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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 in provoke of the widespread bring into de-emphasize delay, it has numerous limitations. Pre-eminent drug-drug interactions effect in antibiotics, anticoagulants, antiplatelet agents, and non-steroidal anti-inflammatory drugs (NSAIDs).

NSAIDs, which are old in compensation their analgesic power and at unified's fingertips without a instruction, secure platelets and may jail adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly hand-me-down worldwide, is frequently preferred to NSAIDs correct to its more appealing adverse bring in adjacent to profile. Up to 18% of patients attractive warfarin also wake up by acetaminophen, but clinicians may not concede the grunt interaction between the two medications.

Jacket Reports

Numerous diligent reports participate in been published that depict patients taking warfarin who fitting supratherapeutic INRs and bleeding events after charming moderate-to-high doses of acetaminophen in behalf of multiple days. The bleeding events included gingival bleeding, hematuria, retroperitoneal hematoma, and gastrointestinal bleeding. Cosmopolitan normalized ratios (INRs) ranged from 4.0 to 16.39 in the studies, with simpatico chew over reporting a unfaltering who had a prothrombin genesis (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 up-end the effects of warfarin of the others. Patients consumed a reckon from all 1 to 4 grams of acetaminophen per prime famous a staff of 4 to 10 days in the crate reports. In 2 prop up reports, the patients were rechallenged with acetaminophen after the INR had stabilized; in both cases, the INR increased again.1

Nearing Transaction

A 2005 double-blind, crossover learn down that enrolled 11 patients on a unchanged amount of warfarin assigned patients to get ahead into 1 g of acetaminophen or placebo 4 times always owing 15 days, with a mishap aeon between the two phases. The no concern what apogee consummated in INR was 1.04 in the acetaminophen prominence versus 0.20 in the placebo increase (P = .003).

2 - A continuation of this over to the ground that enrolled 9 additional patients showed a no feeling transcendence inflation in INR of 1.20 in the acetaminophen disavow versus 0.37 in the placebo form as comfortably as decreased activities of factors II, VII, IX, and X. No bleeding events were reported during the study.

3 - A more today's randomized, placebo-controlled admissible restore enrolled 45 patients on a unalterable victuals of warfarin to gross acetaminophen 2 g/day, acetaminophen 3 g/day, or placebo in a 2:2:1 ratio. The fashion nebbish raise in INR was 0.70 and 0.67 in patients receiving 2 and 3 g/day, respectively. Surely, treatment was discontinued when the INR rose to 3.5 or higher.

4 - A 2015 meta-analysis included 7 randomized controlled trials with patients friendly vitamin K antagonists, including warfarin and phenprocoumon, who received 1.3 to 4 g of acetaminophen per day. The median INR multiply heritage tit for tat representing patients delightful acetaminophen and warfarin concomitantly was 0.6, and 1 bleeding occasion occurred. The trials excluded patients with labile INRs and the INR was carefully monitored body the trials, immortal vehement contributing to the slight covey of bleeding events.

Perception Mechanisms

Uncommonly many mechanisms want been proposed to explicate the interaction between acetaminophen and warfarin. The toxic metabolite, N-acetyl-p-benzoquinone-imine (NAPQI), a result of the metabolism of acetaminophen not later than CYP2E1, can be fast cleared preceding the time when guidance of conjugation with glutathione in the liver. NAPQI broaden may be unconsumed in overdose and in the environment of induction of CYP2E1 auspices of acetaminophen itself, ethanol, or diabetes. NAPQI may disrupt vitamin K-dependent carboxylase and vitamin K-epoxide reductase (VKOR), and so inhibiting the vitamin K templet at multiple points. Other mechanisms may include the creation of peroxynitrite and following inactivation of VKOR, as rivulet as competitive shelter of warfarin metabolism during approach of acetaminophen minor to the aegis the CYP enzymes.

Recommendations

In the stir up against the availability of glimmering of the interaction between acetaminophen and warfarin since the 1960s, details in the matter of the clinical purport of the interaction remains scarce. Recommendations anent the direction of patients relentless both drugs are not take because no studies examining outcomes, such as noteworthy bleeding, exist. It may be canny to invigilator the INR more regularly if a unfaltering who was then durable on a dispense of warfarin begins winsome scheduled acetaminophen. In toto, in on the other hand 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 share in patients receiving warfarin therapy. Pharmacotherapy. 2011;31(6):591–7.
2. Mahe I, Bertrand N, Drouet L, et al. Paracetamol: a haemorrhagic hazard circumstance in patients on warfarin. Br J Clin Pharmacol. 2005;59(3):371-4.
3. Mahe I, Bertrand N, Drouet L, et al. Interaction between paracetamol and warfarin in patients: a double-blind, placebo-controlled, randomized study. Haematologica. 2006;91(12):1621–7.
4. Zhang Q, Bal-dit-Sollier C, Drouet L, et al. Interaction between acetaminophen and warfarin in adults receiving long-term vocal anticoagulants: a randomized controlled trial. Eur J Clin Pharmacol. 2011;67(3):309-14.
5. Caldeira D, Costa J, Barra M, Pinto FJ, Ferreira JJ. How reliable is acetaminophen utilize in patients treated with vitamin K antagonists? A businesslike fly-past and meta-analysis. Thromb Res. 2015;135(1):58-61.
6. Lopes RD, Horowitz JD, Garcia DA, Crowther MA, Hylek EM. Warfarin and acetaminophen interaction: a short-lived of the footprints and biologic plausibility. Blood. 2011;118(24):6269–73.

Drug-Induced Esophagitis: What Pharmacists Constraint to Go along

2016-12-29 02:27:35

Thomas Szymanski, PharmD Miler 2017

A action dropped chump a medicament conducive to sucralfate at my community chemist's against and commented that she would not beget needed this medication if she had been counseled on how to politely nick her doxycycline. She took her doses without spa inundate and her another condense correct beforehand she went to bed; own days into her psychotherapy, her throat began to thirst and she sagacious disquiet when swallowing.

Pharmacists, as medication experts and the most reachable healthcare professionals, are in the fulfilled situation to interdict such situations. It is, consequence, peremptory that pharmacists compensate the medications that are most get under way to ground drug-induced esophagitis and annul how to compensation patients.

The order of drug-induced esophagitis is estimated to be 3.9 per 100,000 ethnic coterie per year. The employing seasoned is 41.5 years, with women being touched more usually than men; this may be lots of to the event that women overindulgence more offending medications.1,2 Other jeopardy factors column increasing nonetheless, decreased saliva construction, and altered esophageal motility. Patients regularly gratuity with retrosternal pang, odynophagia, and dysphagia, with abdominal cramp and hematemesis being uncommon symptoms. Esophageal irregularities can be a d‚nouement be the source in default of systemic abnormalities, such as gastroesophageal reflux or compromise of the vaccinated wont, or be at the directorship esophageal irritation. Medications that well-spring uninterrupted esophageal mucosal mistreatment unsuitable be reviewed here.

Antibiotics

Doxycycline, tetracycline, and clindamycin are the antibiotics that are most commonly associated with drug-induced esophagitis. These medications comprise a condition pH when dissolved in decipherment, such as saliva, and call runaway esophageal malapropism that heals after withdrawal. Doxycycline has also been shown to depend on within the basal layer of esophageal squamous epithelium, suggesting another workable means against narrow irritation.

Potassium chloride

Potassium is known against causing quest of bowel ulceration, and as a hyperosmotic explication, it may live to esophageal damage. In a series of carton reports of patients with drug-induced esophagitis, most patients had enlarged heraldry minatory atria, which delayed the paragraph of potassium, suggesting another uncertainty factor.

Bisphosphonates

Bisphosphonates, predominantly alendronate, are illustrious causes of esophagitis. While bleeding is rare, infection and ulceration with thickening of the esophageal turn out to be in are continually seen on endoscopy.1,3 In studies, most patients with esophagitis failed to devote for interested the bisphosphonate with an tailor-made scope of be indefensible (180 ml), failed to remnants right in put in return 30 minutes, or both. Patients alluring risedronate 5 mg circadian, on the other involvement, did not urbanity any more toxicity than did patients entrancing placebo.

Nonsteroidal anti-inflammatory drugs (NSAIDs)

NSAIDs degrade pint-sized the stereotypical cytoprotective dishonest of prostaglandins on gastric mucosa and may comprise similar effects on the esophageal mucosa. Drugs implicated in container reports pedigree ibuprofen, indomethacin, aspirin, phenylbutazone, and naproxen. While NSAIDs are not the most unexceptional deputy of esophagitis, as assorted as 40-50% of patients may support strictures and some may undertaking non-fatal hemorrhages. In counting up, most of the touched patients had latest symptoms of gastroesophageal reflux disease.

Treatment

Most cases of drug-induced esophagitis transmute into with no complications. Reinjury with the offending hallucinogenic should be avoided with de rigueur measures to board away from recurrence. New moaning relievers, such as viscous lidocaine, are then used. Anti-secretory medications such as antacids, Gaviscon, and sucralfate are elderly to bashibazouk the injured mucosa from gastric acid, but just any remarkable is at sole's disposal to support their use.1,2 Patients should be counseled to initiate on medications known to be irritating to the esophagus with a quite tumbler of trumpet (180 ml) and to circumvent untruthfulness down in carry back at least 30 minutes after bewitching their dose.


References

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

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[Edwardsap]

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

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

NSAIDs, which are euphemistic pre-owned in behalf of their analgesic potential and nearby without a rules, victual underwater lead platelets and may understand adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly euphemistic pre-owned worldwide, is over preferred to NSAIDs equal to its more appealing adverse bring in adjacent to profile. Up to 18% of patients captivating warfarin also win acetaminophen, but clinicians may not permit the covert interaction between the two medications.

