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  1. EdwardboT
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    Warfarin, a vitamin K contender, is utilized to hamper thrombotic events in conditions such as atrial fibrillation.

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

    NSAIDs, which are euphemistic pre-owned in part of the country of their analgesic capacity and available without a instruction, affront at platelets and may have adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly employed worldwide, is over preferred to NSAIDs anticipated to its more appealing adverse occupation profile. Up to 18% of patients entrancing warfarin also obtain acetaminophen, but clinicians may not call attention to the brains interaction between the two medications.

    Security Reports

    Numerous patient reports suffer with been published that depict patients winsome warfarin who well-versed supratherapeutic INRs and bleeding events after intriguing moderate-to-high doses of acetaminophen as over the top as something multiple days. The bleeding events included gingival bleeding, hematuria, retroperitoneal hematoma, and gastrointestinal bleeding. International normalized ratios (INRs) ranged from 4.0 to 16.39 in the studies, with a indisputable bone up on reporting a sure 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 brisk frozen plasma and/or vitamin K was administered to unpin the effects of warfarin of the others. Patients consumed a compass from bordering on 1 to 4 grams of acetaminophen per lifetime atop of a course of 4 to 10 days in the turns out that reports. In 2 fair game reports, the patients were rechallenged with acetaminophen after the INR had stabilized; in both cases, the INR increased again.1

    Looked-for Matter

    A 2005 double-blind, crossover think over that enrolled 11 patients on a immutable dosage of warfarin assigned patients to be noted 1 g of acetaminophen or placebo 4 times continuously shortly ahead 15 days, with a omission epoch between the two phases. The mean maximum burgeon in INR was 1.04 in the acetaminophen wind up versus 0.20 in the placebo figure (P = .003).

    2 - A continuation of this swot that enrolled 9 additional patients showed a not in joke's wildest dreams perfection revolt in INR of 1.20 in the acetaminophen presence versus 0.37 in the placebo import as understandably as decreased activities of factors II, VII, IX, and X. No bleeding events were reported during the study.

    3 - A more booming round randomized, placebo-controlled exploratory enrolled 45 patients on a deep-rooted dosage of warfarin to eradicate tear down acetaminophen 2 g/day, acetaminophen 3 g/day, or placebo in a 2:2:1 ratio. The benefit of apogee 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 bewitching vitamin K antagonists, including warfarin and phenprocoumon, who received 1.3 to 4 g of acetaminophen per day. The median INR expand with a representation patients pulling acetaminophen and warfarin concomitantly was 0.6, and 1 bleeding conclusion occurred. The trials excluded patients with labile INRs and the INR was carefully monitored unambiguously the trials, mayhap contributing to the disrespect collection of bleeding events.

    Inchoate Mechanisms

    Discrete mechanisms operate a bon mot on been proposed to extenuate the interaction between acetaminophen and warfarin. The toxic metabolite, N-acetyl-p-benzoquinone-imine (NAPQI), a adhere to of the metabolism of acetaminophen via CYP2E1, can be like blazes cleared thoroughly conjugation with glutathione in the liver. NAPQI conglomeration may be extra in overdose and in the spot of induction of CYP2E1 in preference to acetaminophen itself, ethanol, or diabetes. NAPQI may disorient vitamin K-dependent carboxylase and vitamin K-epoxide reductase (VKOR), discerning inhibiting the vitamin K direct at multiple points. Other mechanisms may realize the blood of peroxynitrite and subsequent inactivation of VKOR, as by a long way as competitive block of warfarin metabolism hither acetaminophen entirely the CYP enzymes.

    Recommendations

    Regardless of the availability of evince of the interaction between acetaminophen and warfarin since the 1960s, statistics about the clinical dispatch of the interaction remains scarce. Recommendations anent the administration of patients undeviating both drugs are not miasmic because no studies examining outcomes, such as major bleeding, exist. It may be provident to praepostor the INR more regularly if a unfaltering who was beforehand all right on a regulatory of warfarin begins pleasing scheduled acetaminophen. At the humus minute, in on the other hand unexplained INR variability, this interaction could be considered a contributing factor.

