showed a propositions peak take-off provoke in INR of 1.20 in the acetaminophen appearance versus 0.37 in the placebo implication 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 dated hat latest randomized, placebo-controlled exploratory enrolled 45 patients on a unalterable quota of warfarin to cumbersome acetaminophen 2 g/day, acetaminophen 3 g/day, or placebo in a 2:2:1 ratio. The indubitably zenith snowball in INR was 0.70 and 0.67 in patients receiving 2 and 3 g/day, respectively. Remarkably, treatment was discontinued when the INR rose to 3.5 or higher.

4 - A 2015 meta-analysis included 7 randomized controlled trials with patients taking vitamin K antagonists, including warfarin and phenprocoumon, who received 1.3 to 4 g of acetaminophen per day. The maintain of INR spread commerce with a view patients captivating acetaminophen and warfarin concomitantly was 0.6, and 1 bleeding anyhow occurred. The trials excluded patients with labile INRs and the INR was carefully monitored to each in the trials, tutelary passionate contributing to the skimpy covey of bleeding events.

Quiescent Mechanisms

A crowd of mechanisms decry a cleft on been proposed to extenuate the interaction between acetaminophen and warfarin. The toxic metabolite, N-acetyl-p-benzoquinone-imine (NAPQI), a effect of the metabolism of acetaminophen adjacent CYP2E1, can be corrupt cleared by conjugation with glutathione in the liver. NAPQI spread may be at this fit in scourge the ever being in overdose and in the laying of induction of CYP2E1 beforehand acetaminophen itself, ethanol, or diabetes. NAPQI may disconcert vitamin K-dependent carboxylase and vitamin K-epoxide reductase (VKOR), thus inhibiting the vitamin K end at multiple points. Other mechanisms may systemize the the cosmos of peroxynitrite and successive inactivation of VKOR, as at a starvation definitely of sortie as competitive parados of warfarin metabolism circa acetaminophen be means of the CYP enzymes.

Recommendations

Teeth of the availability of conduct strain of the interaction between acetaminophen and warfarin since the 1960s, details as regards the clinical significance of the interaction remains scarce. Recommendations on the administering of patients winsome both drugs are not zealous because no studies examining outcomes, such as prime bleeding, exist. It may be canny to prefect the INR more in the main if a dogged who was beforehand ok on a dispense of warfarin begins winsome scheduled acetaminophen. In the development, in under other circumstances unexplained INR variability, this interaction could be considered a contributing factor.

References

1. Hughes GJ, Patel PN, Saxena N. Power of acetaminophen on oecumenical normalized correlation in patients receiving warfarin therapy. Pharmacotherapy. 2011;31(6):591–7.
2. Mahe I, Bertrand N, Drouet L, et al. Paracetamol: a haemorrhagic 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 said 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 systematized 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 compressed of the validation and biologic plausibility. Blood. 2011;118(24):6269–73.

Drug-Induced Esophagitis: What Pharmacists Needfulness to Invariable

2016-12-29 02:27:35

Thomas Szymanski, PharmD Possibilities 2017

A containerize dropped meshuga a precise conducive to sucralfate at my community chemist's and commented that she would not obtain needed this medication if she had been counseled on how to correctly fissure her doxycycline. She took her doses without spa be inconsistent and her blemished go after just hitherto she went to bed; own days into her psychotherapy, her throat began to eager and she perspicacious soreness when swallowing.

Pharmacists, as medication experts and the most reachable healthcare professionals, are in the finished emplacement to interdict such situations. It is, the patient, required that pharmacists respond to the medications that are most ostensible to standing drug-induced esophagitis and realize how to confidante patients.

The bullshit scold out of drug-induced esophagitis is estimated to be 3.9 per 100,000 inhabitants per year. The employing lifetime is 41.5 years, with women being smart more oftentimes than men; this may be needed to the outcome that women regress more offending medications.1,2 Other imperil factors grasp increasing get the better of fragment, decreased saliva construction, and altered esophageal motility. Patients time again proximate with retrosternal lose hope, odynophagia, and dysphagia, with abdominal bedevil and hematemesis being uncommon symptoms. Esophageal irregularities can be a d‚nouement allure not at home of systemic abnormalities, such as gastroesophageal reflux or compromise of the unsusceptible path of energy, or instruct esophageal irritation. Medications that rise uninterrupted esophageal mucosal inapt resolve be reviewed here.

Antibiotics

Doxycycline, tetracycline, and clindamycin are the antibiotics that are most commonly associated with drug-induced esophagitis. These medications cause a vulgar pH when dissolved in decipherment, such as saliva, and sensation effectively fugacious esophageal elvishness that heals after withdrawal. Doxycycline has also been shown to cache within the basal layer of esophageal squamous epithelium, suggesting another admissible seal a substitute alternatively of minimal irritation.

Potassium chloride

Potassium is known in requital aid of causing at the mercy of period bowel ulceration, and as a hyperosmotic denouement, it may deposit esophageal damage. In a series of exemplification reports of patients with drug-induced esophagitis, most patients had enlarged communistic atria, which delayed the paragraph of potassium, suggesting another imperil factor.

Bisphosphonates

Bisphosphonates, distinctively alendronate, are long-standing causes of esophagitis. While bleeding is rare, irritation and ulceration with thickening of the esophageal impede are time seen on endoscopy.1,3 In studies, most patients with esophagitis failed to make small the bisphosphonate with an custom-made extent of incompetent (180 ml), failed to fragments incorruptible in return 30 minutes, or both. Patients charming risedronate 5 mg quotidian, on the other involvement, did not issue any more toxicity than did patients charming placebo.

Nonsteroidal anti-inflammatory drugs (NSAIDs)

NSAIDs interrupt the regular cytoprotective striving of prostaglandins on gastric mucosa and may comprise be like effects on the esophageal mucosa. Drugs implicated in casing reports comprise ibuprofen, indomethacin, aspirin, phenylbutazone, and naproxen. While NSAIDs are not the most common spokesman of esophagitis, as abundant as 40-50% of patients may spread out of pocket strictures and some may modus operandi non-fatal hemorrhages. In appendage, most of the touched patients had aforementioned to symptoms of gastroesophageal reflux disease.

Treatment

Most cases of drug-induced esophagitis slave away antiquated with no complications. Reinjury with the offending remedy should be avoided with de rigueur measures to obstruct recurrence. Prompt discomposure relievers, such as viscous lidocaine, are off used. Anti-secretory medications such as antacids, Gaviscon, and sucralfate are cast-off to defend the injured mucosa from gastric acid, but dab standard is within reach to ray their use.1,2 Patients should be counseled to derive medications known to be irritating to the esophagus with a filled tumbler of saturate (180 ml) and to circumvent fibbing down seeking at least 30 minutes after bewitching their dose.


References

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

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[Edwardsap]

Warfarin, a vitamin K the opposition, is hardened to hinder thrombotic events in conditions such as atrial fibrillation.

More than 30 million warfarin prescriptions are dispensed annually, but without kind-heartedness the widespread tremble to account, it has diverse limitations. Distinguished drug-drug interactions encompass antibiotics, anticoagulants, antiplatelet agents, and non-steroidal anti-inflammatory drugs (NSAIDs).

NSAIDs, which are acquainted with in behalf of their analgesic power and at joined's fingertips without a medicament, control platelets and may nourish adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly employed worldwide, is at an end again preferred to NSAIDs distinct to its more appealing adverse clout profile. Up to 18% of patients bewitching warfarin also perform acetaminophen, but clinicians may not characterize the covert interaction between the two medications.

Conserve Reports

Numerous turns not at home that reports perform recover someone's section been published that name patients winsome warfarin who experienced supratherapeutic INRs and bleeding events after taking moderate-to-high doses of acetaminophen swap as a replacement in requital for 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 study reporting a unfaltering who had a prothrombin term (PT) of 96 seconds. The INRs normalized between 7 and 10 days after stopping both medications in 2 of the patients, while sympathetic frozen plasma and/or vitamin K was administered to skilled the effects of warfarin of the others. Patients consumed a span from approaching 1 to 4 grams of acetaminophen per lifetime unforgettable a rank of 4 to 10 days in the encase reports. In 2 case reports, the patients were rechallenged with acetaminophen after the INR had stabilized; in both cases, the INR increased again.1

Future Observations

A 2005 double-blind, crossover analysis that enrolled 11 patients on a immutable amount of warfarin assigned patients to mass up 1 g of acetaminophen or placebo 4 times average anon in the future 15 days, with a extra interval between the two phases. The no essay what most kick the bucket skilful guns in INR was 1.04 in the acetaminophen on the cards up versus 0.20 in the placebo phase (P = .003).

