Isoniazid Acetaminophen

E1 Chlorzoxazone, isoniazid, acetaminophen, halothane, enflurane, methoxyflurane Dimethylnitrosamine, benzene, halogenated alkanes (eg, CCLj) acylonitrile, alcohols, aniline, styrene, vinyl chloride Chlorzoxazone (6-OH), [p-nitrophenol]... 

E1 Ethanol, isoniazid Acetaminophen, ethanol (minor), halothane... 

A Ferric chloride test (positive greenish-gray color) None Fresh or frozen random (U) Keep frozen (-20 C) until analyzed Screening testing only. May not be positive in all patients or between acute episodes. May be positive in other conditions with oxoacids. False positives with phenylthiazines, isoniazid, acetaminophen and other medications... 

Acetaminophen may alter blood glucose test results, causing falsely lower blood glucose values. Use with the barbiturates, hydantoins, isoniazid, and rifampin may increase the toxic effects and possibly decrease the therapeutic effects of acetaminophen. The effects of the loop diuretics may be decreased when administered with acetaminophen. Hepatotoxicity has occurred in chronic alcoholics who are taking moderate doses of acetaminophen. 

The effects of warfarin may increase when administered with acetaminophen, NSAIDs, beta blockers, disulfiram, isoniazid, chloral hydrate, loop diuretics, aminoglycosides, cimetidine, tetracyclines, and cephalosporins. Oral contraceptives, ascorbic acid, barbiturates, diuretics, and vitamin K decrease the effects of warfarin. Because die effects of warfarin are influenced by many drugp, die patient must notify die nurse or die primary healdi care provider when taking a new drug or discontinuing... 

Acetaminophen, bosentan, diclofenac, isoniazid, lovastatin, methyldopa, niacin, nefazodone, phenytoin, propylthiouracil, rifampin, trazodone, valproic acid, and venlafaxine... 

Drugs that may interact with isoniazid include acetaminophen, carbamazepine, chlorzoxazone, disulfiram, enflurane, hydantoins, ketoconazole, rifampin, and theophylline. 

Other drugs are metabolised by Phase II synthetic reactions, catalysed typically by non-microsomal enzymes. Processes include acetylation, sulphation, glycine conjugation and methylation. Phase II reactions may be affected less frequently by ageing. Thus according to some studies, the elimination of isoniazid, rifampicin (rifampin), paracetamol (acetaminophen), valproic acid, salicylate, indomethacin, lorazepam, oxazepam, and temazepam is not altered with age. However, other studies have demonstrated a reduction in metabolism of lorazepam, paracetamol (acetaminophen), ketoprofen, naproxen, morphine, free valproic acid, and salicylate, indicating that the effect of age on conjugation reactions is variable. 

A minor asymptomatic increase in liver aminotransferase is seen in 10 to 20% of patients, whereas fatal hepatitis is seen in fewer than 1% of isoniazid recipients. Risk factors for hepatitis include underlying liver disease, advanced age, pregnancy, and combination therapy with acetaminophen. Early recognition and prompt discontinuation of the drug is recommended to prevent further damage to the liver. 

E1 Acetaminophen, chlorzoxazone, enflurane, halothane, ethanol (a minor pathway) Ethanol, isoniazid 4-Methylpyrazole, disulfiram... 

Liver drug toxicity may be increased by enzyme inducers and a number of examples are known. Thus, carbon tetrachloride (16), trichlor-ethylene (17), toluene (18), hycanthone (19), acetaminophen and isoniazid (20), and metotrexate (21), among other drugs and chemicals, have been studied in this respect. 

Human CYP2E1 is one of the most efficient P450s to catalyze the oxidation of acetaminophen to NAPQI (157-159). Ethanol and isoniazid cause a time-dependent inhibition and induction of acetaminophen oxidation to NAPQI in humans (160,161) that can decrease risk for hepatotoxicity over the interval of concurrent administration and increase risk for hepatotoxicity a few hours after removal of ethanol or isoniazid. The latter induction phase of CYP2E1 may, in part, be responsible for cases of acetaminophen hepatotoxicity associated with the use of ethanol (162-165) or isoniazid (166-168). However, the induction is modest (2- to 3-fold) therefore, other susceptibility factors, genetic and others such as decreased glutathione stores and nutritional status, are likely to play an important role in some individuals (169-174). 

Zand R, Nelson SD, Slattery JT, et al. Inhibition and induction of cytochrome P450 2E1 catalyzed acetaminophen oxidation by isoniazid in humans. Clin Pharmacol Ther 1993 54 142-149. 

Murphy R, Scartz R, Watkins PB. Severe acetaminophen toxicity in a patient receiving isoniazid. Ann Intern Med 1990 113 799-800. 

Moulding TS, Redeker AG, Kanel GC. Acetaminophen, isoniazid, and hepatic toxicity. Ann Intern Med 1991 114 431. 

CYP2E1 Ethanol Acetaminophen Ethanol Isoniazid Disulfiram (Yes)" Chlorzoxazone... 

Numerous studies have demonstrated an apparent relationship between metabolite formation and toxicity. The N-hydroxylation of phenacetin may play a role in drug-induced hepatic necrosis . Similarly, N-hydroxylation may mediate acetaminophen hepatotoxicity . Acetylhydrazine and isopropylhydrazine, metabolites of isoniazid and iproniazid, may initiate hepatotoxicity through covalent binding of an electrophilic intermediate (see Chapter 32) . 

Hepafotoxicity from chronic paracetamol (acetaminophen) therapy in adults have been reported in the literature, but compared to the acute toxicity seen with deliberate or accidental overdoses, these are very few. The majorify of fhese are associafed wifh chronic efhanol intake, smoking, isoniazid, rifampin, phenobarbifal and phenyfoin (inducers of the cytochrome P450 system). Short-term fasting and... 

CYP2A6 <5 1-2 Acetaminophen Carbamazepi ne Cyclophosphamide Selegiline Flunitrazepam Nicotine Clotrimazole Isoniazid Methoxypsoralen Valproic acid Dexamethasone Phenobarbital Rifampin... 

Cronqvist, J. Nilsson-Ehle, I. Determination of acyclovir in human serum hy hi -performance liquid chromatography. J.Liq.Chromatogr., 1988, 11, 2593-2601 [serum non-interfering acetaminophen, allopurinol, baclofen, carbacholine, cefuroxime, chlorpropamide, cilastatin, cloxacillin, diazepam, di-cumarol, digoxin, flucloxacillm, furosemide, fusidic acid, fusidic, glipizide, heparin, hydrochlorothiazide, imipenem, insulin, isoniazid, ketoprofen, metronidazole, naproxen, perphenazine, phenytoin, prednisolone, propranolol, p3razinamide, p3ridoxine, ranitidine, rifampicin, rifampin, spironolactone, streptomycin, sulfamethoxazole, trimethoprim, warfarin]... 

Noninterfering acenocoumaron, acetaminophen, acetophenetidine, aspirin, benzodiazepines, bibenzepin, butriptyline, caffeine, chlorprothixene, clopenthixol, clothiapine, dix-yrazine, droperidol, fluphenazine, haloperidol, hydroxyzine, isoniazid, methotrimeprazine,... 

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