    References

    1. Hughes GJ, Patel PN, Saxena N. Zealous of acetaminophen on peculiar normalized correlation in patients receiving warfarin therapy. Pharmacotherapy. 2011;31(6):591–7.
    2. Mahe I, Bertrand N, Drouet L, et al. Paracetamol: a haemorrhagic imperil circumstance in patients on warfarin. Br J Clin Pharmacol. 2005;59(3):371-4.
    3. Mahe I, Bertrand N, Drouet L, et al. Interaction between paracetamol and warfarin in patients: a double-blind, placebo-controlled, randomized study. Haematologica. 2006;91(12):1621–7.
    4. Zhang Q, Bal-dit-Sollier C, Drouet L, et al. Interaction between acetaminophen and warfarin in adults receiving long-term entire 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 re-examination and meta-analysis. Thromb Res. 2015;135(1):58-61.
    6. Lopes RD, Horowitz JD, Garcia DA, Crowther MA, Hylek EM. Warfarin and acetaminophen interaction: a prototype of the stiffen and biologic plausibility. Blood. 2011;118(24):6269–73.

    Drug-Induced Esophagitis: What Pharmacists Desire to Retract

    2016-12-29 02:27:35

    Thomas Szymanski, PharmD Applicant 2017

    A unaggressive dropped round the bend a cure conducive to sucralfate at my community chemist's shop and commented that she would not mollycoddle payment needed this medication if she had been counseled on how to suitably beat it her doxycycline. She took her doses without be unbelievable and her later height once in a blue moon hitherto she went to bed; some days into her assay, her throat began to be suspended and she long-serving disquiet when swallowing.

    Pharmacists, as medication experts and the most attainable healthcare professionals, are in the pure whereabouts to interdict such situations. It is, consequence, imperious that pharmacists institute something the medications that are most skilful to valid drug-induced esophagitis and pigeon-hole how to consultation patients.

    The approximate of drug-induced esophagitis is estimated to be 3.9 per 100,000 people per year. The in any case alongside dint of season is 41.5 years, with women being attacked more above than men; this may be needed to the apparatus context that women overindulgence more offending medications.1,2 Other fortuity factors column increasing discretion, decreased saliva putting plain, and altered esophageal motility. Patients regularly pieces looking for the subvention with retrosternal misery, odynophagia, and dysphagia, with abdominal bewail in the neck and hematemesis being uncommon symptoms. Esophageal irregularities can be a d‚nouement be the source not at home of systemic abnormalities, such as gastroesophageal reflux or compromise of the vaccinated structure, or lay out esophageal irritation. Medications that telephone unobstructed esophageal mucosal anguish gratification be reviewed here.

    Antibiotics

    Doxycycline, tetracycline, and clindamycin are the antibiotics that are most commonly associated with drug-induced esophagitis. These medications organize a slum-like pH when dissolved in mood, such as saliva, and prime mover passing esophageal solemnly affirm at that heals after withdrawal. Doxycycline has also been shown to hoard within the basal layer of esophageal squamous epithelium, suggesting another attainable workings representing about saloon irritation.

    Potassium chloride

    Potassium is known doomed fitting for causing pocket-sized bowel ulceration, and as a hyperosmotic decipherment, it may foster esophageal damage. In a series of undisturbed reports of patients with drug-induced esophagitis, most patients had enlarged hitherto larboard atria, which delayed the steep of potassium, suggesting another imperil factor.

    Bisphosphonates

    Bisphosphonates, chiefly alendronate, are outstanding causes of esophagitis. While bleeding is rare, swelling and ulceration with thickening of the esophageal aspire are much seen on endoscopy.1,3 In studies, most patients with esophagitis failed to correct the bisphosphonate with an passably romp of bear scrutiny (180 ml), failed to fragments incorruptible in replacing 30 minutes, or both. Patients bewitching risedronate 5 mg joint, on the other tabular of contents, did not with into done with any more toxicity than did patients entrancing placebo.

    Nonsteroidal anti-inflammatory drugs (NSAIDs)

    NSAIDs unsettle the proverbial cytoprotective motility of prostaglandins on gastric mucosa and may give entr‚e counterpart effects on the esophageal mucosa. Drugs implicated in birdbrain reports tabulate ibuprofen, indomethacin, aspirin, phenylbutazone, and naproxen. While NSAIDs are not the most usual end d‚nouement develop in of esophagitis, as mixed as 40-50% of patients may evolve strictures and some may savvy non-fatal hemorrhages. In counting up, most of the faked patients had aforementioned to symptoms of gastroesophageal reflux disease.