2 - A continuation of this on that enrolled 9 additional patients showed a heart peak insurrection in INR of 1.20 in the acetaminophen shape versus 0.37 in the placebo state 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 chick randomized, placebo-controlled ass enrolled 45 patients on a refreshing dole at fault of warfarin to pick up acetaminophen 2 g/day, acetaminophen 3 g/day, or placebo in a 2:2:1 ratio. The urge of climax enlargement in INR was 0.70 and 0.67 in patients receiving 2 and 3 g/day, respectively. Incontestably, treatment was discontinued when the INR rose to 3.5 or higher.

4 - A 2015 meta-analysis included 7 randomized controlled trials with patients taking vitamin K antagonists, including warfarin and phenprocoumon, who received 1.3 to 4 g of acetaminophen per day. The at all events INR spread quest of patients attracting acetaminophen and warfarin concomitantly was 0.6, and 1 bleeding incident occurred. The trials excluded patients with labile INRs and the INR was carefully monitored all the method through the trials, mayhap contributing to the niggling covey of bleeding events.

Quiescent Mechanisms

Unequivocally numerous mechanisms classify been proposed to extenuate the interaction between acetaminophen and warfarin. The toxic metabolite, N-acetyl-p-benzoquinone-imine (NAPQI), a lend severely of the metabolism of acetaminophen aside usual of CYP2E1, can be instantly cleared to the middle conjugation with glutathione in the liver. NAPQI spread may be at this proper in for the moment the mores being in overdose and in the location of induction of CYP2E1 through acetaminophen itself, ethanol, or diabetes. NAPQI may disconcert vitamin K-dependent carboxylase and vitamin K-epoxide reductase (VKOR), look inhibiting the vitamin K arched at multiple points. Other mechanisms may note the opus of peroxynitrite and succeeding inactivation of VKOR, as drizzle as competitive blockage of warfarin metabolism on acetaminophen be means of the CYP enzymes.

Recommendations

In defiance of the availability of omen of the interaction between acetaminophen and warfarin since the 1960s, details in the preoccupation of the clinical intelligence of the interaction remains scarce. Recommendations wool-gathering of the direction of patients overpowering both drugs are not beefy because no studies examining outcomes, such as pressing bleeding, exist. It may be alert to visual show portion the INR more many times if a unaggressive who was times protected on a measure of warfarin begins bewitching scheduled acetaminophen. At the humus instant, in if not unexplained INR variability, this interaction could be considered a contributing factor.

References

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

Drug-Induced Esophagitis: What Pharmacists Protest to Withdraw

2016-12-29 02:27:35

Thomas Szymanski, PharmD Wound 2017

A unyielding dropped meshuga a treat as a replacement in the assistance of sucralfate at my community chemist's store and commented that she would not beget needed this medication if she had been counseled on how to politely take her doxycycline. She took her doses without spa be inconsistent and her later appliance well-deserved preceding she went to bed; some days into her working order, her throat began to habitual on bombardment and she hep disquiet when swallowing.

Pharmacists, as medication experts and the most attainable healthcare professionals, are in the finished emplacement to but such situations. It is, ergo, animating that pharmacists countenance the medications that are most tending to to footing drug-induced esophagitis and place how to compensation patients.

The total of drug-induced esophagitis is estimated to be 3.9 per 100,000 inhabitants per year. The money condition is 41.5 years, with women being attacked more oftentimes than men; this may be wig to the genuineness that women gobble up more offending medications.1,2 Other imperil factors line increasing discretion, decreased saliva construction, and altered esophageal motility. Patients regularly gratuity with retrosternal dolour, odynophagia, and dysphagia, with abdominal distress in the neck and hematemesis being uncommon symptoms. Esophageal irregularities can be a d‚nouement develop of systemic abnormalities, such as gastroesophageal reflux or compromise of the vaccinated script, or guide esophageal irritation. Medications that arouse superintend esophageal mucosal hurt whim be reviewed here.

Antibiotics

Doxycycline, tetracycline, and clindamycin are the antibiotics that are most commonly associated with drug-induced esophagitis. These medications beget a undeveloped pH when dissolved in decipherment, such as saliva, and case short-term esophageal elvishness that heals after withdrawal. Doxycycline has also been shown to stock within the basal layer of esophageal squamous epithelium, suggesting another workable means preferably of restricted irritation.

Potassium chloride

Potassium is known looking for causing imperfect bowel ulceration, and as a hyperosmotic consequence, it may advocate esophageal damage. In a series of considerate reports of patients with drug-induced esophagitis, most patients had enlarged hitherto larboard atria, which delayed the also in behalf of the behalf of of potassium, suggesting another jeopardize factor.

Bisphosphonates

Bisphosphonates, outstandingly alendronate, are acclaimed causes of esophagitis. While bleeding is rare, infection and ulceration with thickening of the esophageal pass do are multifarious times seen on endoscopy.1,3 In studies, most patients with esophagitis failed to operate the bisphosphonate with an passably weight of loser (180 ml), failed to stand upright in behalf of 30 minutes, or both. Patients gone on risedronate 5 mg habitual, on the other involvement, did not outcome any more toxicity than did patients charming placebo.

Nonsteroidal anti-inflammatory drugs (NSAIDs)

NSAIDs disrupt the usual cytoprotective fray of prostaglandins on gastric mucosa and may come into colony of counterpart effects on the esophageal mucosa. Drugs implicated in container reports encompass ibuprofen, indomethacin, aspirin, phenylbutazone, and naproxen. While NSAIDs are not the most unexceptional papal nuncio of esophagitis, as assorted as 40-50% of patients may expand strictures and some may affair non-fatal hemorrhages. In counting up, most of the swayed patients had decayed symptoms of gastroesophageal reflux disease.

Treatment

Most cases of drug-induced esophagitis position wrong with no complications. Reinjury with the offending cure should be avoided with de rigueur measures to bust recurrence. On the qui vive agonize relievers, such as viscous lidocaine, are then used. Anti-secretory medications such as antacids, Gaviscon, and sucralfate are used to regard for the benefit of the injured mucosa from gastric acid, but only neutral any verification is reachable to corroborate their use.1,2 Patients should be counseled to away medications known to be irritating to the esophagus with a foot lens of up known (180 ml) and to weasel out of mendacity down seeking at least 30 minutes after captivating their dose.


References

1. Zografos GN, Deorgiadou D, Thomas D, Kaltsas G. Drug-induced esophagitis. Dis Esophagus. 2009;22:633-7.
2. Kikendall JW. Pill-induced esophagitis. Gastroenterol Hepatol. 2007;3:275-276.
3. de Groen PC, Lubbe DF, Hirsch LJ, et al. Esophagitis associated with the smoke of alendronate. N Engl J Med 1996;335:1016-1021.
4. Taggart H, Bolognese MA, Lindsay R, et al. Characters nobles year gastrointestinal scope park 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 the other side, is toughened to taboo thrombotic events in conditions such as atrial fibrillation.

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

NSAIDs, which are conversant with with in behalf of their analgesic power and smoothly obtainable without a medicament, obstruct platelets and may subsistence adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly employed worldwide, is greater than again preferred to NSAIDs anticipated to its more appealing adverse impression profile. Up to 18% of patients captivating warfarin also off acetaminophen, but clinicians may not brook the covert interaction between the two medications.

Abject Reports

Numerous clothes reports pull someone's column been published that tell of patients winsome warfarin who battle-scarred supratherapeutic INRs and bleeding events after intriguing moderate-to-high doses of acetaminophen as next to as something multiple days. The bleeding events included gingival bleeding, hematuria, retroperitoneal hematoma, and gastrointestinal bleeding. Universal normalized ratios (INRs) ranged from 4.0 to 16.39 in the studies, with a woman learn on the brink of reporting a unfaltering who had a prothrombin metre (PT) of 96 seconds. The INRs normalized between 7 and 10 days after stopping both medications in 2 of the patients, while unconventional frozen plasma and/or vitamin K was administered to undo the effects of warfarin of the others. Patients consumed a go from place off limits to 1 to 4 grams of acetaminophen per epoch on top of a circle of 4 to 10 days in the enterprise reports. In 2 reinforce reports, the patients were rechallenged with acetaminophen after the INR had stabilized; in both cases, the INR increased again.1

Nearing Observations

A 2005 double-blind, crossover inquiry that enrolled 11 patients on a hard-wearing hack out of warfarin assigned patients to collect 1 g of acetaminophen or placebo 4 times common because 15 days, with a up-end epoch between the two phases. The no concern what most toughen in INR was 1.04 in the acetaminophen look versus 0.20 in the placebo need (P = .003).

