Isoniazid Ethanol

Dipping solution Dissolve 1 g isonicotinic acid hydrazide (4-pyridinecarboxylic acid hydrazide, isoniazide) in 100 ml ethanol and add 500 gl trifluoroacetic acid [1] or 1 ml glacial acetic acid. 

Low antiepileptic drug levels, drug overdose (e.g., cocaine, isoniazid, theophylline, phenothiazine), ethanol-related, and drug withdrawal... 

Irradiation of an alcoholic solution of the antitubercular drug isoniazid (261) with a low-pressure mercury lamp by Ninomiya and Yamamoto gave isolated yields of the hydrazone (262, 60%) and the hydrazide (264, 17%). Nicotinic and picolinic acid hydrazides reacted similarly, as did other alcohols. The production of (262) was easily understood since it was known that photolysis of ethanol gave acetaldehyde which would react spontaneously with the... 

Chiang and Lin also irradiated alcoholic solutions of isoniazid, but used a high-pressure mercury lamp. From the methanol solution they isolated small yields of isonicotinic acid, isonicotinamide, the hydrazone (263) and the bishydrazide (265). From the ethanolic solution, they obtained isonicotinamide, the hydrazone (262) and the bishydrazide (265). As before, (262) was assumed to arise via photo-oxidation of the solvent. The other products were explained as resulting from either CO-N or N-N bond homolysis [163]. 

Amiodarone Benzodiazepines Chloramphenicol Cimetidine Disulfiram Ethanol (acute ingestion) Fluconazole Isoniazid Metronidazole Miconazole Omeprazole Phenacemide Phenylbutazone Succinimides Sulfonamides Trimethoprim Valproic acid Salicylates Tricyclic antidepressants Valproic acid... 

Ethanol Halodiane Isoniazid Nitrofurantoin Phenylbutazone Urediane 6-Mercaptopurine Vinylidene chloride... 

Following the development of the test, an in-house validation was conducted to evaluate the performance of FETAX compared to the results in the rat and/or rabbit. Thirteen reference chemicals were tested including eight compounds known to be teratogenic in rats and/or rabbits (caffeine, retinoic acid, hydroxyurea, ethanol, cyclophosphamide, nicotine, acetylsalicylic acid, dexametha-sone) and five non-teratogens (isoniazid, saccharin, paracetamol, penicillin G, sildenafil). The estimation of teratogenicity in rats and rabbits was based on published data (9). 

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

Park KS, Sohn DH, Veech RL, et al. Translational activation of ethanol-inducible cytochrome P450 (CYP2E1) by isoniazid. Eur J Pharmacol 1993 248 7-14. 

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). 

Induction by increased enzyme synthesis has been described for induction of CYP2B1/2 by octamethylcyclotetrasiloxane (Sarangapani et al. 2002) and CYP1A1 and CYP1A2 by TCDD via interaction with the Ah-receptor (Andersen 1995 Andersen et al. 1997). Induction by decreased enzyme degradation has been described by Chien et al. (1997) for induction of CYP2E1 by ethanol, acetone, and isoniazid via enzyme stabilization. Exposure to such enzyme inducers and stabilizators would result in increasing the clearance of all other coexposed chemicals that are metabolized by the stabilized enzyme. 

Ethanol, isoniazid Diallyl sulfide Dimethylnitrosamine N-demethylase and p-nitrophenol oxidase... 

Lactic acidosis is also caused by (1) drugs and toxins, such as ethanol, methanol, biguanides, isoniazid (see previous discussion), and streptozotocin (2) acquired and hereditary defects in enzymes involved in gluconeogenesis (3) disorders such as severe acidosis, uremia, liver failure, tumors, and seizures (4) anesthesia and (5) abnormal intestinal bacteria producing n-lactate (described in Chapter 25). 

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

Pancreatic dysfunction, heralded by large increases in serum amylase and lipase, is associated with the use of several reverse-transcriptase inhibitors (RTIs). Didanosine appears to be the worst offender, and pancreatitis is the most characteristic adverse effect of this particular NRTI. Conditions enhancing susceptibility to drug-induced pancreatic dysfunction include hypertriglyceridemia, hypercalcemia, and history of excessive ethanol use. Liver dysfunction including hepatitis may occur with the antitu-bercular drugs, isoniazid, and pyrazinamide. Cholestasis is associated with the estolate form of erythromycin. 

Barbiturates Omeprazole Rrfampicin Tobacco smoke Ethanol Dexamethasone Isoniazid... 

E1 Chlorzoxazone 6-hydroxylation" p-Nitrophenol hydroxylation"" iV-N itrosodimethylamine A -demethylationP Ethanol Isoniazid 4-Methylpyrazole "" Diethyldithiocarbamate"" Chlorzoxazone... 

Because benzodiazepines do not significantly induce the synthesis of hepatic CYPs, chronic benzodiazepine administration usually does not result in the accelerated metabolism of benzodiazepines or other substances. Cimetidine and oral contraceptives inhibit N-dealkylation and 3-hydroxylation of benzodiazepines, as do ethanol, isoniazid, and phenytoin to a lesser degree. These reactions usually are reduced to a greater extent in elderly patients and in patients with chronic liver disease than are those involving conjugation. 

Drug Interactions Barbiturates combine with other CNS depressants to cause severe depression ethanol is the most frequent offender, and interactions with first-generation antihistamines also are common. Isoniazid, methylphenidate, and monoamine oxidase inhibitors also increase the CNS-depressant effects. Other prominent drag interactions occin as a result of the induction of hepatic drug-metabolizing enzymes by barbiturates see above). 

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