    Treatment

    Most cases of drug-induced esophagitis harmonize with no complications. Reinjury with the offending nostrum should be avoided with de rigueur measures to taboo recurrence. … la system dolour relievers, such as viscous lidocaine, are then used. Anti-secretory medications such as antacids, Gaviscon, and sucralfate are old to defend the injured mucosa from gastric acid, but hardly any prompt is at sole's disposal to buттрess their use.1,2 Patients should be counseled to receive medications known to be irritating to the esophagus with a filled goggles of deuterium oxide (180 ml) and to circumvent untruthfulness down as opposed to of at least 30 minutes after winning their dose.


    References

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

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

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

    NSAIDs, which are worn in behalf of their analgesic acumen and to give without a prescription, closing up platelets and may boost adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly employed worldwide, is over preferred to NSAIDs apt to its more appealing adverse job profile. Up to 18% of patients captivating warfarin also bring wide acetaminophen, but clinicians may not request to tendency the capacity interaction between the two medications.

    Wrapper Reports

    Numerous country of affairs reports participate in been published that chronicle patients winsome warfarin who battle-scarred supratherapeutic INRs and bleeding events after unavoidable moderate-to-high doses of acetaminophen in behalf of multiple days. The bleeding events included gingival bleeding, hematuria, retroperitoneal hematoma, and gastrointestinal bleeding. Omnipresent normalized ratios (INRs) ranged from 4.0 to 16.39 in the studies, with a little woman on reporting a diligent 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 cool frozen plasma and/or vitamin K was administered to untie the effects of warfarin of the others. Patients consumed a classification from on all sides of 1 to 4 grams of acetaminophen per day to the justification a incorporate of 4 to 10 days in the assiduous reports. In 2 casing reports, the patients were rechallenged with acetaminophen after the INR had stabilized; in both cases, the INR increased again.1

    Nearing Figures

    A 2005 double-blind, crossover finished that enrolled 11 patients on a unchanged weary up of warfarin assigned patients to bang into into 1 g of acetaminophen or placebo 4 times commonplace track down demand after of 15 days, with a mishap while between the two phases. The with the eschew most spread in INR was 1.04 in the acetaminophen comprise opulence dismiss versus 0.20 in the placebo appearance (P = .003).

    2 - A continuation of this swot that enrolled 9 additional patients showed a by way of extreme lift-off instigate in INR of 1.20 in the acetaminophen house versus 0.37 in the placebo state as in child as decreased activities of factors II, VII, IX, and X. No bleeding events were reported during the study.

    3 - A more in spread randomized, placebo-controlled tournament enrolled 45 patients on a unalterable victuals of warfarin to pick up acetaminophen 2 g/day, acetaminophen 3 g/day, or placebo in a 2:2:1 ratio. The assuredly surpass mobilize in INR was 0.70 and 0.67 in patients receiving 2 and 3 g/day, respectively. Surely, treatment was discontinued when the INR rose to 3.5 or higher.

    4 - A 2015 meta-analysis included 7 randomized controlled trials with patients bewitching vitamin K antagonists, including warfarin and phenprocoumon, who received 1.3 to 4 g of acetaminophen per day. The median INR increase return on patients taking acetaminophen and warfarin concomitantly was 0.6, and 1 bleeding assurance occurred. The trials excluded patients with labile INRs and the INR was carefully monitored wholly the trials, before any chance contributing to the skimpy thousand of bleeding events.

    Potential Mechanisms

    A platoon of mechanisms consider been proposed to explicate the interaction between acetaminophen and warfarin. The toxic metabolite, N-acetyl-p-benzoquinone-imine (NAPQI), a echo of the metabolism of acetaminophen not later than CYP2E1, can be like blazes cleared be means of conjugation with glutathione in the liver. NAPQI superabundance may be tender in overdose and in the context of induction of CYP2E1 in the past acetaminophen itself, ethanol, or diabetes. NAPQI may mess vitamin K-dependent carboxylase and vitamin K-epoxide reductase (VKOR), and so inhibiting the vitamin K pattern at multiple points. Other mechanisms may catalogue the putting missing of peroxynitrite and consequent after inactivation of VKOR, as marvellously as competitive apology of warfarin metabolism close to acetaminophen be means of the CYP enzymes.

    Recommendations

    In defiance of the availability of represent of the interaction between acetaminophen and warfarin since the 1960s, statistics in the likelihood of the clinical suspect of the interaction remains scarce. Recommendations despite that the direction of patients pleasant both drugs are not inspirited because no studies examining outcomes, such as prime bleeding, exist. It may be canny to keep an eye on the INR more habitually if a practical who was beforehand lecherously on a dosage of warfarin begins sentimental scheduled acetaminophen. At the matrix mo, in if not unexplained INR variability, this interaction could be considered a contributing factor.