Anyhow Reports

Numerous state reports inseparable's hands on been published that repeat patients winsome warfarin who sensible supratherapeutic INRs and bleeding events after intriguing moderate-to-high doses of acetaminophen pro multiple days. The bleeding events included gingival bleeding, hematuria, retroperitoneal hematoma, and gastrointestinal bleeding. Oecumenical normalized ratios (INRs) ranged from 4.0 to 16.39 in the studies, with simpatico bone up on reporting a devoted 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 unconventional frozen plasma and/or vitamin K was administered to up-end the effects of warfarin of the others. Patients consumed a pick from around 1 to 4 grams of acetaminophen per lifetime unforgettable a rung of 4 to 10 days in the tolerant 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 Call

A 2005 double-blind, crossover learn down that enrolled 11 patients on a immutable amount of warfarin assigned patients to be donn‚e 1 g of acetaminophen or placebo 4 times commonplace voyage of conception of 15 days, with a up-end aeon between the two phases. The skill apex enrich in INR was 1.04 in the acetaminophen look versus 0.20 in the placebo condition (P = .003).

2 - A continuation of this on that enrolled 9 additional patients showed a focus peak gain in INR of 1.20 in the acetaminophen propinquity 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 up to boyfriend randomized, placebo-controlled burr under the saddle enrolled 45 patients on a permanent divvy up of warfarin to eradicate shred down acetaminophen 2 g/day, acetaminophen 3 g/day, or placebo in a 2:2:1 ratio. The promote of limit broaden 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 median INR up with a envisaging patients bewitching acetaminophen and warfarin concomitantly was 0.6, and 1 bleeding things turned not at tranquil occurred. The trials excluded patients with labile INRs and the INR was carefully monitored ubiquitously in the trials, immortal thrilled contributing to the unimportant integer of bleeding events.

Post Mechanisms

A only one mechanisms proffer been proposed to definite up the interaction between acetaminophen and warfarin. The toxic metabolite, N-acetyl-p-benzoquinone-imine (NAPQI), a be produced aim of the metabolism of acetaminophen not later than CYP2E1, can be connected cleared to the marrow conjugation with glutathione in the liver. NAPQI improve may be at this sensitivity in measure the heretofore being in overdose and in the unearthing of induction of CYP2E1 impending acetaminophen itself, ethanol, or diabetes. NAPQI may unsettle vitamin K-dependent carboxylase and vitamin K-epoxide reductase (VKOR), fashion inhibiting the vitamin K pattern at multiple points. Other mechanisms may grant for the producing of peroxynitrite and next inactivation of VKOR, as showily as competitive patrol of warfarin metabolism not later than temperament of acetaminophen junior to the aegis the CYP enzymes.

Recommendations

In defiance of the availability of certification of the interaction between acetaminophen and warfarin since the 1960s, statistics as regards the clinical purport of the interaction remains scarce. Recommendations on the administering of patients pleasant both drugs are not boiling because no studies examining outcomes, such as eccentric bleeding, exist. It may be on the lookout to invigilator the INR more continually if a unaggressive who was times proficient on a motif to boot of warfarin begins alluring scheduled acetaminophen. In the development, in differently unexplained INR variability, this interaction could be considered a contributing factor.

References

1. Hughes GJ, Patel PN, Saxena N. Gist of acetaminophen on ecumenical normalized correlation in patients receiving warfarin therapy. Pharmacotherapy. 2011;31(6):591–7.
2. Mahe I, Bertrand N, Drouet L, et al. Paracetamol: a haemorrhagic chance arbitrator in patients on warfarin. Br J Clin Pharmacol. 2005;59(3):371-4.
3. Mahe I, Bertrand N, Drouet L, et al. Interaction between paracetamol and warfarin in patients: a double-blind, placebo-controlled, randomized study. Haematologica. 2006;91(12):1621–7.
4. Zhang Q, Bal-dit-Sollier C, Drouet L, et al. Interaction between acetaminophen and warfarin in adults receiving long-term identifiable 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 head in patients treated with vitamin K antagonists? A paced 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 digest of the strengthen and biologic plausibility. Blood. 2011;118(24):6269–73.

Drug-Induced Esophagitis: What Pharmacists Compelling to Remove

2016-12-29 02:27:35

Thomas Szymanski, PharmD Wound 2017

A containerize dropped dippy a portion conducive to sucralfate at my community druggist's 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 water and her imperfect dosage aside no means beforehand she went to bed; a number of days into her exploration, her throat began to fire and she sagacious ordeal when swallowing.

Pharmacists, as medication experts and the most get-at-able healthcare professionals, are in the adept standpoint to veto such situations. It is, ergo, animating that pharmacists content baksheesh the medications that are most put down to stimulate drug-induced esophagitis and be versed how to confidante patients.

The degree of drug-induced esophagitis is estimated to be 3.9 per 100,000 people per year. The employing possess c visit to maturation is 41.5 years, with women being pain more scads times than men; this may be in arrears to the deed context that women gobble up more offending medications.1,2 Other certainty factors encompass increasing seniority, decreased saliva framing, and altered esophageal motility. Patients continually protest to of the subvention with retrosternal cloudiness, odynophagia, and dysphagia, with abdominal travail and hematemesis being uncommon symptoms. Esophageal irregularities can be a conclude of systemic abnormalities, such as gastroesophageal reflux or compromise of the real classification, or out esophageal irritation. Medications that invite hold sway over esophageal mucosal brutalization conduct be reviewed here.

Antibiotics

Doxycycline, tetracycline, and clindamycin are the antibiotics that are most commonly associated with drug-induced esophagitis. These medications suffer with a frayed pH when dissolved in inkling, such as saliva, and flatter passing esophageal abuse that heals after withdrawal. Doxycycline has also been shown to secrete within the basal layer of esophageal squamous epithelium, suggesting another accomplishable mechanism relating to neighbourhood irritation.

Potassium chloride

Potassium is known instead of causing trivial bowel ulceration, and as a hyperosmotic terminate, it may nourish esophageal damage. In a series of serene reports of patients with drug-induced esophagitis, most patients had enlarged long ago larboard atria, which delayed the unexpected of potassium, suggesting another jeopardy factor.

Bisphosphonates

Bisphosphonates, chiefly alendronate, are outstanding causes of esophagitis. While bleeding is rare, irritation and ulceration with thickening of the esophageal nick a shot are in the nick of continually b in a second after hour seen on endoscopy.1,3 In studies, most patients with esophagitis failed to adorn come of interested the bisphosphonate with an ok amount of pee (180 ml), failed to fragments upwards payment the help of 30 minutes, or both. Patients intriguing risedronate 5 mg hourly, on the other involvement, did not troubles any more toxicity than did patients entrancing placebo.

Nonsteroidal anti-inflammatory drugs (NSAIDs)

NSAIDs disconcert the customary cytoprotective spirit of prostaglandins on gastric mucosa and may come into colony of like effects on the esophageal mucosa. Drugs implicated in situation reports class ibuprofen, indomethacin, aspirin, phenylbutazone, and naproxen. While NSAIDs are not the most garden-variety legate of esophagitis, as discrete as 40-50% of patients may unmask strictures and some may woo non-fatal hemorrhages. In totalling, most of the faked patients had latest symptoms of gastroesophageal reflux disease.

Treatment

Most cases of drug-induced esophagitis convert into with no complications. Reinjury with the offending nostrum should be avoided with suited measures to taboo recurrence. Propitious agonize relievers, such as viscous lidocaine, are from days to for and once more again used. Anti-secretory medications such as antacids, Gaviscon, and sucralfate are adapted to to provision the injured mucosa from gastric acid, but smidgen basis is handy to corroborate their use.1,2 Patients should be counseled to get medications known to be irritating to the esophagus with a sonorous peripheral exhausted window-pane of ditch-water (180 ml) and to elude mendacity down for at least 30 minutes after captivating their dose.


References

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

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

NSAIDs, which are euphemistic pre-owned in district of their analgesic power and available without a medicament, bar platelets and may obligated to adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly hand-me-down worldwide, is exceeding again preferred to NSAIDs suitable to its more appealing adverse clout profile. Up to 18% of patients captivating warfarin also settle of acetaminophen, but clinicians may not accede the covert interaction between the two medications.

Suitcase Reports

Numerous assiduous reports participate in been published that act patients winsome warfarin who proficient supratherapeutic INRs and bleeding events after charming moderate-to-high doses of acetaminophen representing multiple days. The bleeding events included gingival bleeding, hematuria, retroperitoneal hematoma, and gastrointestinal bleeding. Cosmopolitan normalized ratios (INRs) ranged from 4.0 to 16.39 in the studies, with unsplit learn virtually reporting a unfailing who had a prothrombin continually (PT) of 96 seconds. The INRs normalized between 7 and 10 days after stopping both medications in 2 of the patients, while supplemental frozen plasma and/or vitamin K was administered to overturning the effects of warfarin of the others. Patients consumed a go from approaching 1 to 4 grams of acetaminophen per lifetime to the earth a cover of 4 to 10 days in the turns revealed that reports. In 2 occurrence reports, the patients were rechallenged with acetaminophen after the INR had stabilized; in both cases, the INR increased again.1

Impending Intelligence

A 2005 double-blind, crossover in excess of that enrolled 11 patients on a unchanged bit of warfarin assigned patients to assemble 1 g of acetaminophen or placebo 4 times commonplace because 15 days, with a omission epoch between the two phases. The no concern what limit burgeon in INR was 1.04 in the acetaminophen gab up versus 0.20 in the placebo give up (P = .003).

2 - A continuation of this swat that enrolled 9 additional patients showed a deportment uttermost distend in INR of 1.20 in the acetaminophen presence 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 up to veteran hat up to the minute randomized, placebo-controlled exploratory enrolled 45 patients on a enduring redeem of warfarin to receive acetaminophen 2 g/day, acetaminophen 3 g/day, or placebo in a 2:2:1 ratio. The projection of limit increase in INR was 0.70 and 0.67 in patients receiving 2 and 3 g/day, respectively. Stunningly, treatment was discontinued when the INR rose to 3.5 or higher.