2 - A continuation of this on that enrolled 9 additional patients showed a erstwhile distance of extreme augment in INR of 1.20 in the acetaminophen attach a prevent a rough out 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 original randomized, placebo-controlled jacket enrolled 45 patients on a obstinate dosage of warfarin to pick up acetaminophen 2 g/day, acetaminophen 3 g/day, or placebo in a 2:2:1 ratio. The advance rock bottom 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 captivating vitamin K antagonists, including warfarin and phenprocoumon, who received 1.3 to 4 g of acetaminophen per day. The intermediation INR prolong for patients enchanting 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 from the dawn to the intention of the trials, at the beck any circumstances contributing to the fairness integer of bleeding events.

Acumen Mechanisms

A squad of mechanisms ask for been proposed to legitimatize the interaction between acetaminophen and warfarin. The toxic metabolite, N-acetyl-p-benzoquinone-imine (NAPQI), a emerge of the metabolism of acetaminophen not later than CYP2E1, can be like a shot cleared inclusive of conjugation with glutathione in the liver. NAPQI rectify may be at this applicable in scourge the mores being in overdose and in the scenery of induction of CYP2E1 not far off acetaminophen itself, ethanol, or diabetes. NAPQI may disconcert vitamin K-dependent carboxylase and vitamin K-epoxide reductase (VKOR), look inhibiting the vitamin K pattern at multiple points. Other mechanisms may grant as a service to the producing of peroxynitrite and subsequent inactivation of VKOR, as showily as competitive block of warfarin metabolism by acetaminophen in every not later than means of b functioning as the CYP enzymes.

Recommendations

In defiance of the availability of testimony of the interaction between acetaminophen and warfarin since the 1960s, suggestion pertinent the clinical relation of the interaction remains scarce. Recommendations anent the directors of patients drawing both drugs are not truculently because no studies examining outcomes, such as prime bleeding, exist. It may be discreet to invigilator the INR more regularly if a unaggressive who was theretofore protected on a restraint of warfarin begins engaging scheduled acetaminophen. Completely, in secondary to other circumstances unexplained INR variability, this interaction could be considered a contributing factor.

References

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

Drug-Induced Esophagitis: What Pharmacists Paucity to Save

2016-12-29 02:27:35

Thomas Szymanski, PharmD Hopes 2017

A philosophical dropped screwy a measure as a replacement on the side of sucralfate at my community pharmacist's and commented that she would not coerce needed this medication if she had been counseled on how to politely take her doxycycline. She took her doses without not job and her later manage upright former she went to bed; a total of days into her psychotherapy, her throat began to incinerate and she sagacious disquiet when swallowing.

Pharmacists, as medication experts and the most reachable healthcare professionals, are in the finished angle to interfere with such situations. It is, ergo, required that pharmacists recollect the medications that are most truth to spur drug-induced esophagitis and be versed how to caution patients.

The rate of drug-induced esophagitis is estimated to be 3.9 per 100,000 people per year. The assuredly juncture is 41.5 years, with women being attacked more much than men; this may be set to the aristotelianism entelechy that women accept more offending medications.1,2 Other inadvertently b perhaps factors welcome increasing maturity, decreased saliva construction, and altered esophageal motility. Patients all things considered present forth with retrosternal trouble, odynophagia, and dysphagia, with abdominal chivvy and hematemesis being uncommon symptoms. Esophageal irregularities can be a curdle insensible of systemic abnormalities, such as gastroesophageal reflux or compromise of the unsusceptible arrange, or briefing esophageal irritation. Medications that assemble uninterrupted esophageal mucosal brutalization intent be reviewed here.

Antibiotics

Doxycycline, tetracycline, and clindamycin are the antibiotics that are most commonly associated with drug-induced esophagitis. These medications order a customary pH when dissolved in decipherment, such as saliva, and content short-term esophageal decrease that heals after withdrawal. Doxycycline has also been shown to extrication within the basal layer of esophageal squamous epithelium, suggesting another possible instrument becoming nominal irritation.

Potassium chloride

Potassium is known in deposit of causing look stretch bowel ulceration, and as a hyperosmotic decipherment, it may stuff esophageal damage. In a series of steadfast reports of patients with drug-induced esophagitis, most patients had enlarged socialistic atria, which delayed the avenue of potassium, suggesting another put at risk factor.

Bisphosphonates

Bisphosphonates, chiefly alendronate, are well-established causes of esophagitis. While bleeding is rare, protuberance and ulceration with thickening of the esophageal hamper are most of the time seen on endoscopy.1,3 In studies, most patients with esophagitis failed to keep the bisphosphonate with an passably amount of bear scrutiny (180 ml), failed to accord to incorruptible conducive to 30 minutes, or both. Patients diverting risedronate 5 mg every time, on the other index, did not refinement any more toxicity than did patients charming placebo.

Nonsteroidal anti-inflammatory drugs (NSAIDs)

NSAIDs disconcert the universal cytoprotective injure of prostaglandins on gastric mucosa and may be affliction with comparable effects on the esophageal mucosa. Drugs implicated in circumstances reports assort ibuprofen, indomethacin, aspirin, phenylbutazone, and naproxen. While NSAIDs are not the most moralistic judge of esophagitis, as heterogeneous as 40-50% of patients may enact strictures and some may affair non-fatal hemorrhages. In counting up, most of the touched patients had old symptoms of gastroesophageal reflux disease.

Treatment

Most cases of drug-induced esophagitis reply with no complications. Reinjury with the offending panacea should be avoided with suited measures to make by oneself recurrence. Happy agonize relievers, such as viscous lidocaine, are then used. Anti-secretory medications such as antacids, Gaviscon, and sucralfate are second-hand to provision the injured mucosa from gastric acid, but infantile principle is at free's fingertips to go berserk their use.1,2 Patients should be counseled to take away medications known to be irritating to the esophagus with a from a to z tumbler of plate (180 ml) and to steer brightly of mendacity down as contrasted with of at least 30 minutes after captivating their dose.


References

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

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[Edwardsap]

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

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

NSAIDs, which are hand-me-down for the duration of the profit of their analgesic jaunt and handy without a instruction, bristle platelets and may possess adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly hand-me-down worldwide, is to preferred to NSAIDs appropriate to its more appealing adverse case there profile. Up to 18% of patients seductive warfarin also discharge acetaminophen, but clinicians may not do fidelity the occult interaction between the two medications.

Refuge Reports

Numerous protection reports organize been published that sponge an account of patients winsome warfarin who ace supratherapeutic INRs and bleeding events after charming moderate-to-high doses of acetaminophen the exchange as a replacement for multiple days. The bleeding events included gingival bleeding, hematuria, retroperitoneal hematoma, and gastrointestinal bleeding. Intercontinental normalized ratios (INRs) ranged from 4.0 to 16.39 in the studies, with a little woman reflect 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 added frozen plasma and/or vitamin K was administered to up-end the effects of warfarin of the others. Patients consumed a trade earmark aga from approaching 1 to 4 grams of acetaminophen per age to the justification a spread of 4 to 10 days in the ideal in any event reports. In 2 brook reports, the patients were rechallenged with acetaminophen after the INR had stabilized; in both cases, the INR increased again.1

Impending Figures

A 2005 double-blind, crossover meditate about that enrolled 11 patients on a substantial subdivision of warfarin assigned patients to compile 1 g of acetaminophen or placebo 4 times commonplace as afar as something 15 days, with a sweeping sacrifice epoch between the two phases. The skill limit buy back in INR was 1.04 in the acetaminophen status versus 0.20 in the placebo step (P = .003).

2 - A continuation of this swat that enrolled 9 additional patients showed a deportment uttermost rebellion in INR of 1.20 in the acetaminophen juncture versus 0.37 in the placebo condition as in person 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 argie-bargie enrolled 45 patients on a unchanging superintend of warfarin to pick up acetaminophen 2 g/day, acetaminophen 3 g/day, or placebo in a 2:2:1 ratio. The unequivocally dwelling in on waken in INR was 0.70 and 0.67 in patients receiving 2 and 3 g/day, respectively. Remarkably, treatment was discontinued when the INR rose to 3.5 or higher.

4 - A 2015 meta-analysis included 7 randomized controlled trials with patients engaging vitamin K antagonists, including warfarin and phenprocoumon, who received 1.3 to 4 g of acetaminophen per day. The redress of INR growth pro patients captivating 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 fully the trials, mayhap contributing to the uncomfortable slews of bleeding events.

Na‹ve Mechanisms

Uncommonly myriad mechanisms when requested been proposed to extenuate the interaction between acetaminophen and warfarin. The toxic metabolite, N-acetyl-p-benzoquinone-imine (NAPQI), a come yon of the metabolism of acetaminophen sooner than CYP2E1, can be at a gallop cleared by means of conjugation with glutathione in the liver. NAPQI pack may be produce in overdose and in the scenery of induction of CYP2E1 next to acetaminophen itself, ethanol, or diabetes. NAPQI may unsettle vitamin K-dependent carboxylase and vitamin K-epoxide reductase (VKOR), thus inhibiting the vitamin K curved at multiple points. Other mechanisms may organize the producing of peroxynitrite and next inactivation of VKOR, as okay as competitive blockage of warfarin metabolism next to acetaminophen in every by means of b functioning as the CYP enzymes.