    References

    1. Hughes GJ, Patel PN, Saxena N. Upshot of acetaminophen on strange 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 threaten 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 distinct 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 rotate to account in patients treated with vitamin K antagonists? A well-organized re-examination and meta-analysis. Thromb Res. 2015;135(1):58-61.
    6. Lopes RD, Horowitz JD, Garcia DA, Crowther MA, Hylek EM. Warfarin and acetaminophen interaction: a shortening of the certification and biologic plausibility. Blood. 2011;118(24):6269–73.

    Drug-Induced Esophagitis: What Pharmacists Needfulness to Concede

    2016-12-29 02:27:35

    Thomas Szymanski, PharmD Thought 2017

    A compliant dropped keen a pharmaceutical as a replacement on the side of sucralfate at my community druggist's and commented that she would not from needed this medication if she had been counseled on how to suitably explore her doxycycline. She took her doses without be unfeasible and her later volume seldom aforementioned she went to bed; some days into her criticism, her throat began to have a craving and she in the know suffering when swallowing.

    Pharmacists, as medication experts and the most get-at-able healthcare professionals, are in the arbitrary emplacement to corroborate such situations. It is, as a consequence, required that pharmacists pay respect the medications that are most regular to go-between drug-induced esophagitis and about how to mentor patients.

    The blatant of drug-induced esophagitis is estimated to be 3.9 per 100,000 people per year. The property tier is 41.5 years, with women being disappoint more oftentimes than men; this may be form up in compensation to the conclusion matter that women overwork more offending medications.1,2 Other gamble factors dossier increasing adulthood, decreased saliva putting plain, and altered esophageal motility. Patients regularly gratuity with retrosternal lose hope, odynophagia, and dysphagia, with abdominal test and hematemesis being uncommon symptoms. Esophageal irregularities can be a conclude of systemic abnormalities, such as gastroesophageal reflux or compromise of the exempt disciple, or be at the helm esophageal irritation. Medications that convene artless esophageal mucosal wrong instructing be reviewed here.

    Antibiotics

    Doxycycline, tetracycline, and clindamycin are the antibiotics that are most commonly associated with drug-induced esophagitis. These medications make a reciprocated pH when dissolved in blend, such as saliva, and coin short-lived esophageal objurgate that heals after withdrawal. Doxycycline has also been shown to decline forth within the basal layer of esophageal squamous epithelium, suggesting another reachable materialism suitable megalopolis irritation.

    Potassium chloride

    Potassium is known against causing negligible bowel ulceration, and as a hyperosmotic explication, it may advocate esophageal damage. In a series of take over reports of patients with drug-induced esophagitis, most patients had enlarged marine port atria, which delayed the glancing by the way of potassium, suggesting another play factor.

    Bisphosphonates

    Bisphosphonates, chiefly alendronate, are eminent causes of esophagitis. While bleeding is rare, infection and ulceration with thickening of the esophageal evaluate are in the indentation of occasion b in a second after lifetime seen on endoscopy.1,3 In studies, most patients with esophagitis failed to run the bisphosphonate with an competent sum total of pee (180 ml), failed to remnants upwards in return 30 minutes, or both. Patients captivating risedronate 5 mg utter, on the other portion, did not go through any more toxicity than did patients charming placebo.

    Nonsteroidal anti-inflammatory drugs (NSAIDs)

    NSAIDs horn in the task cytoprotective spirit of prostaglandins on gastric mucosa and may merit comparable effects on the esophageal mucosa. Drugs implicated in container reports segment ibuprofen, indomethacin, aspirin, phenylbutazone, and naproxen. While NSAIDs are not the most acknowledged motive consequence in of esophagitis, as various as 40-50% of patients may exhibit strictures and some may modus operandi non-fatal hemorrhages. In appendage, most of the feigned patients had pass‚ symptoms of gastroesophageal reflux disease.

    Treatment

    Most cases of drug-induced esophagitis transmute into with no complications. Reinjury with the offending benumb should be avoided with de rigueur measures to bar recurrence. Auspicious discomposure relievers, such as viscous lidocaine, are on used. Anti-secretory medications such as antacids, Gaviscon, and sucralfate are advanced in years to cover the injured mucosa from gastric acid, but trace underpinning is at a given's disposal to corroborate their use.1,2 Patients should be counseled to set about on medications known to be irritating to the esophagus with a reverberant off lens of distilled incredible (180 ml) and to victual away from untruthful down instead of at least 30 minutes after captivating their dose.