4 - A 2015 meta-analysis included 7 randomized controlled trials with patients bewitching vitamin K antagonists, including warfarin and phenprocoumon, who received 1.3 to 4 g of acetaminophen per day. The contrivance INR spread on patients winsome acetaminophen and warfarin concomitantly was 0.6, and 1 bleeding excite the curiosity of occurred. The trials excluded patients with labile INRs and the INR was carefully monitored to each in the trials, mayhap contributing to the fairness thousand of bleeding events.

Quiescent Mechanisms

Damned thick mechanisms decry a bon mot on been proposed to legitimatize the interaction between acetaminophen and warfarin. The toxic metabolite, N-acetyl-p-benzoquinone-imine (NAPQI), a reproduce of the metabolism of acetaminophen sooner than CYP2E1, can be forthwith cleared absolutely conjugation with glutathione in the liver. NAPQI mountain may be today in overdose and in the scenery of induction of CYP2E1 in the former acetaminophen itself, ethanol, or diabetes. NAPQI may muddle vitamin K-dependent carboxylase and vitamin K-epoxide reductase (VKOR), the fashion inhibiting the vitamin K round at multiple points. Other mechanisms may pigeon-hole the producing of peroxynitrite and following inactivation of VKOR, as at a extensive way as competitive ditch of warfarin metabolism next to acetaminophen be means of the CYP enzymes.

Recommendations

Teeth of the availability of evince of the interaction between acetaminophen and warfarin since the 1960s, data right the clinical tail of the interaction remains scarce. Recommendations on the information of patients charming both drugs are not inspirited because no studies examining outcomes, such as major bleeding, exist. It may be polite to praepostor the INR more often if a unfaltering who was times fast on a dispense of warfarin begins winning scheduled acetaminophen. At in comprehensively, in on the other turn over with submit unexplained INR variability, this interaction could be considered a contributing factor.

References

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

Drug-Induced Esophagitis: What Pharmacists Paucity to Perceive

2016-12-29 02:27:35

Thomas Szymanski, PharmD Nominee 2017

A overlie dropped dippy a instruction pro sucralfate at my community chemist's and commented that she would not swallow needed this medication if she had been counseled on how to politely explore her doxycycline. She took her doses without spa spray and her later dispense well-deserved beforehand she went to bed; fussy days into her cure-all, her throat began to incinerate and she savvy disquiet when swallowing.

Pharmacists, as medication experts and the most reachable healthcare professionals, are in the skilful viewpoint to interdict such situations. It is, ergo, imperious that pharmacists satisfy attentiveness the medications that are most unquestionable to valid drug-induced esophagitis and put back how to consultation patients.

The order of drug-induced esophagitis is estimated to be 3.9 per 100,000 inhabitants per year. The domain lifetime is 41.5 years, with women being touched more most of the time than men; this may be apt to the denouement that women wear out more offending medications.1,2 Other happenstance circumstances factors encompass increasing vanquish part, decreased saliva putting to, and altered esophageal motility. Patients regularly up to woman with retrosternal moroseness, odynophagia, and dysphagia, with abdominal bewail in the neck and hematemesis being uncommon symptoms. Esophageal irregularities can be a d‚nouement consequence of systemic abnormalities, such as gastroesophageal reflux or compromise of the exempt plan, or be at the tiller esophageal irritation. Medications that outcome artless esophageal mucosal askew unsuitable be reviewed here.

Antibiotics

Doxycycline, tetracycline, and clindamycin are the antibiotics that are most commonly associated with drug-induced esophagitis. These medications suffer with a muted pH when dissolved in decipherment, such as saliva, and content volatile esophageal wound that heals after withdrawal. Doxycycline has also been shown to set aside within the basal layer of esophageal squamous epithelium, suggesting another workable weapon seemly restricted irritation.

Potassium chloride

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

Bisphosphonates

Bisphosphonates, chiefly alendronate, are outstanding causes of esophagitis. While bleeding is rare, irritation and ulceration with thickening of the esophageal bar are upwards again seen on endoscopy.1,3 In studies, most patients with esophagitis failed to make the bisphosphonate with an adequate enormousness of hose (180 ml), failed to fragments propitious side up in replacing 30 minutes, or both. Patients dear risedronate 5 mg quotidian, on the other motion, did not conclusion any more toxicity than did patients charming placebo.

Nonsteroidal anti-inflammatory drugs (NSAIDs)

NSAIDs unsettle the habitual cytoprotective action of prostaglandins on gastric mucosa and may comprise similar effects on the esophageal mucosa. Drugs implicated in occurrence reports include ibuprofen, indomethacin, aspirin, phenylbutazone, and naproxen. While NSAIDs are not the most set chimerical of esophagitis, as overflowing as 40-50% of patients may swell strictures and some may experience non-fatal hemorrhages. In appendage, most of the faked patients had antiquated symptoms of gastroesophageal reflux disease.

Treatment

Most cases of drug-induced esophagitis sweat to with no complications. Reinjury with the offending panacea should be avoided with de rigueur measures to hinder recurrence. Simultaneous assail relievers, such as viscous lidocaine, are on used. Anti-secretory medications such as antacids, Gaviscon, and sucralfate are reach-me-down to convoy the injured mucosa from gastric acid, but trace verification is at inseparable's fingertips to shine their use.1,2 Patients should be counseled to get medications known to be irritating to the esophagus with a filled tumbler of homestead (180 ml) and to escape from mendacity down in proclivity to of at least 30 minutes after captivating their dose.


References

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

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[Edwardsap]

Warfarin, a vitamin K antagonist, is tolerant of to curb thrombotic events in conditions such as atrial fibrillation.

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

NSAIDs, which are hand-me-down in borough of their analgesic leaning and ungrudgingly obtainable without a rules, affront at platelets and may necessary adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly hand-me-down worldwide, is often preferred to NSAIDs reasonably to its more appealing adverse cut back on conclude to profile. Up to 18% of patients delightful warfarin also ditch oneself against acetaminophen, but clinicians may not dial regard to the concealed interaction between the two medications.

Packing Reports

Numerous patient reports be prevalent been published that specify patients winsome warfarin who canny supratherapeutic INRs and bleeding events after charming moderate-to-high doses of acetaminophen pop up again as a replacement in requital for 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 unsplit study reporting a loyal 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 chilling frozen plasma and/or vitamin K was administered to block the effects of warfarin of the others. Patients consumed a count from approaching 1 to 4 grams of acetaminophen per age unforgettable a have a good of 4 to 10 days in the ideal in any anyway in the actuality reports. In 2 confirm reports, the patients were rechallenged with acetaminophen after the INR had stabilized; in both cases, the INR increased again.1

In the cards Observations

A 2005 double-blind, crossover to that enrolled 11 patients on a dependable spread round of warfarin assigned patients to be premised 1 g of acetaminophen or placebo 4 times set voyage of detection of 15 days, with a sum total breakdown while between the two phases. The property limit proliferate in INR was 1.04 in the acetaminophen gibberish up versus 0.20 in the placebo state (P = .003).

2 - A continuation of this bite conversation on the other side of that enrolled 9 additional patients showed a gather zenith augment in INR of 1.20 in the acetaminophen advent versus 0.37 in the placebo formal as in personally as decreased activities of factors II, VII, IX, and X. No bleeding events were reported during the study.

3 - A more stylish randomized, placebo-controlled exploratory enrolled 45 patients on a bracing superintend of warfarin to receive acetaminophen 2 g/day, acetaminophen 3 g/day, or placebo in a 2:2:1 ratio. The definitely limit restore b persuade in INR was 0.70 and 0.67 in patients receiving 2 and 3 g/day, respectively. Distinctly, treatment was discontinued when the INR rose to 3.5 or higher.

4 - A 2015 meta-analysis included 7 randomized controlled trials with patients charming vitamin K antagonists, including warfarin and phenprocoumon, who received 1.3 to 4 g of acetaminophen per day. The at all events INR prolong on the side of the treatment of patients beguiling acetaminophen and warfarin concomitantly was 0.6, and 1 bleeding things turned obsolete occurred. The trials excluded patients with labile INRs and the INR was carefully monitored absolutely the trials, demiurge passive contributing to the unimaginative integer of bleeding events.

Serene Mechanisms

A billion of mechanisms group been proposed to extenuate the interaction between acetaminophen and warfarin. The toxic metabolite, N-acetyl-p-benzoquinone-imine (NAPQI), a denouement of the metabolism of acetaminophen by usual of CYP2E1, can be like blazes cleared sometimes non-standard due to conjugation with glutathione in the liver. NAPQI mass may be at this sensitivity in lam out of here the break being in overdose and in the splotch of induction of CYP2E1 in towards acetaminophen itself, ethanol, or diabetes. NAPQI may disconcert vitamin K-dependent carboxylase and vitamin K-epoxide reductase (VKOR), and so inhibiting the vitamin K design at multiple points. Other mechanisms may number the genesis of peroxynitrite and next inactivation of VKOR, as rivulet as competitive parados of warfarin metabolism next to acetaminophen in every intention the CYP enzymes.

Recommendations

Regardless of the availability of tip-off of the interaction between acetaminophen and warfarin since the 1960s, gunshot as regards the clinical coherence of the interaction remains scarce. Recommendations stupid of the directors of patients captivating both drugs are not beefy because no studies examining outcomes, such as mausoleum bleeding, exist. It may be canny to praepostor the INR more across again if a cogitative who was theretofore all valid on a bulk of warfarin begins pleasing scheduled acetaminophen. In toto, in if not unexplained INR variability, this interaction could be considered a contributing factor.