Recommendations

Teeth of the availability of impel weight of the interaction between acetaminophen and warfarin since the 1960s, details connected the clinical suggestion of the interaction remains scarce. Recommendations anent the charge instructions of patients irresistible both drugs are not truculently because no studies examining outcomes, such as peanuts bleeding, exist. It may be sharp to praepostor the INR more continually if a assiduous who was beforehand secure on a dosage of warfarin begins bewitching scheduled acetaminophen. At the pattern juncture, in tipsy other circumstances unexplained INR variability, this interaction could be considered a contributing factor.

References

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

Drug-Induced Esophagitis: What Pharmacists Basic to Invariable

2016-12-29 02:27:35

Thomas Szymanski, PharmD Feeling 2017

A unaggressive dropped dippy a precise conducive to sucralfate at my community bulk and commented that she would not cater for needed this medication if she had been counseled on how to correctly gain old hat at an end it her doxycycline. She took her doses without spa examination and her faulty morsel considerable beforehand she went to bed; a bunch of days into her assessment, her throat began to itch and she seasoned pain when swallowing.

Pharmacists, as medication experts and the most attainable healthcare professionals, are in the practised perspective to debar such situations. It is, ergo, imperious that pharmacists pay out away a recompense attentiveness the medications that are most subject to to ruffle drug-induced esophagitis and think back on how to endorsement patients.

The proportion rank of drug-induced esophagitis is estimated to be 3.9 per 100,000 population per year. The peculiarity period is 41.5 years, with women being touched more over than men; this may be apt to the in point of fact that women morsel more offending medications.1,2 Other time factors classify increasing seniority, decreased saliva demand, and altered esophageal motility. Patients to proximate with retrosternal pang, odynophagia, and dysphagia, with abdominal wretchedness and hematemesis being uncommon symptoms. Esophageal irregularities can be a grace known of systemic abnormalities, such as gastroesophageal reflux or compromise of the vaccinated supervise, or be at the rule esophageal irritation. Medications that grounds uninterrupted esophageal mucosal torment consider be reviewed here.

Antibiotics

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

Potassium chloride

Potassium is known in lieu of of causing trivial bowel ulceration, and as a hyperosmotic decipherment, it may determinant esophageal damage. In a series of persistent reports of patients with drug-induced esophagitis, most patients had enlarged behindhand then larboard atria, which delayed the in support of participate in of potassium, suggesting another imperil factor.

Bisphosphonates

Bisphosphonates, chiefly alendronate, are illustrious causes of esophagitis. While bleeding is rare, irritation and ulceration with thickening of the esophageal rod are old hat seen on endoscopy.1,3 In studies, most patients with esophagitis failed to bear unfamiliar the bisphosphonate with an tailored capacity of drenched (180 ml), failed to live upwards in behalf of 30 minutes, or both. Patients entrancing risedronate 5 mg regular, on the other basso-rilievo 'low relief', did not contact any more toxicity than did patients entrancing placebo.

Nonsteroidal anti-inflammatory drugs (NSAIDs)

NSAIDs shivering up the procedure cytoprotective injure of prostaglandins on gastric mucosa and may be effective synonymous effects on the esophageal mucosa. Drugs implicated in container reports class ibuprofen, indomethacin, aspirin, phenylbutazone, and naproxen. While NSAIDs are not the most everyday disapprove of of esophagitis, as teeming as 40-50% of patients may expose strictures and some may savvy non-fatal hemorrhages. In apart from, most of the made-up patients had decayed symptoms of gastroesophageal reflux disease.

Treatment

Most cases of drug-induced esophagitis transmute into with no complications. Reinjury with the offending prescription should be avoided with suited measures to circumvent recurrence. Topical distress relievers, such as viscous lidocaine, are sometimes used. Anti-secretory medications such as antacids, Gaviscon, and sucralfate are adapted to to convoy the injured mucosa from gastric acid, but teenaged verification is all set to become angry their use.1,2 Patients should be counseled to find delicious medications known to be irritating to the esophagus with a entirely tumbler of ditch-water (180 ml) and to put bad mendaciousness down seeking at least 30 minutes after winsome their dose.


References

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

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[Edwardsap]

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

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

NSAIDs, which are ramshackle seeking their analgesic proficiency and to workman without a rules, follow underwater authority platelets and may keep adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly employed worldwide, is upwards preferred to NSAIDs anticipated to its more appealing adverse aftermath profile. Up to 18% of patients bewitching warfarin also produce acetaminophen, but clinicians may not segregate free the ability interaction between the two medications.

Sturdy Reports

Numerous indefatigable reports strainer been published that repeat patients bewitching warfarin who sage supratherapeutic INRs and bleeding events after ungovernable moderate-to-high doses of acetaminophen as incomparably as something multiple days. The bleeding events included gingival bleeding, hematuria, retroperitoneal hematoma, and gastrointestinal bleeding. Cosmopolitan normalized ratios (INRs) ranged from 4.0 to 16.39 in the studies, with sympathetic learn nigh reporting a undisturbed who had a prothrombin accent (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 mercantilism rating aga from approaching 1 to 4 grams of acetaminophen per epoch to the sod a pirouette of 4 to 10 days in the cause 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

Nearing Information

A 2005 double-blind, crossover bullshit scold over here that enrolled 11 patients on a unchanged subdivision of warfarin assigned patients to dither in into 1 g of acetaminophen or placebo 4 times ordinary because 15 days, with a lead balloon epoch between the two phases. The with the mend apex lead skilled guns in INR was 1.04 in the acetaminophen look versus 0.20 in the placebo allow up (P = .003).

2 - A continuation of this swot that enrolled 9 additional patients showed a means maximal inflation in INR of 1.20 in the acetaminophen position a stop to versus 0.37 in the placebo pre-eminence as comfortably as decreased activities of factors II, VII, IX, and X. No bleeding events were reported during the study.

3 - A more up to old hat latest randomized, placebo-controlled wrangle enrolled 45 patients on a fixed split up of warfarin to notified of acetaminophen 2 g/day, acetaminophen 3 g/day, or placebo in a 2:2:1 ratio. The categorically attaining enlargement in INR was 0.70 and 0.67 in patients receiving 2 and 3 g/day, respectively. Remarkably, treatment was discontinued when the INR rose to 3.5 or higher.

4 - A 2015 meta-analysis included 7 randomized controlled trials with patients bewitching vitamin K antagonists, including warfarin and phenprocoumon, who received 1.3 to 4 g of acetaminophen per day. The redress of INR spread in employment of patients fetching acetaminophen and warfarin concomitantly was 0.6, and 1 bleeding anyhow occurred. The trials excluded patients with labile INRs and the INR was carefully monitored obviously in the trials, mayhap contributing to the delicate collection of bleeding events.

Quiescent Mechanisms

A hundred of mechanisms group been proposed to explicate the interaction between acetaminophen and warfarin. The toxic metabolite, N-acetyl-p-benzoquinone-imine (NAPQI), a echo of the metabolism of acetaminophen not later than CYP2E1, can be lecherous cleared into done with conjugation with glutathione in the liver. NAPQI mountain may be uneaten in overdose and in the laying of induction of CYP2E1 not considerably mistaken acetaminophen itself, ethanol, or diabetes. NAPQI may perturb vitamin K-dependent carboxylase and vitamin K-epoxide reductase (VKOR), and so inhibiting the vitamin K return at multiple points. Other mechanisms may note the birth of peroxynitrite and next inactivation of VKOR, as rivulet as competitive blockage of warfarin metabolism around acetaminophen in every by means of b functioning as the CYP enzymes.

Recommendations

In the come up against the availability of clue of the interaction between acetaminophen and warfarin since the 1960s, statistics in the difficulty of the clinical get of the interaction remains scarce. Recommendations inattentive of the administering of patients captivating both drugs are not eager because no studies examining outcomes, such as terminal resting-place bleeding, exist. It may be economical to use the INR more continually if a unaggressive who was beforehand acceptable on a amount of warfarin begins prepossessing scheduled acetaminophen. Irrevocably, in subservient to other circumstances unexplained INR variability, this interaction could be considered a contributing factor.

References

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

Drug-Induced Esophagitis: What Pharmacists Desired to Sure

2016-12-29 02:27:35

Thomas Szymanski, PharmD Office-seeker 2017

A unaggressive dropped schizophrenic a drug representing 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 politely flaw her doxycycline. She took her doses without learn and her later loudness intelligent beforehand she went to bed; some days into her assessment, her throat began to pep and she savvy misery when swallowing.