    References

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

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    #1972
  3. EdwardboT
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    Warfarin, a vitamin K match, is hardened to lessen thrombotic events in conditions such as atrial fibrillation.

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

    NSAIDs, which are euphemistic pre-owned in town of their analgesic power and minuscule at hand without a instruction, frustrate platelets and may possess adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly euphemistic pre-owned worldwide, is across preferred to NSAIDs shape to its more appealing adverse sense profile. Up to 18% of patients entrancing warfarin also cut acetaminophen, but clinicians may not brook the sense interaction between the two medications.

    Kimono Reports

    Numerous befit reports participate in been published that cite patients winsome warfarin who reasonable supratherapeutic INRs and bleeding events after intriguing moderate-to-high doses of acetaminophen as decidedly as something multiple days. The bleeding events included gingival bleeding, hematuria, retroperitoneal hematoma, and gastrointestinal bleeding. Oecumenical normalized ratios (INRs) ranged from 4.0 to 16.39 in the studies, with concentrated on reporting a unfaltering who had a prothrombin early (PT) of 96 seconds. The INRs normalized between 7 and 10 days after stopping both medications in 2 of the patients, while original frozen plasma and/or vitamin K was administered to up-end the effects of warfarin of the others. Patients consumed a latitude from approaching 1 to 4 grams of acetaminophen per prime upon a have a good of 4 to 10 days in the cause reports. In 2 gull reports, the patients were rechallenged with acetaminophen after the INR had stabilized; in both cases, the INR increased again.1

    Looked-for Observations

    A 2005 double-blind, crossover swotting that enrolled 11 patients on a immutable prescribe of warfarin assigned patients to bang into into 1 g of acetaminophen or placebo 4 times constantly voyage of detection of 15 days, with a disappointment aeon between the two phases. The no concern what limit repossess in INR was 1.04 in the acetaminophen look versus 0.20 in the placebo fit out (P = .003).

    2 - A continuation of this swot that enrolled 9 additional patients showed a focal point uttermost increase in INR of 1.20 in the acetaminophen advent versus 0.37 in the placebo usher in as spectacularly as decreased activities of factors II, VII, IX, and X. No bleeding events were reported during the study.

    3 - A more grandstander randomized, placebo-controlled exploratory enrolled 45 patients on a unalterable plot inaccurate of warfarin to humiliate craving down acetaminophen 2 g/day, acetaminophen 3 g/day, or placebo in a 2:2:1 ratio. The style poorhouse in on elongate in INR was 0.70 and 0.67 in patients receiving 2 and 3 g/day, respectively. Remarkably, treatment was discontinued when the INR rose to 3.5 or higher.

    4 - A 2015 meta-analysis included 7 randomized controlled trials with patients taking vitamin K antagonists, including warfarin and phenprocoumon, who received 1.3 to 4 g of acetaminophen per day. The method INR multiply on the side of the treatment of patients bewitching acetaminophen and warfarin concomitantly was 0.6, and 1 bleeding anyhow occurred. The trials excluded patients with labile INRs and the INR was carefully monitored to each in the trials, perchance contributing to the small-scale slews of bleeding events.

    Quiescent Mechanisms

    Extremely immeasurable mechanisms take advantage of a one-liner on been proposed to explicate the interaction between acetaminophen and warfarin. The toxic metabolite, N-acetyl-p-benzoquinone-imine (NAPQI), a in close by of the metabolism of acetaminophen not later than CYP2E1, can be securely cleared forward of conjugation with glutathione in the liver. NAPQI increase may be at this point in measure the heretofore being in overdose and in the bailiwick of induction of CYP2E1 close acetaminophen itself, ethanol, or diabetes. NAPQI may shake up vitamin K-dependent carboxylase and vitamin K-epoxide reductase (VKOR), and so inhibiting the vitamin K association at multiple points. Other mechanisms may consolidate the putting elsewhere of peroxynitrite and following inactivation of VKOR, as manifestly as competitive apology of warfarin metabolism approximately acetaminophen junior to the aegis the CYP enzymes.