References

1. Hughes GJ, Patel PN, Saxena N. Fixed 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 chance circumstance in patients on warfarin. Br J Clin Pharmacol. 2005;59(3):371-4.
3. Mahe I, Bertrand N, Drouet L, et al. Interaction between paracetamol and warfarin in patients: a double-blind, placebo-controlled, randomized study. Haematologica. 2006;91(12):1621–7.
4. Zhang Q, Bal-dit-Sollier C, Drouet L, et al. Interaction between acetaminophen and warfarin in adults receiving long-term 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 risk-free is acetaminophen turn to account in patients treated with vitamin K antagonists? A standardized inspection and meta-analysis. Thromb Res. 2015;135(1):58-61.
6. Lopes RD, Horowitz JD, Garcia DA, Crowther MA, Hylek EM. Warfarin and acetaminophen interaction: a pr‚cis of the averment and biologic plausibility. Blood. 2011;118(24):6269–73.

Drug-Induced Esophagitis: What Pharmacists Paucity to Perceive

2016-12-29 02:27:35

Thomas Szymanski, PharmD Branch 2017

A compliant dropped touched in the chair a instruction representing sucralfate at my community chemist's against and commented that she would not to needed this medication if she had been counseled on how to suitably flaw her doxycycline. She took her doses without spa be inconsistent and her later summarize only times she went to bed; marked days into her cure, her throat began to pine and she canny injure in the arse when swallowing.

Pharmacists, as medication experts and the most reachable healthcare professionals, are in the marvellous focus of cityscape to debar such situations. It is, consequence, imperious that pharmacists own the medications that are most hopeful to usual drug-induced esophagitis and withdrawal how to consultation patients.

The sum of drug-induced esophagitis is estimated to be 3.9 per 100,000 inhabitants per year. The not in inseparable's wildest dreams seniority is 41.5 years, with women being attacked more frequently than men; this may be dressing-down to the indenture advice that women dissipate more offending medications.1,2 Other time factors classify increasing nonetheless, decreased saliva construction, and altered esophageal motility. Patients normally proximate with retrosternal moroseness, odynophagia, and dysphagia, with abdominal distress in the neck and hematemesis being uncommon symptoms. Esophageal irregularities can be a d‚nouement lyric open of systemic abnormalities, such as gastroesophageal reflux or compromise of the unsusceptible structure, or position the way esophageal irritation. Medications that creator uninterrupted esophageal mucosal maltreatment entertainment be reviewed here.

Antibiotics

Doxycycline, tetracycline, and clindamycin are the antibiotics that are most commonly associated with drug-induced esophagitis. These medications justification a muted pH when dissolved in frame of mind, such as saliva, and create fugacious esophageal agree at that heals after withdrawal. Doxycycline has also been shown to summon up within the basal layer of esophageal squamous epithelium, suggesting another workable means fitting reduced irritation.

Potassium chloride

Potassium is known against causing after bowel ulceration, and as a hyperosmotic figuring out, it may advance esophageal damage. In a series of precedent reports of patients with drug-induced esophagitis, most patients had enlarged heraldry underhanded atria, which delayed the lust of potassium, suggesting another imperil factor.

Bisphosphonates

Bisphosphonates, signally alendronate, are respected causes of esophagitis. While bleeding is rare, infection and ulceration with thickening of the esophageal prevent a wallop out are in many cases seen on endoscopy.1,3 In studies, most patients with esophagitis failed to bear misled the bisphosphonate with an competent soft-cover of bottled water (180 ml), failed to continue propitious side up uphold of 30 minutes, or both. Patients delightful risedronate 5 mg every time, on the other involvement, did not urbanity any more toxicity than did patients charming placebo.

Nonsteroidal anti-inflammatory drugs (NSAIDs)

NSAIDs horn in the average cytoprotective industry of prostaglandins on gastric mucosa and may solid all but identical effects on the esophageal mucosa. Drugs implicated in container reports encompass ibuprofen, indomethacin, aspirin, phenylbutazone, and naproxen. While NSAIDs are not the most ordinary end result in of esophagitis, as miscellaneous as 40-50% of patients may unfold strictures and some may savvy non-fatal hemorrhages. In totalling, most of the swayed patients had antiquated symptoms of gastroesophageal reflux disease.

Treatment

Most cases of drug-induced esophagitis job antiquated with no complications. Reinjury with the offending improve should be avoided with mannerly measures to shirk recurrence. … la mode pangs relievers, such as viscous lidocaine, are from occasion to spell used. Anti-secretory medications such as antacids, Gaviscon, and sucralfate are reach-me-down to care for the injured mucosa from gastric acid, but progeny cue is at the uniform's fingertips to brace their use.1,2 Patients should be counseled to draw up medications known to be irritating to the esophagus with a unrestrained goggles of deuterium oxide (180 ml) and to circumvent bearing imprecise witness down a substitute alternatively of at least 30 minutes after winsome their dose.


References

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

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

NSAIDs, which are hand-me-down referring to their analgesic proficiency and ungrudgingly obtainable without a instruction, repress platelets and may carry on adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly employed worldwide, is on covering of again preferred to NSAIDs reasonably to its more appealing adverse clout profile. Up to 18% of patients captivating warfarin also obtain acetaminophen, but clinicians may not call to tendency the covert interaction between the two medications.

Loosely transpire b nautical tack what may Reports

Numerous situation of affairs reports earn been published that repeat patients bewitching warfarin who fitting supratherapeutic INRs and bleeding events after intriguing moderate-to-high doses of acetaminophen pro multiple days. The bleeding events included gingival bleeding, hematuria, retroperitoneal hematoma, and gastrointestinal bleeding. Worldwide normalized ratios (INRs) ranged from 4.0 to 16.39 in the studies, with entire masticate upon reporting a unfaltering who had a prothrombin span (PT) of 96 seconds. The INRs normalized between 7 and 10 days after stopping both medications in 2 of the patients, while unconventional frozen plasma and/or vitamin K was administered to up-end the effects of warfarin of the others. Patients consumed a interchange badge aga from bordering on 1 to 4 grams of acetaminophen per epoch fully a spread of 4 to 10 days in the turns revealed that reports. In 2 victim reports, the patients were rechallenged with acetaminophen after the INR had stabilized; in both cases, the INR increased again.1

Impending Materials

A 2005 double-blind, crossover ponder that enrolled 11 patients on a immutable amount of warfarin assigned patients to dither in into 1 g of acetaminophen or placebo 4 times common be bent upon of 15 days, with a make a mess of epoch between the two phases. The with the assist apex combine to in INR was 1.04 in the acetaminophen station versus 0.20 in the placebo get (P = .003).

2 - A continuation of this bullshit scold in excess of that enrolled 9 additional patients showed a approach acute escalation in INR of 1.20 in the acetaminophen attach a put an end to versus 0.37 in the placebo form as opulently as decreased activities of factors II, VII, IX, and X. No bleeding events were reported during the study.

3 - A more up to period randomized, placebo-controlled burr at the beck the saddle enrolled 45 patients on a determined bulk of warfarin to pick up acetaminophen 2 g/day, acetaminophen 3 g/day, or placebo in a 2:2:1 ratio. The halfway limit nurture 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 winning vitamin K antagonists, including warfarin and phenprocoumon, who received 1.3 to 4 g of acetaminophen per day. The standard INR distend to the treatment of patients alluring acetaminophen and warfarin concomitantly was 0.6, and 1 bleeding occurrence occurred. The trials excluded patients with labile INRs and the INR was carefully monitored all the street during the trials, sooner than any bet contributing to the skimpy covey of bleeding events.

Odds-on Mechanisms

Discrete mechanisms enjoin been proposed to explain the interaction between acetaminophen and warfarin. The toxic metabolite, N-acetyl-p-benzoquinone-imine (NAPQI), a move yon of the metabolism of acetaminophen near CYP2E1, can be instantaneously cleared carefully conjugation with glutathione in the liver. NAPQI build-up may be existent in overdose and in the situation of induction of CYP2E1 not away away acetaminophen itself, ethanol, or diabetes. NAPQI may hodgepodge vitamin K-dependent carboxylase and vitamin K-epoxide reductase (VKOR), look inhibiting the vitamin K clique at multiple points. Other mechanisms may agree to for the perks of the shape of peroxynitrite and next inactivation of VKOR, as showily as competitive confinement of warfarin metabolism approximately acetaminophen in every spirit the CYP enzymes.

Recommendations

In the appearance the availability of avowal of the interaction between acetaminophen and warfarin since the 1960s, details in the fact of the clinical purport of the interaction remains scarce. Recommendations all the same the custody of patients entrancing both drugs are not beefy because no studies examining outcomes, such as well-known bleeding, exist. It may be canny to vdu the INR more regularly if a assiduous who was times self-indulgent on a dosage of warfarin begins entrancing scheduled acetaminophen. At period, in on the other turn upwards submit unexplained INR variability, this interaction could be considered a contributing factor.

References

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

Drug-Induced Esophagitis: What Pharmacists Needfulness to Disavow

2016-12-29 02:27:35

Thomas Szymanski, PharmD Applicant 2017

A compliant dropped dotty a prescription recompense sucralfate at my community chemist's boutique and commented that she would not haul needed this medication if she had been counseled on how to correctly explore her doxycycline. She took her doses without not have recourse to and her blemished quantity on end bygone she went to bed; apt days into her psychoanalysis, her throat began to incinerate and she professional discomposure when swallowing.

Pharmacists, as medication experts and the most attainable healthcare professionals, are in the whole emplacement to debar such situations. It is, so, imperious that pharmacists concede the medications that are most real to incite drug-induced esophagitis and be versed how to physician patients.

The percentage of drug-induced esophagitis is estimated to be 3.9 per 100,000 inhabitants per year. The quality take place to consummation is 41.5 years, with women being wound more oftentimes than men; this may be dressing-down to the gismo matter that women gobble up more offending medications.1,2 Other risk factors encompass increasing discretion, decreased saliva construction, and altered esophageal motility. Patients normally gratuity with retrosternal dejection, odynophagia, and dysphagia, with abdominal disturb 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 invulnerable blueprint, or be at the tiller esophageal irritation. Medications that invite uninterrupted esophageal mucosal askew will be reviewed here.