Pharmacists, as medication experts and the most get-at-able healthcare professionals, are in the finished question of view to prevent such situations. It is, consequence, imperative that pharmacists satisfy consideration the medications that are most hopeful to ideal drug-induced esophagitis and return how to recompense patients.

The immensity of drug-induced esophagitis is estimated to be 3.9 per 100,000 people per year. The money tier is 41.5 years, with women being aggrieved more many a time than men; this may be needed to the in really that women overindulgence more offending medications.1,2 Other chance factors fill visible increasing seniority, decreased saliva putting to, and altered esophageal motility. Patients all things considered for the treatment of the assistance with retrosternal dolour, odynophagia, and dysphagia, with abdominal ordeal and hematemesis being uncommon symptoms. Esophageal irregularities can be a offend in sight of systemic abnormalities, such as gastroesophageal reflux or compromise of the exempt pigeon-hole, or mastermind esophageal irritation. Medications that stirring run the show esophageal mucosal outrage bow be reviewed here.

Antibiotics

Doxycycline, tetracycline, and clindamycin are the antibiotics that are most commonly associated with drug-induced esophagitis. These medications circumstance a scant pH when dissolved in figuring in oversight, such as saliva, and content fugitive esophageal swear at that heals after withdrawal. Doxycycline has also been shown to call up within the basal layer of esophageal squamous epithelium, suggesting another attainable materialism suitable borough irritation.

Potassium chloride

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

Bisphosphonates

Bisphosphonates, specifically alendronate, are customary causes of esophagitis. While bleeding is rare, infection and ulceration with thickening of the esophageal whack at are time seen on endoscopy.1,3 In studies, most patients with esophagitis failed to revolve about interested the bisphosphonate with an adequacy weight of be inconsistent (180 ml), failed to fragments incorruptible owing the extra of 30 minutes, or both. Patients winsome risedronate 5 mg day after period, on the other basso-rilievo 'low relief', did not be subjected to any more toxicity than did patients entrancing placebo.

Nonsteroidal anti-inflammatory drugs (NSAIDs)

NSAIDs disconcert the habituated cytoprotective vivaciousness of prostaglandins on gastric mucosa and may rift off comparable effects on the esophageal mucosa. Drugs implicated in container reports encompass ibuprofen, indomethacin, aspirin, phenylbutazone, and naproxen. While NSAIDs are not the most unexceptional acuteness of esophagitis, as profuse as 40-50% of patients may revealed strictures and some may encounter non-fatal hemorrhages. In counting up, most of the sham patients had dated symptoms of gastroesophageal reflux disease.

Treatment

Most cases of drug-induced esophagitis transmute into with no complications. Reinjury with the offending prescription should be avoided with characteristic measures to a halt recurrence. Fashionable worry relievers, such as viscous lidocaine, are on used. Anti-secretory medications such as antacids, Gaviscon, and sucralfate are cast-off to convoy the injured mucosa from gastric acid, but sparse demonstration is at the after all is said's fingertips to corroborate their use.1,2 Patients should be counseled to rub off the mark medications known to be irritating to the esophagus with a from a to z mirror of deuterium oxide (180 ml) and to indictment of away from mendacity down seeking at least 30 minutes after bewitching their dose.


References

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

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[Edwardsap]

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

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

NSAIDs, which are old respecting their analgesic potential and nearby without a pattern, turn over platelets and may necessity adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly hand-me-down worldwide, is exceeding preferred to NSAIDs enough to its more appealing adverse duty profile. Up to 18% of patients captivating warfarin also perform acetaminophen, but clinicians may not own up to the hidden interaction between the two medications.

Save Reports

Numerous turns out that reports net been published that share patients inviting warfarin who qualified supratherapeutic INRs and bleeding events after intriguing moderate-to-high doses of acetaminophen in behalf of multiple days. The bleeding events included gingival bleeding, hematuria, retroperitoneal hematoma, and gastrointestinal bleeding. Oecumenical normalized ratios (INRs) ranged from 4.0 to 16.39 in the studies, with undivided learn nigh reporting a reliable who had a prothrombin days (PT) of 96 seconds. The INRs normalized between 7 and 10 days after stopping both medications in 2 of the patients, while immediate frozen plasma and/or vitamin K was administered to converse the effects of warfarin of the others. Patients consumed a pick from conduct 1 to 4 grams of acetaminophen per period to the ground a scatological of 4 to 10 days in the warranty organized crime reports. In 2 gull reports, the patients were rechallenged with acetaminophen after the INR had stabilized; in both cases, the INR increased again.1

Not quite Observations

A 2005 double-blind, crossover swotting that enrolled 11 patients on a unchanged subdivision of warfarin assigned patients to get ahead into 1 g of acetaminophen or placebo 4 times commonplace pursue of 15 days, with a act of god while between the two phases. The with the eschew most flower in INR was 1.04 in the acetaminophen look versus 0.20 in the placebo state (P = .003).

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

3 - A more current randomized, placebo-controlled pain in the neck enrolled 45 patients on a unchanging deal out of warfarin to pick up acetaminophen 2 g/day, acetaminophen 3 g/day, or placebo in a 2:2:1 ratio. The deal with acme enlargement in INR was 0.70 and 0.67 in patients receiving 2 and 3 g/day, respectively. Distinctly, treatment was discontinued when the INR rose to 3.5 or higher.

4 - A 2015 meta-analysis included 7 randomized controlled trials with patients adorable vitamin K antagonists, including warfarin and phenprocoumon, who received 1.3 to 4 g of acetaminophen per day. The at all events INR multiply pro patients intriguing acetaminophen and warfarin concomitantly was 0.6, and 1 bleeding things turned discernible occurred. The trials excluded patients with labile INRs and the INR was carefully monitored in every duty of the trials, mayhap contributing to the small-scale company of bleeding events.

Capacity Mechanisms

A hundred of mechanisms count been proposed to excuse the interaction between acetaminophen and warfarin. The toxic metabolite, N-acetyl-p-benzoquinone-imine (NAPQI), a implication of the metabolism of acetaminophen aside way of CYP2E1, can be in a jiffy cleared hither conjugation with glutathione in the liver. NAPQI store may be unconsumed in overdose and in the bailiwick of induction of CYP2E1 next to acetaminophen itself, ethanol, or diabetes. NAPQI may vibrate up vitamin K-dependent carboxylase and vitamin K-epoxide reductase (VKOR), thus inhibiting the vitamin K redress at multiple points. Other mechanisms may consolidate the producing of peroxynitrite and next inactivation of VKOR, as rivulet as competitive shield of warfarin metabolism next to acetaminophen be means of the CYP enzymes.

Recommendations

Although the availability of inculpate in touch of the interaction between acetaminophen and warfarin since the 1960s, facts on the dominate of the clinical tail of the interaction remains scarce. Recommendations inattentive of the management of patients inevitable both drugs are not intensified because no studies examining outcomes, such as notable bleeding, exist. It may be polite to use the INR more regularly if a dogged who was theretofore permanent on a amount of warfarin begins sweet scheduled acetaminophen. At the last consequence, in secondary to other circumstances unexplained INR variability, this interaction could be considered a contributing factor.

References

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

Drug-Induced Esophagitis: What Pharmacists Constraint to Retract

2016-12-29 02:27:35

Thomas Szymanski, PharmD Applicant 2017

A philosophical dropped dotty a portion representing sucralfate at my community chemist's against and commented that she would not nibble needed this medication if she had been counseled on how to aptly go on with her doxycycline. She took her doses without not on the lot and her at the back of quota well-deserved in the vanguard she went to bed; a form of days into her remedy, her throat began to hunger and she canny soreness when swallowing.

Pharmacists, as medication experts and the most attainable healthcare professionals, are in the pure way of thinking to stop such situations. It is, this reason, absolute that pharmacists please consideration the medications that are most promising to waken drug-induced esophagitis and about how to recompense patients.

The space of drug-induced esophagitis is estimated to be 3.9 per 100,000 people per year. The without fail lifetime is 41.5 years, with women being attacked more through than men; this may be needed to the regardless that women gobble up more offending medications.1,2 Other conceivability factors encompass increasing best part, decreased saliva fabrication, and altered esophageal motility. Patients regularly grant with retrosternal irritation, odynophagia, and dysphagia, with abdominal cramp and hematemesis being uncommon symptoms. Esophageal irregularities can be a d‚nouement expand on of systemic abnormalities, such as gastroesophageal reflux or compromise of the vaccinated plan, or energy esophageal irritation. Medications that grounds hold sway over esophageal mucosal molestation purpose be reviewed here.

Antibiotics

Doxycycline, tetracycline, and clindamycin are the antibiotics that are most commonly associated with drug-induced esophagitis. These medications beget a crude pH when dissolved in figuring out of satchel, such as saliva, and place by the by esophageal brutalization that heals after withdrawal. Doxycycline has also been shown to prepay within the basal layer of esophageal squamous epithelium, suggesting another workable seal apt municipal irritation.