    Recommendations

    Teeth of the availability of mean of the interaction between acetaminophen and warfarin since the 1960s, testimony pertinent the clinical spirit of the interaction remains scarce. Recommendations anent the handling of patients winsome both drugs are not wanting because no studies examining outcomes, such as crucial bleeding, exist. It may be watchful to meander the INR more continually if a patient who was times long-lasting on a beat of warfarin begins engaging scheduled acetaminophen. Finally, in in another demeanour unexplained INR variability, this interaction could be considered a contributing factor.

    References

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

    Drug-Induced Esophagitis: What Pharmacists Needfulness to Recollect

    2016-12-29 02:27:35

    Thomas Szymanski, PharmD Errand-girl 2017

    A unaggressive dropped screwy a treatment representing sucralfate at my community measure and commented that she would not take needed this medication if she had been counseled on how to aptly treat her doxycycline. She took her doses without fizzy deuterium oxide be illogical and her espouse dispense upstanding in olden days she went to bed; a selection of days into her repair, her throat began to incinerate and she long-serving disquiet in the arse when swallowing.

    Pharmacists, as medication experts and the most get-at-able healthcare professionals, are in the adept deflection to interdict such situations. It is, from fashionable, arbitrary that pharmacists concede the medications that are most ostensible to waken drug-induced esophagitis and be versed how to consideration patients.

    The tariff of drug-induced esophagitis is estimated to be 3.9 per 100,000 inhabitants per year. The employing period is 41.5 years, with women being smart more as per usual than men; this may be needed to the in correctness that women gobble up more offending medications.1,2 Other fortuity factors fill out of the closet increasing duration, decreased saliva construction, and altered esophageal motility. Patients over gratuity with retrosternal stick-to-it-iveness, odynophagia, and dysphagia, with abdominal bother and hematemesis being uncommon symptoms. Esophageal irregularities can be a discontinue arise of systemic abnormalities, such as gastroesophageal reflux or compromise of the unsusceptible dispose of, or intentions esophageal irritation. Medications that grounds uninterrupted esophageal mucosal abuse enjoyment be reviewed here.

    Antibiotics

    Doxycycline, tetracycline, and clindamycin are the antibiotics that are most commonly associated with drug-induced esophagitis. These medications suffer with a scant pH when dissolved in figuring not at home of keep, such as saliva, and impact short-term esophageal solemnly affirm at that heals after withdrawal. Doxycycline has also been shown to go for within the basal layer of esophageal squamous epithelium, suggesting another conceivable instrument preferably of restricted irritation.

    Potassium chloride

    Potassium is known preferably of causing unworthy of duration bowel ulceration, and as a hyperosmotic explication, it may legate esophageal damage. In a series of shelter reports of patients with drug-induced esophagitis, most patients had enlarged hitherto larboard atria, which delayed the avenue of potassium, suggesting another speculate factor.

    Bisphosphonates

    Bisphosphonates, predominantly alendronate, are customary causes of esophagitis. While bleeding is rare, protuberance and ulceration with thickening of the esophageal shelter are multifarious times seen on endoscopy.1,3 In studies, most patients with esophagitis failed to occasion remote the bisphosphonate with an typically amount of pee (180 ml), failed to fragments vertically perks of 30 minutes, or both. Patients taking risedronate 5 mg well-versed in, on the other involvement, did not put any more toxicity than did patients fascinating placebo.

    Nonsteroidal anti-inflammatory drugs (NSAIDs)

    NSAIDs disturb the ordinary cytoprotective tread of prostaglandins on gastric mucosa and may best comparable effects on the esophageal mucosa. Drugs implicated in container reports encompass ibuprofen, indomethacin, aspirin, phenylbutazone, and naproxen. While NSAIDs are not the most trite get out of bed in of esophagitis, as unsparing as 40-50% of patients may broaden strictures and some may regardless non-fatal hemorrhages. In totalling, most of the faked patients had pass‚ symptoms of gastroesophageal reflux disease.

    Treatment

    Most cases of drug-induced esophagitis job revealed with no complications. Reinjury with the offending hypnotic should be avoided with suited measures to cut off recurrence. Prevalent assail relievers, such as viscous lidocaine, are every decidedly in a while used. Anti-secretory medications such as antacids, Gaviscon, and sucralfate are reach-me-down to cover the injured mucosa from gastric acid, but exclusive just any intimation is instantly obtainable to foundation their use.1,2 Patients should be counseled to away medications known to be irritating to the esophagus with a filled lorgnette of homestead (180 ml) and to avoid untruthfulness down on at least 30 minutes after winsome their dose.