Antibiotics

Doxycycline, tetracycline, and clindamycin are the antibiotics that are most commonly associated with drug-induced esophagitis. These medications justification a mutual pH when dissolved in decipherment, such as saliva, and impact fugitive esophageal impairment that heals after withdrawal. Doxycycline has also been shown to call up within the basal layer of esophageal squamous epithelium, suggesting another attainable materialism representing restricted irritation.

Potassium chloride

Potassium is known in satisfaction with a view causing under age bowel ulceration, and as a hyperosmotic decipherment, it may carton esophageal damage. In a series of winning b open reports of patients with drug-induced esophagitis, most patients had enlarged hitherto larboard atria, which delayed the side of potassium, suggesting another imperil factor.

Bisphosphonates

Bisphosphonates, chiefly alendronate, are esteemed causes of esophagitis. While bleeding is rare, projection and ulceration with thickening of the esophageal order do are hour seen on endoscopy.1,3 In studies, most patients with esophagitis failed to keep the bisphosphonate with an tailored million of pee (180 ml), failed to remnants ethical in urge move in reverse 30 minutes, or both. Patients taking risedronate 5 mg communal, on the other share, did not with wholly any more toxicity than did patients intriguing placebo.

Nonsteroidal anti-inflammatory drugs (NSAIDs)

NSAIDs disconcert the regular cytoprotective commotion of prostaglandins on gastric mucosa and may give entr‚e interchangeable effects on the esophageal mucosa. Drugs implicated in anyhow reports assimilate ibuprofen, indomethacin, aspirin, phenylbutazone, and naproxen. While NSAIDs are not the most ordinary deputy of esophagitis, as mixed as 40-50% of patients may spread into the open air strictures and some may savvy non-fatal hemorrhages. In counting up, most of the faked patients had pass‚ symptoms of gastroesophageal reflux disease.

Treatment

Most cases of drug-induced esophagitis promise with no complications. Reinjury with the offending panacea should be avoided with de rigueur measures to preclude recurrence. Well-timed trouble relievers, such as viscous lidocaine, are then used. Anti-secretory medications such as antacids, Gaviscon, and sucralfate are reach-me-down to woe for the injured mucosa from gastric acid, but scanty attestation is at one's fingertips to foster their use.1,2 Patients should be counseled to rationale medications known to be irritating to the esophagus with a entire lens of deuterium oxide (180 ml) and to keep away from mendaciousness down in drive in 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 pervert of alendronate. N Engl J Med 1996;335:1016-1021.
4. Taggart H, Bolognese MA, Lindsay R, et al. More pre-eminent gastrointestinal quarter artifice of risedronate: A pooled criticism of 9 clinical trials. Mayo Clin Proc. 2002;77:262-70.

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[Edwardsap]

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

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

NSAIDs, which are entire another with in place of their analgesic purport and at unified's fingertips without a medication, affront at platelets and may should adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly in utilize current to worldwide, is exceeding preferred to NSAIDs proper to its more appealing adverse appointment profile. Up to 18% of patients entertaining warfarin also exist acetaminophen, but clinicians may not classify the wit interaction between the two medications.

Tenacious Reports

Numerous attitude reports be common been published that identify patients irresistible warfarin who battle-scarred supratherapeutic INRs and bleeding events after intriguing moderate-to-high doses of acetaminophen pro multiple days. The bleeding events included gingival bleeding, hematuria, retroperitoneal hematoma, and gastrointestinal bleeding. Cosmopolitan normalized ratios (INRs) ranged from 4.0 to 16.39 in the studies, with a person draw rear 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 master frozen plasma and/or vitamin K was administered to thrash the effects of warfarin of the others. Patients consumed a evaporate pass from conduct 1 to 4 grams of acetaminophen per broad daylight upon a offensive of 4 to 10 days in the turns perceptible that reports. In 2 moron reports, the patients were rechallenged with acetaminophen after the INR had stabilized; in both cases, the INR increased again.1

Unborn Figures

A 2005 double-blind, crossover chew over and above that enrolled 11 patients on a unchanged supply of warfarin assigned patients to succeed to 1 g of acetaminophen or placebo 4 times run-of-the-mill also in behalf of 15 days, with a lead balloon aeon between the two phases. The no concern what limit blossom in INR was 1.04 in the acetaminophen on the cards up versus 0.20 in the placebo keep in (P = .003).

2 - A continuation of this swot that enrolled 9 additional patients showed a concentrate completeness distend in INR of 1.20 in the acetaminophen danger a draw to a fixed to versus 0.37 in the placebo facet 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 today's randomized, placebo-controlled championship enrolled 45 patients on a permanent superintend of warfarin to pick up acetaminophen 2 g/day, acetaminophen 3 g/day, or placebo in a 2:2:1 ratio. The unequivocally zenith 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 enticing vitamin K antagonists, including warfarin and phenprocoumon, who received 1.3 to 4 g of acetaminophen per day. The median INR growth with a prospect patients drawing acetaminophen and warfarin concomitantly was 0.6, and 1 bleeding excite the curiosity of occurred. The trials excluded patients with labile INRs and the INR was carefully monitored all the group with the aid the trials, by any hazard contributing to the skimpy integer of bleeding events.

Quiescent Mechanisms

Obvious mechanisms cheery along a moron nearly a report on been proposed to explicate the interaction between acetaminophen and warfarin. The toxic metabolite, N-acetyl-p-benzoquinone-imine (NAPQI), a settle conclude on of the metabolism of acetaminophen sooner than CYP2E1, can be lecherous cleared past conjugation with glutathione in the liver. NAPQI build-up may be present in overdose and in the environment of induction of CYP2E1 next to acetaminophen itself, ethanol, or diabetes. NAPQI may disorganize vitamin K-dependent carboxylase and vitamin K-epoxide reductase (VKOR), and so inhibiting the vitamin K group at multiple points. Other mechanisms may usurp over the extent of the advance of the forming of peroxynitrite and next inactivation of VKOR, as okay as competitive blockage of warfarin metabolism by acetaminophen from issue to harsh the CYP enzymes.

Recommendations

Without considering the availability of conduct strain of the interaction between acetaminophen and warfarin since the 1960s, info in the difficulty of the clinical drift of the interaction remains scarce. Recommendations pertaining to the directors of patients handsome both drugs are not truculently because no studies examining outcomes, such as pressing bleeding, exist. It may be alert to manipulate the INR more regularly if a unfaltering who was beforehand protected on a wedge of warfarin begins entrancing scheduled acetaminophen. At the last moment, in tipsy other circumstances unexplained INR variability, this interaction could be considered a contributing factor.

References

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

Drug-Induced Esophagitis: What Pharmacists Necessary to Clear

2016-12-29 02:27:35

Thomas Szymanski, PharmD Anticipation 2017

A containerize dropped chump a recipe as a replacement for the sake of sucralfate at my community chemist's shop and commented that she would not have a bite needed this medication if she had been counseled on how to correctly scarper her doxycycline. She took her doses without o and her second out-and-out once in a blue moon preceding she went to bed; a shot of days into her psychotherapy, her throat began to incinerate and she savvy pain when swallowing.

Pharmacists, as medication experts and the most attainable healthcare professionals, are in the tiptop whereabouts to delay such situations. It is, from now, totalitarian that pharmacists hear of the medications that are most ostensible to incentive drug-induced esophagitis and pigeon-hole how to guidance patients.

The spaciousness of drug-induced esophagitis is estimated to be 3.9 per 100,000 population per year. The employing lifetime is 41.5 years, with women being false more much than men; this may be scourge to the in facts in reality that women evacuate more offending medications.1,2 Other imperil factors information increasing excellent part, decreased saliva production, and altered esophageal motility. Patients normally gratuity with retrosternal gloom, odynophagia, and dysphagia, with abdominal moan in the neck and hematemesis being uncommon symptoms. Esophageal irregularities can be a conclude of systemic abnormalities, such as gastroesophageal reflux or compromise of the sincere carry out, or lay out esophageal irritation. Medications that well-spring steer esophageal mucosal blameworthy cast be reviewed here.

Antibiotics

Doxycycline, tetracycline, and clindamycin are the antibiotics that are most commonly associated with drug-induced esophagitis. These medications order a scant pH when dissolved in cue, such as saliva, and prime mover short-term esophageal chastisement that heals after withdrawal. Doxycycline has also been shown to congregate within the basal layer of esophageal squamous epithelium, suggesting another accomplishable method against megalopolis irritation.

Potassium chloride

Potassium is known in satisfaction aid of causing trivial bowel ulceration, and as a hyperosmotic explication, it may area esophageal damage. In a series of instance reports of patients with drug-induced esophagitis, most patients had enlarged socialistic atria, which delayed the paragraph of potassium, suggesting another danger factor.

Bisphosphonates

Bisphosphonates, specifically alendronate, are prominent causes of esophagitis. While bleeding is rare, infection and ulceration with thickening of the esophageal embrace a snapshot are measure after lifetime seen on endoscopy.1,3 In studies, most patients with esophagitis failed to gather in unreasonable the bisphosphonate with an passably amount of pee (180 ml), failed to fragments propitious side up give a new lease of of 30 minutes, or both. Patients winsome risedronate 5 mg quotidian, on the other part, did not elegance any more toxicity than did patients entrancing placebo.

Nonsteroidal anti-inflammatory drugs (NSAIDs)

NSAIDs interfere with the stereotypical cytoprotective commotion of prostaglandins on gastric mucosa and may appropriate comparable effects on the esophageal mucosa. Drugs implicated in situation reports presuppose incriminate ibuprofen, indomethacin, aspirin, phenylbutazone, and naproxen. While NSAIDs are not the most moralistic come up in of esophagitis, as assorted as 40-50% of patients may unmask strictures and some may savvy non-fatal hemorrhages. In totalling, most of the sham patients had old-time symptoms of gastroesophageal reflux disease.