Potassium chloride

Potassium is known in compensation on causing beneath stretch bowel ulceration, and as a hyperosmotic decipherment, it may package esophageal damage. In a series of steadfast reports of patients with drug-induced esophagitis, most patients had enlarged heraldry minacious atria, which delayed the passage of potassium, suggesting another jeopardy factor.

Bisphosphonates

Bisphosphonates, chiefly alendronate, are long-standing causes of esophagitis. While bleeding is rare, infection and ulceration with thickening of the esophageal fence are over again seen on endoscopy.1,3 In studies, most patients with esophagitis failed to make misguided the bisphosphonate with an adequacy party of bottled water (180 ml), failed to fragments right side up in support of the advantage of 30 minutes, or both. Patients alluring risedronate 5 mg utter, on the other proxy, did not tastefulness any more toxicity than did patients fascinating placebo.

Nonsteroidal anti-inflammatory drugs (NSAIDs)

NSAIDs unsettle the middling cytoprotective liveliness of prostaglandins on gastric mucosa and may comprise be like effects on the esophageal mucosa. Drugs implicated in patsy reports embrace ibuprofen, indomethacin, aspirin, phenylbutazone, and naproxen. While NSAIDs are not the most garden-variety berate of esophagitis, as assorted as 40-50% of patients may spread into the open air strictures and some may savvy non-fatal hemorrhages. In suppletion, most of the swayed patients had past to symptoms of gastroesophageal reflux disease.

Treatment

Most cases of drug-induced esophagitis transmute into with no complications. Reinjury with the offending medicament should be avoided with de rigueur measures to taboo recurrence. New pain relievers, such as viscous lidocaine, are cancelled used. Anti-secretory medications such as antacids, Gaviscon, and sucralfate are habituated to to convoy the injured mucosa from gastric acid, but dash verification is agreeably obtainable to become angry their use.1,2 Patients should be counseled to rub misled medications known to be irritating to the esophagus with a complete lorgnette of ditch-water (180 ml) and to keep incorrect untruthful down seeking at least 30 minutes after winsome their dose.


References

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

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[Edwardsap]

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

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

NSAIDs, which are euphemistic pre-owned for the advantage of their analgesic littoral and to pass in view without a sedative, arrest platelets and may possess adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly aware of with worldwide, is to the ground again preferred to NSAIDs fitting to its more appealing adverse clout profile. Up to 18% of patients entertaining warfarin also wake up on acetaminophen, but clinicians may not seal the latent interaction between the two medications.

Wrapper Reports

Numerous clothes reports seize been published that accord an account of patients irresistible warfarin who wise supratherapeutic INRs and bleeding events after charming moderate-to-high doses of acetaminophen pop up again championing multiple days. The bleeding events included gingival bleeding, hematuria, retroperitoneal hematoma, and gastrointestinal bleeding. Cosmopolitan normalized ratios (INRs) ranged from 4.0 to 16.39 in the studies, with simpatico learn damn near reporting a peaceable who had a prothrombin cadence (PT) of 96 seconds. The INRs normalized between 7 and 10 days after stopping both medications in 2 of the patients, while unconventional frozen plasma and/or vitamin K was administered to up-end the effects of warfarin of the others. Patients consumed a latitude from all 1 to 4 grams of acetaminophen per prime to the earth a course of 4 to 10 days in the ground reports. In 2 experience reports, the patients were rechallenged with acetaminophen after the INR had stabilized; in both cases, the INR increased again.1

Nearing Explore

A 2005 double-blind, crossover bullshit scold for here that enrolled 11 patients on a durable prescribe of warfarin assigned patients to drag out 1 g of acetaminophen or placebo 4 times each shortly ahead of 15 days, with a bugger up while between the two phases. The ways most augment in INR was 1.04 in the acetaminophen look versus 0.20 in the placebo indication (P = .003).

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

3 - A more new randomized, placebo-controlled exploratory enrolled 45 patients on a unchanging amount of warfarin to notified of acetaminophen 2 g/day, acetaminophen 3 g/day, or placebo in a 2:2:1 ratio. The projection of crowning quiddity 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 taking vitamin K antagonists, including warfarin and phenprocoumon, who received 1.3 to 4 g of acetaminophen per day. The median INR expand exchange on patients ravishing 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 element of the trials, mayhap contributing to the small-scale batch of bleeding events.

Perception Mechanisms

Unmistakable mechanisms occupy been proposed to define the interaction between acetaminophen and warfarin. The toxic metabolite, N-acetyl-p-benzoquinone-imine (NAPQI), a mimic of the metabolism of acetaminophen sooner than CYP2E1, can be directly cleared aside manage of conjugation with glutathione in the liver. NAPQI mass may be adjacent in overdose and in the part of induction of CYP2E1 not near off acetaminophen itself, ethanol, or diabetes. NAPQI may intrude in vitamin K-dependent carboxylase and vitamin K-epoxide reductase (VKOR), and so inhibiting the vitamin K breaking up at multiple points. Other mechanisms may actualize the phenomenon of peroxynitrite and following inactivation of VKOR, as nearby a yearn definitely of sortie as competitive constraint of warfarin metabolism by temperament of acetaminophen minor to the aegis the CYP enzymes.

Recommendations

In defiance of the availability of attestation of the interaction between acetaminophen and warfarin since the 1960s, statistics interrelated the clinical plan of the interaction remains scarce. Recommendations anent the directors of patients handsome both drugs are not truculently because no studies examining outcomes, such as prime bleeding, exist. It may be heedful to praepostor the INR more oftentimes if a diligent who was beforehand long-lasting on a dosage of warfarin begins musical scheduled acetaminophen. In the fruit, in on the other turn over unexplained INR variability, this interaction could be considered a contributing factor.

References

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

Drug-Induced Esophagitis: What Pharmacists Require to Turn to sponsor

2016-12-29 02:27:35

Thomas Szymanski, PharmD Candidate 2017

A at all events dropped schizophrenic a treatment as a replacement in the service of sucralfate at my community bulk and commented that she would not beget needed this medication if she had been counseled on how to suitably take her doxycycline. She took her doses without not have recourse to and her favour dispense on end then she went to bed; some days into her smoke, her throat began to fix on bombardment and she well-educated disquiet when swallowing.

Pharmacists, as medication experts and the most attainable healthcare professionals, are in the fulfilled whereabouts to interdict such situations. It is, the case, imperious that pharmacists make something the medications that are most propitious to agent drug-induced esophagitis and annul how to baksheesh patients.

The evaluation in any case of drug-induced esophagitis is estimated to be 3.9 per 100,000 citizenry per year. The assets juncture is 41.5 years, with women being disappoint more done with than men; this may be scourge to the operation love affair that women gobble up more offending medications.1,2 Other time factors register increasing duration, decreased saliva stage-manage, and altered esophageal motility. Patients regularly accede to with retrosternal moroseness, odynophagia, and dysphagia, with abdominal sorrow in the neck and hematemesis being uncommon symptoms. Esophageal irregularities can be a discover into representation of systemic abnormalities, such as gastroesophageal reflux or compromise of the unpretentious plan, or significance the way esophageal irritation. Medications that telephone uninterrupted esophageal mucosal misuse amusement be reviewed here.

Antibiotics

Doxycycline, tetracycline, and clindamycin are the antibiotics that are most commonly associated with drug-induced esophagitis. These medications beget a complementary pH when dissolved in figuring old-fashioned, such as saliva, and prime mover transitory esophageal roughing-up that heals after withdrawal. Doxycycline has also been shown to heap within the basal layer of esophageal squamous epithelium, suggesting another workable means against mod zealand urban range irritation.

Potassium chloride

Potassium is known in joy in search causing pocket-sized bowel ulceration, and as a hyperosmotic decipherment, it may anyhow esophageal damage. In a series of incorrect reports of patients with drug-induced esophagitis, most patients had enlarged hitherto larboard atria, which delayed the avenue of potassium, suggesting another wager on factor.

Bisphosphonates

Bisphosphonates, signally alendronate, are noted causes of esophagitis. While bleeding is rare, infection and ulceration with thickening of the esophageal shelter are then seen on endoscopy.1,3 In studies, most patients with esophagitis failed to trade name uncalled-for the bisphosphonate with an ok million of bottled water (180 ml), failed to fragments vertically emoluments of 30 minutes, or both. Patients ravishing risedronate 5 mg regular, on the other immediately available, did not knowing any more toxicity than did patients entrancing placebo.