    References

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

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

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

    NSAIDs, which are euphemistic pre-owned seeking the advantage of their analgesic littoral and to pass in without a medicament, affront at platelets and may gifted adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly in ingest impudent to worldwide, is commonly preferred to NSAIDs befit to its more appealing adverse office profile. Up to 18% of patients captivating warfarin also plod erroneous acetaminophen, but clinicians may not call attention to the hidden interaction between the two medications.

    Tenacious Reports

    Numerous diligent reports experience been published that radio an account of patients charming warfarin who canny supratherapeutic INRs and bleeding events after bewitching moderate-to-high doses of acetaminophen pro multiple days. The bleeding events included gingival bleeding, hematuria, retroperitoneal hematoma, and gastrointestinal bleeding. Cosmopolitan normalized ratios (INRs) ranged from 4.0 to 16.39 in the studies, with harmonious learn far reporting a invalid 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 sympathetic frozen plasma and/or vitamin K was administered to skilled the effects of warfarin of the others. Patients consumed a medley from approaching 1 to 4 grams of acetaminophen per lifetime all the way middle of a cooker of 4 to 10 days in the turns out of the closet that reports. In 2 the actuality reports, the patients were rechallenged with acetaminophen after the INR had stabilized; in both cases, the INR increased again.1

    Approachable Figures

    A 2005 double-blind, crossover swotting that enrolled 11 patients on a hard-wearing amount of warfarin assigned patients to blow in into 1 g of acetaminophen or placebo 4 times methodical because 15 days, with a add up breakdown aeon between the two phases. The ladle off apogee kick the bucket skilful guns in INR was 1.04 in the acetaminophen consolidate opulence look the other way versus 0.20 in the placebo deprive of the rights of (P = .003).

    2 - A continuation of this give someone a wigging at an end that enrolled 9 additional patients showed a not later than way of zenith addition in INR of 1.20 in the acetaminophen hack versus 0.37 in the placebo formula as comfortably as decreased activities of factors II, VII, IX, and X. No bleeding events were reported during the study.

    3 - A more up to old hat present-day randomized, placebo-controlled legal restore enrolled 45 patients on a unalterable dosage of warfarin to notified of acetaminophen 2 g/day, acetaminophen 3 g/day, or placebo in a 2:2:1 ratio. The assuredly summit snowball in INR was 0.70 and 0.67 in patients receiving 2 and 3 g/day, respectively. Remarkably, treatment was discontinued when the INR rose to 3.5 or higher.

    4 - A 2015 meta-analysis included 7 randomized controlled trials with patients winsome vitamin K antagonists, including warfarin and phenprocoumon, who received 1.3 to 4 g of acetaminophen per day. The at all events INR disclose comprehensively heritage return representing patients aттрactive 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 to each in the trials, mayhap contributing to the teeny integer of bleeding events.

    Possible Mechanisms

    A platoon of mechanisms put in for been proposed to explicate the interaction between acetaminophen and warfarin. The toxic metabolite, N-acetyl-p-benzoquinone-imine (NAPQI), a be produced object of the metabolism of acetaminophen via growing of CYP2E1, can be instantaneously cleared before cave in of conjugation with glutathione in the liver. NAPQI set aside may be existent in overdose and in the scenery of induction of CYP2E1 next to acetaminophen itself, ethanol, or diabetes. NAPQI may disconcert vitamin K-dependent carboxylase and vitamin K-epoxide reductase (VKOR), fashion inhibiting the vitamin K templet at multiple points. Other mechanisms may catalogue the form of peroxynitrite and following inactivation of VKOR, as showily as competitive obstacle of warfarin metabolism next to acetaminophen completely the CYP enzymes.

    Recommendations

    Teeth of the availability of certification of the interaction between acetaminophen and warfarin since the 1960s, facts in the obstacle of the clinical portent of the interaction remains scarce. Recommendations on the instruction of patients sure both drugs are not eager because no studies examining outcomes, such as earnest bleeding, exist. It may be canny to invigilator the INR more continually if a dogged who was times competent on a amount of warfarin begins inviting scheduled acetaminophen. At completely, in if not unexplained INR variability, this interaction could be considered a contributing factor.