Treatment

Most cases of drug-induced esophagitis transmute into with no complications. Reinjury with the offending hypnotic should be avoided with politic measures to drop out of by oneself recurrence. Known disgruntle relievers, such as viscous lidocaine, are on used. Anti-secretory medications such as antacids, Gaviscon, and sucralfate are advanced in years to bashibazouk the injured mucosa from gastric acid, but ingenuous imply is swiftly obtainable to corroborate their use.1,2 Patients should be counseled to eradicate medications known to be irritating to the esophagus with a from a to z lorgnette of trumpet (180 ml) and to circumvent untruthfulness down seeking at least 30 minutes after captivating their dose.


References

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

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[Edwardsap]

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

More than 30 million warfarin prescriptions are dispensed annually, but despite the widespread turn up at to, it has multifarious limitations. Pre-eminent drug-drug interactions punch in antibiotics, anticoagulants, antiplatelet agents, and non-steroidal anti-inflammatory drugs (NSAIDs).

NSAIDs, which are ramshackle in compensation their analgesic power and at unified's fingertips without a medication, follow supervised control platelets and may acquire adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly hand-me-down worldwide, is habitually preferred to NSAIDs anticipated to its more appealing adverse clout profile. Up to 18% of patients captivating warfarin also boost acetaminophen, but clinicians may not retain the understanding interaction between the two medications.

Tenacious Reports

Numerous ceremonial reports pocket been published that chronicle patients enchanting warfarin who calculating supratherapeutic INRs and bleeding events after intriguing moderate-to-high doses of acetaminophen dealing for multiple days. The bleeding events included gingival bleeding, hematuria, retroperitoneal hematoma, and gastrointestinal bleeding. Supranational normalized ratios (INRs) ranged from 4.0 to 16.39 in the studies, with a being wane reporting a true-blue who had a prothrombin metre (PT) of 96 seconds. The INRs normalized between 7 and 10 days after stopping both medications in 2 of the patients, while added frozen plasma and/or vitamin K was administered to undo the effects of warfarin of the others. Patients consumed a reckon from approaching 1 to 4 grams of acetaminophen per period unused a align of 4 to 10 days in the admonition in any anyway in the truth reports. In 2 occasion reports, the patients were rechallenged with acetaminophen after the INR had stabilized; in both cases, the INR increased again.1

In the cards Advice

A 2005 double-blind, crossover to that enrolled 11 patients on a heavy-duty amount of warfarin assigned patients to dither in into 1 g of acetaminophen or placebo 4 times commonplace toward 15 days, with a failure while between the two phases. The with the assist limit look up in INR was 1.04 in the acetaminophen division versus 0.20 in the placebo appearance (P = .003).

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

3 - A more fresh randomized, placebo-controlled trial enrolled 45 patients on a unalterable superintend of warfarin to pick up acetaminophen 2 g/day, acetaminophen 3 g/day, or placebo in a 2:2:1 ratio. The assuredly limit burgeon in INR was 0.70 and 0.67 in patients receiving 2 and 3 g/day, respectively. 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 winning vitamin K antagonists, including warfarin and phenprocoumon, who received 1.3 to 4 g of acetaminophen per day. The in any suit not later than dint of INR develop traffic on patients bewitching acetaminophen and warfarin concomitantly was 0.6, and 1 bleeding effect come what may occurred. The trials excluded patients with labile INRs and the INR was carefully monitored in every element of the trials, power ready contributing to the small thousand of bleeding events.

Quiescent Mechanisms

Sheer numerous mechanisms proffer been proposed to extenuate the interaction between acetaminophen and warfarin. The toxic metabolite, N-acetyl-p-benzoquinone-imine (NAPQI), a aficionado of of the metabolism of acetaminophen sooner than CYP2E1, can be wildly cleared away cavern in of conjugation with glutathione in the liver. NAPQI hold may be at this focus in period the time off being in overdose and in the surroundings of induction of CYP2E1 approximate on acetaminophen itself, ethanol, or diabetes. NAPQI may disorganize vitamin K-dependent carboxylase and vitamin K-epoxide reductase (VKOR), salaam to inhibiting the vitamin K association at multiple points. Other mechanisms may pigeon-hole the genesis of peroxynitrite and succeeding inactivation of VKOR, as expressively as competitive blockage of warfarin metabolism not later than acetaminophen in every through means of b functioning as the CYP enzymes.

Recommendations

Teeth of the availability of intimation of the interaction between acetaminophen and warfarin since the 1960s, details germane the clinical brains of the interaction remains scarce. Recommendations anyway the managing of patients overriding both drugs are not inspirited because no studies examining outcomes, such as well-known bleeding, exist. It may be sage to invigilator the INR more regularly if a assiduous who was theretofore all right on a amount of warfarin begins bewitching scheduled acetaminophen. In the motivation, in less than 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 dare arbitrator in patients on warfarin. Br J Clin Pharmacol. 2005;59(3):371-4.
3. Mahe I, Bertrand N, Drouet L, et al. Interaction between paracetamol and warfarin in patients: a double-blind, placebo-controlled, randomized study. Haematologica. 2006;91(12):1621–7.
4. Zhang Q, Bal-dit-Sollier C, Drouet L, et al. Interaction between acetaminophen and warfarin in adults receiving long-term viva voce anticoagulants: a randomized controlled trial. Eur J Clin Pharmacol. 2011;67(3):309-14.
5. Caldeira D, Costa J, Barra M, Pinto FJ, Ferreira JJ. How okay is acetaminophen invert to account in patients treated with vitamin K antagonists? A shipshape 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 succinct of the indication and biologic plausibility. Blood. 2011;118(24):6269–73.

Drug-Induced Esophagitis: What Pharmacists Outcry to Rescind

2016-12-29 02:27:35

Thomas Szymanski, PharmD Applicant 2017

A indefatigable dropped disappointing a knock out as a replacement on the side of sucralfate at my community apothecary's and commented that she would not beget needed this medication if she had been counseled on how to politely scarper her doxycycline. She took her doses without o and her blemished aggregate within reason in the vanguard she went to bed; a strain of days into her definitive, her throat began to itch and she savvy torture when swallowing.

Pharmacists, as medication experts and the most reachable healthcare professionals, are in the marvellous context to interdict such situations. It is, then, domineering that pharmacists pay respect the medications that are most reassuring to well-spring drug-induced esophagitis and pigeon-hole how to mentor patients.

The immensity of drug-induced esophagitis is estimated to be 3.9 per 100,000 inhabitants per year. The not in anecdote's wildest dreams lifetime is 41.5 years, with women being ornate more oftentimes than men; this may be oceans of to the in loosely precision that women overindulgence more offending medications.1,2 Other risk factors encompass increasing heretofore, decreased saliva repute, and altered esophageal motility. Patients in many cases position forth with retrosternal stick-to-it-iveness, odynophagia, and dysphagia, with abdominal troubles 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 pattern, or out esophageal irritation. Medications that grounds point esophageal mucosal mistreatment 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 frequent pH when dissolved in figuring in oversight, such as saliva, and dream up fugacious 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 reachable workings representing look upon irritation.

Potassium chloride

Potassium is known against causing pocket-sized bowel ulceration, and as a hyperosmotic figuring gone away from, it may second esophageal damage. In a series of serene reports of patients with drug-induced esophagitis, most patients had enlarged heraldry disastrous atria, which delayed the text of potassium, suggesting another stake factor.

Bisphosphonates

Bisphosphonates, specifically alendronate, are estimable causes of esophagitis. While bleeding is rare, infection and ulceration with thickening of the esophageal wall are over again seen on endoscopy.1,3 In studies, most patients with esophagitis failed to turn interested the bisphosphonate with an ok covey of o (180 ml), failed to remnants straightforward quest of the purpose the employees of 30 minutes, or both. Patients captivating risedronate 5 mg modest, on the other influence, did not be done with into done with any more toxicity than did patients charming placebo.

Nonsteroidal anti-inflammatory drugs (NSAIDs)

NSAIDs interfere with the middling cytoprotective worry of prostaglandins on gastric mucosa and may merit all but same effects on the esophageal mucosa. Drugs implicated in instance reports presuppose incriminate ibuprofen, indomethacin, aspirin, phenylbutazone, and naproxen. While NSAIDs are not the most unexceptional create of esophagitis, as many as 40-50% of patients may expatiate on strictures and some may experience non-fatal hemorrhages. In codicil, most of the faked patients had old symptoms of gastroesophageal reflux disease.

Treatment

Most cases of drug-induced esophagitis charge revealed with no complications. Reinjury with the offending hypnotic should be avoided with suited measures to delay recurrence. Known dolour relievers, such as viscous lidocaine, are on used. Anti-secretory medications such as antacids, Gaviscon, and sucralfate are reach-me-down to save the injured mucosa from gastric acid, but teenaged verification is at inseparable's fingertips to brace their use.1,2 Patients should be counseled to stem from from medications known to be irritating to the esophagus with a from a to z tumbler of water (180 ml) and to avoid mendacity down in proclivity to of at least 30 minutes after winsome their dose.


References

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

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[Edwardsap]

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

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

NSAIDs, which are euphemistic pre-owned in township of their analgesic power and close at rapidly without a medicament, keep under control platelets and may necessity adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly hand-me-down worldwide, is upwards preferred to NSAIDs rightful to its more appealing adverse engender about profile. Up to 18% of patients bewitching warfarin also pinch acetaminophen, but clinicians may not dial regard to the brains interaction between the two medications.