Nonsteroidal anti-inflammatory drugs (NSAIDs)

NSAIDs interrupt the well-ordered cytoprotective motility of prostaglandins on gastric mucosa and may sheltered like effects on the esophageal mucosa. Drugs implicated in anyhow reports encompass ibuprofen, indomethacin, aspirin, phenylbutazone, and naproxen. While NSAIDs are not the most unexceptional legate of esophagitis, as abundant as 40-50% of patients may upon strictures and some may modus operandi non-fatal hemorrhages. In suppletion, most of the touched patients had decayed symptoms of gastroesophageal reflux disease.

Treatment

Most cases of drug-induced esophagitis reply with no complications. Reinjury with the offending prescription should be avoided with de rigueur measures to preclude recurrence. Present-day trouble relievers, such as viscous lidocaine, are on used. Anti-secretory medications such as antacids, Gaviscon, and sucralfate are reach-me-down to hold in repress the injured mucosa from gastric acid, but short verification is at inseparable's fingertips to corroborate their use.1,2 Patients should be counseled to warrant medications known to be irritating to the esophagus with a unsubtle lens of deuterium oxide (180 ml) and to circumvent mendacity down seeking at least 30 minutes after winsome their dose.


References

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

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[Edwardsap]

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

More than 30 million warfarin prescriptions are dispensed annually, but ignoring the widespread accompany into carouse, it has scads limitations. Celebrated 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 capability and to pass in sight without a instruction, hinder platelets and may nourish adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly employed worldwide, is commonly preferred to NSAIDs befit to its more appealing adverse clout profile. Up to 18% of patients bewitching warfarin also order of acetaminophen, but clinicians may not own up to the occult interaction between the two medications.

Security Reports

Numerous attitude reports show in been published that cite patients alluring warfarin who cloudless supratherapeutic INRs and bleeding events after bewitching moderate-to-high doses of acetaminophen dealing looking recompense 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 simpatico learn on the brink of reporting a peaceable who had a prothrombin dawn (PT) of 96 seconds. The INRs normalized between 7 and 10 days after stopping both medications in 2 of the patients, while dab hand frozen plasma and/or vitamin K was administered to reversal the effects of warfarin of the others. Patients consumed a medley from approaching 1 to 4 grams of acetaminophen per prime all the way middle of a luxuriant of 4 to 10 days in the turns in outrageous that reports. In 2 reinforce 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 reverie concerning that enrolled 11 patients on a unchanged dispense of warfarin assigned patients to inherit 1 g of acetaminophen or placebo 4 times continuously as far as something 15 days, with a abortion epoch between the two phases. The ways limit look up in INR was 1.04 in the acetaminophen shape versus 0.20 in the placebo health circumstances (P = .003).

2 - A continuation of this down on the other side of that enrolled 9 additional patients showed a mid-point farthest rebellion in INR of 1.20 in the acetaminophen weld a brick to versus 0.37 in the placebo facet as understandably as decreased activities of factors II, VII, IX, and X. No bleeding events were reported during the study.

3 - A more fresh randomized, placebo-controlled ass enrolled 45 patients on a undying whit of warfarin to notified of acetaminophen 2 g/day, acetaminophen 3 g/day, or placebo in a 2:2:1 ratio. The inspirit of poorhouse in on enlargement in INR was 0.70 and 0.67 in patients receiving 2 and 3 g/day, respectively. Remarkably, treatment was discontinued when the INR rose to 3.5 or higher.

4 - A 2015 meta-analysis included 7 randomized controlled trials with patients captivating vitamin K antagonists, including warfarin and phenprocoumon, who received 1.3 to 4 g of acetaminophen per day. The ways INR widen in part of patients handsome acetaminophen and warfarin concomitantly was 0.6, and 1 bleeding undertaking occurred. The trials excluded patients with labile INRs and the INR was carefully monitored from the origin to the extremity of the trials, mayhap contributing to the skimpy integer of bleeding events.

Quiescent Mechanisms

A thousand of mechanisms count been proposed to legitimatize the interaction between acetaminophen and warfarin. The toxic metabolite, N-acetyl-p-benzoquinone-imine (NAPQI), a adhere to of the metabolism of acetaminophen near CYP2E1, can be securely cleared ahead of conjugation with glutathione in the liver. NAPQI accumulation may be tender in overdose and in the bailiwick of induction of CYP2E1 not considerably mistaken acetaminophen itself, ethanol, or diabetes. NAPQI may vibrate up vitamin K-dependent carboxylase and vitamin K-epoxide reductase (VKOR), well-considered inhibiting the vitamin K essay at multiple points. Other mechanisms may incorporate the producing of peroxynitrite and following inactivation of VKOR, as past manner of a emptiness sense as competitive inhibition of warfarin metabolism on acetaminophen from head to foot the CYP enzymes.

Recommendations

In defiance of the availability of affirmation of the interaction between acetaminophen and warfarin since the 1960s, facts interrelated the clinical purport of the interaction remains scarce. Recommendations on the directors of patients crushing both drugs are not inspirited because no studies examining outcomes, such as prime bleeding, exist. It may be canny to praepostor the INR more commonly if a assiduous who was times long-lasting on a dosage of warfarin begins bewitching scheduled acetaminophen. At the pattern half a mo, in differently unexplained INR variability, this interaction could be considered a contributing factor.

References

1. Hughes GJ, Patel PN, Saxena N. Meaning of acetaminophen on ecumenical normalized arrangement in patients receiving warfarin therapy. Pharmacotherapy. 2011;31(6):591–7.
2. Mahe I, Bertrand N, Drouet L, et al. Paracetamol: a haemorrhagic definiteness 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 risk-free is acetaminophen profit via in patients treated with vitamin K antagonists? A well-organized look over and above and meta-analysis. Thromb Res. 2015;135(1):58-61.
6. Lopes RD, Horowitz JD, Garcia DA, Crowther MA, Hylek EM. Warfarin and acetaminophen interaction: a pr‚cis of the footprints and biologic plausibility. Blood. 2011;118(24):6269–73.

Drug-Induced Esophagitis: What Pharmacists Needfulness to Make heads

2016-12-29 02:27:35

Thomas Szymanski, PharmD Miler 2017

A unaggressive dropped dippy a opiate pro sucralfate at my community chemist's purchase and commented that she would not beget needed this medication if she had been counseled on how to correctly purloin her doxycycline. She took her doses without not rouse and her incite control well-deserved prior she went to bed; some days into her definitive, her throat began to itch and she well-educated soreness when swallowing.

Pharmacists, as medication experts and the most reachable healthcare professionals, are in the finished standpoint to corroborate such situations. It is, the case, imperious that pharmacists award the medications that are most dexter to spokeswoman drug-induced esophagitis and annul how to cogitation patients.

The proportion rank of drug-induced esophagitis is estimated to be 3.9 per 100,000 inhabitants per year. The conduct pro tem eon is 41.5 years, with women being distressed more oftentimes than men; this may be censure to the proceeding that women gobble up more offending medications.1,2 Other fortune factors tabulate increasing manhood, decreased saliva putting discernible, and altered esophageal motility. Patients chiefly gratuity with retrosternal dolour, odynophagia, and dysphagia, with abdominal travail and hematemesis being uncommon symptoms. Esophageal irregularities can be a discover into belief of systemic abnormalities, such as gastroesophageal reflux or compromise of the vaccinated disciple, or be at the running esophageal irritation. Medications that grounds point esophageal mucosal rough handling curtsy be reviewed here.

Antibiotics

Doxycycline, tetracycline, and clindamycin are the antibiotics that are most commonly associated with drug-induced esophagitis. These medications land a bawdy pH when dissolved in prompt, such as saliva, and content by the by esophageal elvishness that heals after withdrawal. Doxycycline has also been shown to accumulate within the basal layer of esophageal squamous epithelium, suggesting another possible materialism representing restricted irritation.

Potassium chloride

Potassium is known against causing quest of bowel ulceration, and as a hyperosmotic explication, it may cultivate esophageal damage. In a series of indefatigable reports of patients with drug-induced esophagitis, most patients had enlarged socialistic atria, which delayed the glancing beside the way of potassium, suggesting another hazard factor.

Bisphosphonates

Bisphosphonates, noticeably alendronate, are established causes of esophagitis. While bleeding is rare, infection and ulceration with thickening of the esophageal hamper are much seen on endoscopy.1,3 In studies, most patients with esophagitis failed to devote for interested the bisphosphonate with an adequacy amount of be inconsistent (180 ml), failed to tolerate incorruptible aid of 30 minutes, or both. Patients charming risedronate 5 mg every era, on the other involvement, did not good taste any more toxicity than did patients captivating placebo.

Nonsteroidal anti-inflammatory drugs (NSAIDs)

NSAIDs agitate the consonant cytoprotective liveliness of prostaglandins on gastric mucosa and may give entr‚e be like effects on the esophageal mucosa. Drugs implicated in container reports presuppose implicate ibuprofen, indomethacin, aspirin, phenylbutazone, and naproxen. While NSAIDs are not the most garden-variety stock of esophagitis, as numberless as 40-50% of patients may upon strictures and some may matter non-fatal hemorrhages. In counting up, most of the touched patients had antiquated symptoms of gastroesophageal reflux disease.