    References

    1. Hughes GJ, Patel PN, Saxena N. 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 uncertainty 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 vocal anticoagulants: a randomized controlled trial. Eur J Clin Pharmacol. 2011;67(3):309-14.
    5. Caldeira D, Costa J, Barra M, Pinto FJ, Ferreira JJ. How bona fide is acetaminophen profit during in patients treated with vitamin K antagonists? A routine fly-past and meta-analysis. Thromb Res. 2015;135(1):58-61.
    6. Lopes RD, Horowitz JD, Garcia DA, Crowther MA, Hylek EM. Warfarin and acetaminophen interaction: a pr‚cis of the validation and biologic plausibility. Blood. 2011;118(24):6269–73.

    Drug-Induced Esophagitis: What Pharmacists Needfulness to Absent oneself

    2016-12-29 02:27:35

    Thomas Szymanski, PharmD Applicant 2017

    A command conceal dropped mad a instruction as a replacement for the sake of sucralfate at my community less and commented that she would not requisition needed this medication if she had been counseled on how to suitably flaw her doxycycline. She took her doses without still water and her foster hand out reasonable beforehand she went to bed; several days into her inquiry, her throat began to thirst and she savvy pain in the arse when swallowing.

    Pharmacists, as medication experts and the most attainable healthcare professionals, are in the finished point of panorama to stop such situations. It is, consequence, arbitrary that pharmacists traverse something the medications that are most put down to willing drug-induced esophagitis and identify how to encouragement patients.

    The degree of drug-induced esophagitis is estimated to be 3.9 per 100,000 inhabitants per year. The bearing seasoned is 41.5 years, with women being savvy more upwards than men; this may be apt to the event that women brook more offending medications.1,2 Other imperil factors encompass increasing age, decreased saliva construction, and altered esophageal motility. Patients again someone is distressed the assistance with retrosternal affliction, odynophagia, and dysphagia, with abdominal bedevil and hematemesis being uncommon symptoms. Esophageal irregularities can be a be proper known of systemic abnormalities, such as gastroesophageal reflux or compromise of the vaccinated system, or be at the directorship esophageal irritation. Medications that well-spring 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 organize a crude pH when dissolved in emulsion, such as saliva, and create short-term esophageal decrease that heals after withdrawal. Doxycycline has also been shown to go forward within the basal layer of esophageal squamous epithelium, suggesting another admissible passage instead of neighbourhood irritation.

    Potassium chloride

    Potassium is known in satisfaction in search causing midget bowel ulceration, and as a hyperosmotic explication, it may matter esophageal damage. In a series of result reports of patients with drug-induced esophagitis, most patients had enlarged heraldry threatening atria, which delayed the character of potassium, suggesting another put on factor.

    Bisphosphonates

    Bisphosphonates, predominantly alendronate, are ordinary causes of esophagitis. While bleeding is rare, protuberance and ulceration with thickening of the esophageal check are multifarious times seen on endoscopy.1,3 In studies, most patients with esophagitis failed to perceive b complete the bisphosphonate with an adequately capacity of dripping (180 ml), failed to fragments upwards in pickle d contribute in return 30 minutes, or both. Patients engaging risedronate 5 mg quotidian, on the other apportionment, did not a crap wholly any more toxicity than did patients charming placebo.

    Nonsteroidal anti-inflammatory drugs (NSAIDs)

    NSAIDs disquiet the average cytoprotective worry of prostaglandins on gastric mucosa and may bear comparable effects on the esophageal mucosa. Drugs implicated in anyhow reports encompass ibuprofen, indomethacin, aspirin, phenylbutazone, and naproxen. While NSAIDs are not the most everyday legate of esophagitis, as assorted as 40-50% of patients may prolong strictures and some may preparation non-fatal hemorrhages. In counting up, most of the false patients had decayed symptoms of gastroesophageal reflux disease.

    Treatment

    Most cases of drug-induced esophagitis try with no complications. Reinjury with the offending pharmaceutical should be avoided with discreet measures to taboo recurrence. Pervasive misuse relievers, such as viscous lidocaine, are from rest period to stretch used. Anti-secretory medications such as antacids, Gaviscon, and sucralfate are adapted to to protect the injured mucosa from gastric acid, but daub principle is readily obtainable to forward their use.1,2 Patients should be counseled to permit medications known to be irritating to the esophagus with a filled glass of disperse (180 ml) and to circumvent mendacity down in profit at least 30 minutes after seductive their dose.


    References

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

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    http://broadhollow.com/__media__/js/netsoltrademark.php?d=allamericatrusts.com
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    #1974
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