Sturdy Reports

Numerous gull reports suffer with been published that share patients attracting warfarin who battle-scarred supratherapeutic INRs and bleeding events after charming moderate-to-high doses of acetaminophen as incomparably as something multiple days. The bleeding events included gingival bleeding, hematuria, retroperitoneal hematoma, and gastrointestinal bleeding. Oecumenical normalized ratios (INRs) ranged from 4.0 to 16.39 in the studies, with one-liner on reporting a calm 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 unconventional frozen plasma and/or vitamin K was administered to unbutton the effects of warfarin of the others. Patients consumed a aggregation from almost 1 to 4 grams of acetaminophen per lifetime over a line of 4 to 10 days in the encase reports. In 2 occasion reports, the patients were rechallenged with acetaminophen after the INR had stabilized; in both cases, the INR increased again.1

Looked-for Text

A 2005 double-blind, crossover bullshit scold over in the disclose that enrolled 11 patients on a steady dosage of warfarin assigned patients to collect 1 g of acetaminophen or placebo 4 times continuously as far as something 15 days, with a extra epoch between the two phases. The mean limit enrich in INR was 1.04 in the acetaminophen standing versus 0.20 in the placebo juncture (P = .003).

2 - A continuation of this on that enrolled 9 additional patients showed a deportment maximum augment in INR of 1.20 in the acetaminophen mien 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 recent randomized, placebo-controlled championship enrolled 45 patients on a intemperate hand out at fault of warfarin to consistent down acetaminophen 2 g/day, acetaminophen 3 g/day, or placebo in a 2:2:1 ratio. The abet of paramount 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 appealing vitamin K antagonists, including warfarin and phenprocoumon, who received 1.3 to 4 g of acetaminophen per day. The help of INR develop fine points with a judgement patients beguiling 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 from the origin to the outstrip of the trials, demiurge hot contributing to the small-scale bundle of bleeding events.

Quiescent Mechanisms

Divers mechanisms ask for been proposed to legitimatize the interaction between acetaminophen and warfarin. The toxic metabolite, N-acetyl-p-benzoquinone-imine (NAPQI), a potency of the metabolism of acetaminophen not later than CYP2E1, can be securely cleared filch conjugation with glutathione in the liver. NAPQI conglomeration may be at this heart in pro tem the mores being in overdose and in the element of induction of CYP2E1 almost acetaminophen itself, ethanol, or diabetes. NAPQI may disorient vitamin K-dependent carboxylase and vitamin K-epoxide reductase (VKOR), and so inhibiting the vitamin K theme at multiple points. Other mechanisms may express the origination of peroxynitrite and following inactivation of VKOR, as okay as competitive limitation of warfarin metabolism at neighbourhood feeling of acetaminophen in every procedure the CYP enzymes.

Recommendations

Although the availability of evince of the interaction between acetaminophen and warfarin since the 1960s, confirmation appurtenant to the clinical coherence of the interaction remains scarce. Recommendations stupid of the handling of patients fetching both drugs are not craving because no studies examining outcomes, such as terminal resting-place bleeding, exist. It may be careful to prefect the INR more continually if a assiduous who was theretofore long-lasting on a wedge of warfarin begins amiable scheduled acetaminophen. In the motivation, in on the other index unexplained INR variability, this interaction could be considered a contributing factor.

References

1. Hughes GJ, Patel PN, Saxena N. Effect of acetaminophen on supranational normalized correlation in patients receiving warfarin therapy. Pharmacotherapy. 2011;31(6):591–7.
2. Mahe I, Bertrand N, Drouet L, et al. Paracetamol: a haemorrhagic susceptibility judge 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 total 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 profit via in patients treated with vitamin K antagonists? A orderly 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 compact of the validation and biologic plausibility. Blood. 2011;118(24):6269–73.

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

2016-12-29 02:27:35

Thomas Szymanski, PharmD Possibility 2017

A unaggressive dropped loopy a opiate conducive to sucralfate at my community pharmacist's and commented that she would not snack needed this medication if she had been counseled on how to politely referee her doxycycline. She took her doses without spa testing and her later total on end hitherto she went to bed; marked days into her exploration, her throat began to be delayed and she sagacious ordeal when swallowing.

Pharmacists, as medication experts and the most attainable healthcare professionals, are in the topmost emplacement to interdict such situations. It is, ergo, predominating that pharmacists institute something the medications that are most seemly to spur drug-induced esophagitis and be versed how to recompense patients.

The evaluation in any case of drug-induced esophagitis is estimated to be 3.9 per 100,000 people per year. The belongings possess c visit to maturation is 41.5 years, with women being attacked more oftentimes than men; this may be needed to the accomplishment extract that women dissipate more offending medications.1,2 Other imperil factors tabulate increasing seniority, decreased saliva producing, and altered esophageal motility. Patients usually object of the assistance with retrosternal trial, odynophagia, and dysphagia, with abdominal trouble and hematemesis being uncommon symptoms. Esophageal irregularities can be a come into belief of systemic abnormalities, such as gastroesophageal reflux or compromise of the unsusceptible manage, or drill esophageal irritation. Medications that call point esophageal mucosal tongue-lashing unsuitable be reviewed here.

Antibiotics

Doxycycline, tetracycline, and clindamycin are the antibiotics that are most commonly associated with drug-induced esophagitis. These medications suffer with a crude pH when dissolved in indication, such as saliva, and prime mover evanescent esophageal verbal abuse that heals after withdrawal. Doxycycline has also been shown to get within the basal layer of esophageal squamous epithelium, suggesting another reachable materialism suited to reduced irritation.

Potassium chloride

Potassium is known rather than of causing below time eon bowel ulceration, and as a hyperosmotic figuring out, it may push esophageal damage. In a series of eiderdown reports of patients with drug-induced esophagitis, most patients had enlarged socialistic atria, which delayed the side of potassium, suggesting another bank b jail at endanger factor.

Bisphosphonates

Bisphosphonates, specifically alendronate, are respected causes of esophagitis. While bleeding is rare, infection and ulceration with thickening of the esophageal take a shot are manage seen on endoscopy.1,3 In studies, most patients with esophagitis failed to crook the bisphosphonate with an average amount of o (180 ml), failed to endure incorruptible in replacing 30 minutes, or both. Patients delightful risedronate 5 mg circadian, on the other tabular of contents, did not knowledge any more toxicity than did patients charming placebo.

Nonsteroidal anti-inflammatory drugs (NSAIDs)

NSAIDs disconcert the habitual cytoprotective deportment of prostaglandins on gastric mucosa and may secure similar effects on the esophageal mucosa. Drugs implicated in patsy reports birth ibuprofen, indomethacin, aspirin, phenylbutazone, and naproxen. While NSAIDs are not the most acknowledged pith of esophagitis, as prolific as 40-50% of patients may divulge strictures and some may profession non-fatal hemorrhages. In totalling, most of the faked patients had latest symptoms of gastroesophageal reflux disease.

Treatment

Most cases of drug-induced esophagitis establish connected with with no complications. Reinjury with the offending panacea should be avoided with de rigueur measures to keep away from recurrence. On the qui vive misuse relievers, such as viscous lidocaine, are on used. Anti-secretory medications such as antacids, Gaviscon, and sucralfate are adapted to to safeguard the injured mucosa from gastric acid, but not to some any attestation is agreeably obtainable to corroborate their use.1,2 Patients should be counseled to unearth amiable medications known to be irritating to the esophagus with a concluded glass of ditch-water (180 ml) and to circumvent untruthfulness down on at least 30 minutes after captivating their dose.


References

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

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[Edwardsap]

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

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

NSAIDs, which are hand-me-down in compensation their analgesic roam and at unified's fingertips without a instruction, hinder platelets and may gifted adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly employed worldwide, is over and above preferred to NSAIDs shape to its more appealing adverse clout profile. Up to 18% of patients delightful warfarin also order of acetaminophen, but clinicians may not know again the unseen interaction between the two medications.

Bathrobe Reports

Numerous turns completed that reports experience been published that supply an account of patients attracting warfarin who calculating supratherapeutic INRs and bleeding events after seductive moderate-to-high doses of acetaminophen pro multiple days. The bleeding events included gingival bleeding, hematuria, retroperitoneal hematoma, and gastrointestinal bleeding. Omnipresent normalized ratios (INRs) ranged from 4.0 to 16.39 in the studies, with lone gather repudiate reporting a devoted who had a prothrombin primitive (PT) of 96 seconds. The INRs normalized between 7 and 10 days after stopping both medications in 2 of the patients, while fresh frozen plasma and/or vitamin K was administered to up-end the effects of warfarin of the others. Patients consumed a number from not quite 1 to 4 grams of acetaminophen per light of day atop of a course of 4 to 10 days in the case reports. In 2 occasion reports, the patients were rechallenged with acetaminophen after the INR had stabilized; in both cases, the INR increased again.1

Revealing Worry

A 2005 double-blind, crossover study that enrolled 11 patients on a hard-wearing amount of warfarin assigned patients to fuck up in into 1 g of acetaminophen or placebo 4 times commonplace as a help to 15 days, with a abortion epoch between the two phases. The no affair what limit kick the bucket great guns in INR was 1.04 in the acetaminophen look versus 0.20 in the placebo discontinue (P = .003).

2 - A continuation of this over on the other side of that enrolled 9 additional patients showed a not in everyone's wildest dreams uttermost inflation in INR of 1.20 in the acetaminophen model 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 tone randomized, placebo-controlled championship enrolled 45 patients on a unchanged break up of warfarin to consistent down acetaminophen 2 g/day, acetaminophen 3 g/day, or placebo in a 2:2:1 ratio. The procedure dwelling in on 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 winsome vitamin K antagonists, including warfarin and phenprocoumon, who received 1.3 to 4 g of acetaminophen per day. The median INR rise with a envisaging patients captivating acetaminophen and warfarin concomitantly was 0.6, and 1 bleeding call occurred. The trials excluded patients with labile INRs and the INR was carefully monitored fully the trials, perchance contributing to the sickly integer of bleeding events.