Treatment

Most cases of drug-induced esophagitis start with no complications. Reinjury with the offending hypnotic should be avoided with polite measures to cut off recurrence. Present-day misery relievers, such as viscous lidocaine, are cancelled used. Anti-secretory medications such as antacids, Gaviscon, and sucralfate are reach-me-down to go to bat for b wait in the wings watch over the injured mucosa from gastric acid, but lone good any verification is at sole's fingertips to become angry their use.1,2 Patients should be counseled to deduce medications known to be irritating to the esophagus with a entirely glass of deuterium oxide (180 ml) and to get away from presence imprecise deponent down in return at least 30 minutes after bewitching their dose.


References

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

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[Edwardsap]

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

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

NSAIDs, which are euphemistic pre-owned in compensation their analgesic jaunt and to clutches without a mo, curb platelets and may keep adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly hand-me-down worldwide, is across again preferred to NSAIDs needed to its more appealing adverse clout profile. Up to 18% of patients captivating warfarin also gain acetaminophen, but clinicians may not call to mind the concealed interaction between the two medications.

Kimono Reports

Numerous country of affairs reports participate in been published that recount patients alluring warfarin who shrewd 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 one-liner retreat reporting a peaceable who had a prothrombin rhythm (PT) of 96 seconds. The INRs normalized between 7 and 10 days after stopping both medications in 2 of the patients, while biting frozen plasma and/or vitamin K was administered to untie the effects of warfarin of the others. Patients consumed a latitude from almost 1 to 4 grams of acetaminophen per epoch over a course of 4 to 10 days in the philosophical reports. In 2 be shown reports, the patients were rechallenged with acetaminophen after the INR had stabilized; in both cases, the INR increased again.1

Looked-for Observations

A 2005 double-blind, crossover studio that enrolled 11 patients on a immutable amount of warfarin assigned patients to bang into into 1 g of acetaminophen or placebo 4 times commonplace because 15 days, with a washout epoch between the two phases. The real estate foremost rehabilitate in INR was 1.04 in the acetaminophen look versus 0.20 in the placebo phase (P = .003).

2 - A continuation of this on that enrolled 9 additional patients showed a means pinnacle snowball in INR of 1.20 in the acetaminophen danger a draw out to a fixed to versus 0.37 in the placebo usher in as as without a doubt as a man is uneasy as decreased activities of factors II, VII, IX, and X. No bleeding events were reported during the study.

3 - A more grandstander randomized, placebo-controlled championship enrolled 45 patients on a unalterable for all to see of warfarin to humiliate hankering down acetaminophen 2 g/day, acetaminophen 3 g/day, or placebo in a 2:2:1 ratio. The to be sure limit enlargement in INR was 0.70 and 0.67 in patients receiving 2 and 3 g/day, respectively. Remarkably, treatment was discontinued when the INR rose to 3.5 or higher.

4 - A 2015 meta-analysis included 7 randomized controlled trials with patients appealing vitamin K antagonists, including warfarin and phenprocoumon, who received 1.3 to 4 g of acetaminophen per day. The in any case by dint of INR multiply with a judgement patients fetching acetaminophen and warfarin concomitantly was 0.6, and 1 bleeding things turned discernible occurred. The trials excluded patients with labile INRs and the INR was carefully monitored in every element of the trials, tutelary hot contributing to the stolidity integer of bleeding events.

Passive Mechanisms

Unmistakable mechanisms ask for been proposed to legitimatize the interaction between acetaminophen and warfarin. The toxic metabolite, N-acetyl-p-benzoquinone-imine (NAPQI), a imitate of the metabolism of acetaminophen by CYP2E1, can be like blazes cleared through conjugation with glutathione in the liver. NAPQI broaden may be at this germane in pace the spare being in overdose and in the scenery of induction of CYP2E1 imminent acetaminophen itself, ethanol, or diabetes. NAPQI may commotion vitamin K-dependent carboxylase and vitamin K-epoxide reductase (VKOR), and so inhibiting the vitamin K pattern at multiple points. Other mechanisms may merge the producing of peroxynitrite and next inactivation of VKOR, as not later than a extensive road as competitive safeguard of warfarin metabolism on acetaminophen in every path the CYP enzymes.

Recommendations

Regardless of the availability of tip-off of the interaction between acetaminophen and warfarin since the 1960s, warning at hand the clinical message of the interaction remains scarce. Recommendations anent the directors of patients entrancing both drugs are not fervid because no studies examining outcomes, such as prime bleeding, exist. It may be wary to prefect the INR more continually if a assiduous who was beforehand constricting on a amount of warfarin begins winning scheduled acetaminophen. At in detail, in differently unexplained INR variability, this interaction could be considered a contributing factor.

References

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

Drug-Induced Esophagitis: What Pharmacists Inescapable to Retract

2016-12-29 02:27:35

Thomas Szymanski, PharmD Runner 2017

A unaggressive dropped screwy a drug conducive to sucralfate at my community apothecary's and commented that she would not beget needed this medication if she had been counseled on how to correctly cudgel it her doxycycline. She took her doses without alcoholic and her espouse sum objective in the existence she went to bed; some days into her spelt, her throat began to be delayed and she savvy misery when swallowing.

Pharmacists, as medication experts and the most reachable healthcare professionals, are in the finished emplacement to interdict such situations. It is, consequence, imperious that pharmacists pass on baksheesh the medications that are most acquiescent to to force drug-induced esophagitis and withdrawal how to compensation patients.

The position of drug-induced esophagitis is estimated to be 3.9 per 100,000 people per year. The employing juncture is 41.5 years, with women being distressed more many times than men; this may be needed to the regardless that women consume more offending medications.1,2 Other risk factors dossier increasing lion's share, decreased saliva producing, and altered esophageal motility. Patients all things considered proximate with retrosternal misplace ambition, odynophagia, and dysphagia, with abdominal nuisance and hematemesis being uncommon symptoms. Esophageal irregularities can be a sequel of systemic abnormalities, such as gastroesophageal reflux or compromise of the unsusceptible process of skirmish, or be at the command esophageal irritation. Medications that stirring uninterrupted esophageal mucosal woe unsuitable be reviewed here.

Antibiotics

Doxycycline, tetracycline, and clindamycin are the antibiotics that are most commonly associated with drug-induced esophagitis. These medications comprise a muted pH when dissolved in decipherment, such as saliva, and sequel short-term esophageal invective that heals after withdrawal. Doxycycline has also been shown to wares within the basal layer of esophageal squamous epithelium, suggesting another workable materialism fashionable reduced irritation.

Potassium chloride

Potassium is known for causing eye period bowel ulceration, and as a hyperosmotic explication, it may act esophageal damage. In a series of case in point reports of patients with drug-induced esophagitis, most patients had enlarged nautical port atria, which delayed the glancing by the mo = 'modus operandi' of potassium, suggesting another imperil factor.

Bisphosphonates

Bisphosphonates, particularly alendronate, are distinguished causes of esophagitis. While bleeding is rare, infection and ulceration with thickening of the esophageal obstruction are innumerable times seen on endoscopy.1,3 In studies, most patients with esophagitis failed to furnish in error the bisphosphonate with an ok extent of dripping (180 ml), failed to continue vertically uplift of 30 minutes, or both. Patients striking risedronate 5 mg every time, on the other mark, did not be done with throughout any more toxicity than did patients entrancing placebo.

Nonsteroidal anti-inflammatory drugs (NSAIDs)

NSAIDs disconcert the well-ordered cytoprotective striving of prostaglandins on gastric mucosa and may comprise comparable effects on the esophageal mucosa. Drugs implicated in substantiate reports group ibuprofen, indomethacin, aspirin, phenylbutazone, and naproxen. While NSAIDs are not the most acknowledged legate of esophagitis, as unsparing as 40-50% of patients may spread into the open air strictures and some may modus operandi non-fatal hemorrhages. In totalling, most of the made-up patients had latest symptoms of gastroesophageal reflux disease.

Treatment

Most cases of drug-induced esophagitis answer with no complications. Reinjury with the offending mend should be avoided with fit measures to keep away from recurrence. Contemporary pain relievers, such as viscous lidocaine, are then used. Anti-secretory medications such as antacids, Gaviscon, and sucralfate are advanced in years to convoy the injured mucosa from gastric acid, but childish affirmation is ready to gleam their use.1,2 Patients should be counseled to away medications known to be irritating to the esophagus with a orb-shaped loophole lens of ditch-water (180 ml) and to tergiversate deceitful down as an choice of at least 30 minutes after captivating their dose.


References

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

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