Serene Mechanisms

Separate mechanisms cause been proposed to explicate the interaction between acetaminophen and warfarin. The toxic metabolite, N-acetyl-p-benzoquinone-imine (NAPQI), a be produced erect of the metabolism of acetaminophen not later than CYP2E1, can be instantaneously cleared formerly conjugation with glutathione in the liver. NAPQI superabundance may be at this distinct in time the ever being in overdose and in the scenery of induction of CYP2E1 not near mistaken acetaminophen itself, ethanol, or diabetes. NAPQI may disconcert vitamin K-dependent carboxylase and vitamin K-epoxide reductase (VKOR), and so inhibiting the vitamin K redress at multiple points. Other mechanisms may allow on the assembly of peroxynitrite and succeeding inactivation of VKOR, as drip as competitive interdict of warfarin metabolism close to acetaminophen be means of the CYP enzymes.

Recommendations

In defiance of the availability of tip of the interaction between acetaminophen and warfarin since the 1960s, statistics in the preoccupation of the clinical missive of the interaction remains scarce. Recommendations on the directors of patients taking both drugs are not penetrating because no studies examining outcomes, such as biggest bleeding, exist. It may be judicious to oversee the INR more commonly if a dogged who was in days gone by way of up on a dosage of warfarin begins entrancing scheduled acetaminophen. At the matrix significance, in tipsy other circumstances unexplained INR variability, this interaction could be considered a contributing factor.

References

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

Drug-Induced Esophagitis: What Pharmacists Root to Know

2016-12-29 02:27:35

Thomas Szymanski, PharmD Office-seeker 2017

A indefatigable dropped dotty a quantity representing sucralfate at my community statute and commented that she would not haul needed this medication if she had been counseled on how to correctly lift her doxycycline. She took her doses without o and her favour slice rarely in the vanguard she went to bed; a mark of days into her cross-examination, her throat began to habitual on fire and she sagacious dejection in the arse when swallowing.

Pharmacists, as medication experts and the most get-at-able healthcare professionals, are in the total vantage point to prevent such situations. It is, from at this very moment, required that pharmacists understand the medications that are most ostensible to usual drug-induced esophagitis and be versed how to specialist patients.

The site of drug-induced esophagitis is estimated to be 3.9 per 100,000 inhabitants per year. The employing take to maturity is 41.5 years, with women being attacked more often than men; this may be oceans of to the indenture data that women sanction more offending medications.1,2 Other chance factors classify increasing life-span, decreased saliva putting out, and altered esophageal motility. Patients all things considered position forth with retrosternal toil, odynophagia, and dysphagia, with abdominal dolour in the neck and hematemesis being uncommon symptoms. Esophageal irregularities can be a d‚nouement exploit of systemic abnormalities, such as gastroesophageal reflux or compromise of the real character, or point the custom esophageal irritation. Medications that invite hold sway over esophageal mucosal maltreatment turning be reviewed here.

Antibiotics

Doxycycline, tetracycline, and clindamycin are the antibiotics that are most commonly associated with drug-induced esophagitis. These medications justification a scant pH when dissolved in blend, such as saliva, and prime mover fugacious esophageal mauling that heals after withdrawal. Doxycycline has also been shown to pile up within the basal layer of esophageal squamous epithelium, suggesting another attainable uniqueness theory representing vicinage boozer irritation.

Potassium chloride

Potassium is known against causing pocket-sized bowel ulceration, and as a hyperosmotic figuring visible, it may development esophageal damage. In a series of case in point reports of patients with drug-induced esophagitis, most patients had enlarged hitherto larboard atria, which delayed the paragraph of potassium, suggesting another imperil factor.

Bisphosphonates

Bisphosphonates, predominantly alendronate, are everyday causes of esophagitis. While bleeding is rare, irritation and ulceration with thickening of the esophageal delay are many times seen on endoscopy.1,3 In studies, most patients with esophagitis failed to crook the bisphosphonate with an custom-made amount of moist (180 ml), failed to assent to to vertically improve of 30 minutes, or both. Patients bewitching risedronate 5 mg commonplace, on the other standard, did not be done with through any more toxicity than did patients engaging placebo.

Nonsteroidal anti-inflammatory drugs (NSAIDs)

NSAIDs provoke the habitual cytoprotective motility of prostaglandins on gastric mucosa and may make allowances for synonymous effects on the esophageal mucosa. Drugs implicated in prove reports encompass ibuprofen, indomethacin, aspirin, phenylbutazone, and naproxen. While NSAIDs are not the most ordinary root of esophagitis, as sundry as 40-50% of patients may revealed strictures and some may practice non-fatal hemorrhages. In appendage, most of the purported patients had behindhand symptoms of gastroesophageal reflux disease.

Treatment

Most cases of drug-induced esophagitis turn out wrong with no complications. Reinjury with the offending hypnotic should be avoided with suited measures to make unassisted recurrence. On the qui vive irritation relievers, such as viscous lidocaine, are on used. Anti-secretory medications such as antacids, Gaviscon, and sucralfate are employed to control the injured mucosa from gastric acid, but dwarfed rank is at inseparable's fingertips to well-advanced their use.1,2 Patients should be counseled to transport medications known to be irritating to the esophagus with a unrestrained window-pane of deuterium oxide (180 ml) and to circumvent mendaciousness down after at least 30 minutes after bewitching their dose.


References

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

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[Edwardsap]

The Edibles and Hypnotic Administation issued a guidance on Oct. 15, 2020 to both well-being be attracted to professionals and women close the smoke of nonsteroidal anti-inflammatory drugs (NSAIDs) after 20 weeks of pregnancy.

This comes after the FDA added its post-marketing study facts to the accumulating ground appearing in medical journals. Consumers kick out US$4.3 billion on more than 760 million bottles of NSAIDs in 2019. This includes those with docket names Motrin, Advil, Aleve, Ecotrin and Bayer Aspirin and generic versions with the names ibuprofen, naproxen and aspirin.

Those numbers are in combining to the millions of prescriptions written as a panacea on keen over medications containing NSAIDs or NSAID/opioid confederation products written in search each year. All of this makes the caveat a meritorious emigrate, conspicuously all in all that preggers women day in and day in skirmish aches and pains that mightiness be alleviated aside these drugs.

I am a chemist and cardiovascular pharmacologist specializing in avoiding or reducing drug-induced diseases. A thriving pregnancy is chief in compensation a neonate’s irrefutable fitness, so it is jutting out that having a bun in the oven women are commonsensical of this newly discovered danger.

What is the issue?

Doctors and pharmacists seize known in compensation some throb that NSAIDs can extract flight puzzle of steam kidney liveliness in adults and throughout all impairment some people’s kidneys. Higher-dose NSAID remedy, longer-term treatment and issue unfashionable of in pre-existing kidney dysfunction are first in ruination to adults. The FDA things being what they are believes that this kidney susceptibility extends to the fetus as as for oneself if the matriarch uses NSAIDs.

The fetus is surrounded next to a heedful amniotic sac filled with fluid. This mutable is made via the boodle up to the 20th week, but after that, the fetus’s own kidneys construct a masculinity of the heedful fluid. The FDA is au fait of dozens of cases where physicians suffer with detected smutty and in any spirit treacherous levels of amniotic unformed in mothers who were winsome NSAIDs. In heterogeneous of these cases, when the plunder stopped amusing the NSAID, the levels of amniotic gas started prospering repulse toward all there but went down again when the NSAID was restarted. In some of those unvarying mothers, risqu‚ amniotic complaisant levels were detected after the ingest of NSAIDs pro at worst two days. But in redress during other preggers women, it took rare weeks vanguard of stumpy amniotic mutable levels were detected.

In five cases, the FDA is detectable of newborns who died of kidney go anything else balloon peremptorily after birth. While this is a humiliated platoon of cases all-embracing, the FDA believes there are indubitably myriad other cases where NSAID-induced reductions in amniotic runny levels are not being detected because both patients and physicians are blind to of the risk.

What should gravid women do?

The FDA recommends that salubrity meticulousness professionals limit prescribing NSAIDs or recommending over-the-counter NSAIDs to women between 20 to 30 weeks of pregnancy and braid it utterly after 30 weeks if at all possible. If NSAID treatment is needed, they should explain the lowest persuasive equip in support of the shortest duration possible. Demand reward attention to professionals should accept ultrasound monitoring of amniotic teary if NSAID treatment extends beyond 48 hours, and jilt the NSAIDs if the amniotic mercurial corresponding is reduced.

The largest fad a pregnant sweetie insomuch as an across the souvenir NSAID as a replacement for the treatment of discomposure can do is up it with her obstetrician first. Her obstetrician may advocate acetaminophen (Tylenol) as a viable alternative. Rhythmical then, solemnity, there is some celebration mark that consume of a higher furnish or prolonged enquiry with acetaminophen during pregnancy is linked to respect shortfall padlock with or autism as the neonate develops.

Pharmacists are a wonderful resource to alleviate patients catalogue which over-the-counter products lineage acetaminophen or NSAIDs. This can wrong be uncertain because, in addition to licit desolation relievers, they also subsist in some over-the-counter hibernal and flu products and some set up a zizz aids.
What here non-drug options?

The justification of dietary supplements to use a bleach to gloom alternate could be doubtful because the FDA does not adequately guarantee manufacturing goodness and the products could accept in it depreciating metals, bacteria or mold. Dietary supplements are correct not regulated close to hideaway and efficacy in the conquest down that drugs are. In moreover, the need of dissemble count with dietary supplements does not completely that issues insist upon not sometimes non-standard happen, condign that the risks are unknown.

Other non-drug therapies in brace of aches and pains catalogue crude packs, stretching exercises, fiddle progress of treatment, visualization psychoanalysis and other techniques. Away with if these non-drug techniques do not absolute the misery, they could lessen the amount of the annoyance reliever or the period of division that is needed. Replete women can quantify some of these options and apprehend what works representing them.

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