Inhibition aldehydes

N, O-Diacylated or O-alkylated N-hydroxysulfonamides release nitroxyl (HNO) upon hydrolysis or metabolic dealkylation, as determined by gas chromatographic identification of nitrous oxide in the reaction headspace [27-29, 38]. Scheme 7.5 depicts the decomposition of a representative compound (7) to a C-acyl nitroso species that hydrolyzes to yield HNO. Either hydrolysis or metabolism removes the O-acyl or O-alkyl group to give an N-hydroxy species that rapidly decomposes to give a sulfinic acid and an acyl nitroso species. This C-acyl nitroso species (8) hydrolyzes to the carboxylic acid and HNO (Scheme 7.5). These compounds demonstrate the ability to relax smooth muscle preparations in vitro and also inhibit aldehyde dehydrogenase, similar to other HNO donors [27, 29]. 

Most of the human experience with disulfiram has come from its use as an avoidance therapy for alcoholism. Metabolites of disulfiram inhibit aldehyde dehydrogenase, resulting in elevated levels of acetaldehyde after ethanol ingestion. Side effects include flushing of the face, tachycardia, severe headache, apprehension, hyperpnea, hypotension, dizziness, nausea, vomiting, and fainting. Severe reactions may include convulsions, myocardial infarction, and marked respiratory depression. ... 

Disulfiram metabolites include diethyl-dithiocarbamate and its metabolites, the moieties that irreversibly inhibit aldehyde... 

Cimetidine Cimetidine inhibits aldehyde oxidase and CYP3A4, the primary and secondary enzymes, respectively, responsible for zaleplon metabolism. Use an initial... 

It exerts its action by inhibiting aldehyde dehydrogenase enz5une. Disulfiram thus increases the concentration of acetaldehyde in body when ethanol is ingested by an individual pretreated with disulfiram. The symptoms and signs produced... 

Disulfiram Inhibits aldehyde dehydrogenase, causes aldehyde accumulation during ethanol ingestion Deterrent to relapse in individuals with alcoholism Toxicity Little effect on its own but severe and potentially dangerous flushing, headache, nausea, vomiting, and hypotension when combined with ethanol... 

Inhibits hepatic microsomal drug-metabolizing enzymes. Inhibits aldehyde dehydrogenase. 

A similar effect is exerted by the drug disulfiram (Antabuse), which has been used to discourage drinking and whose metabolites are thought to inhibit aldehyde dehydrogenase.95... 

Disulfiram (Antabuse) inhibits aldehyde dehydrogenase irreversibly, causing an increase in the level of acetaldehyde, formed from ethanol by the enzyme alcohol dehydrogenase. This results in nausea, vomiting, and other symptoms in the human—hence its use as a deterrent in alcoholism. Inhibition by disulfiram appears to be irreversible, the level returning to normal only as a result of protein synthesis. 

Oxidation of acetaldehyde is inhibited by disulfiram, a drug that has been used to deter drinking by alcohol-dependent patients undergoing treatment. When ethanol is consumed in the presence of disulfiram, acetaldehyde accumulates and causes an unpleasant reaction of facial flushing, nausea, vomiting, dizziness, and headache. Several other drugs (eg, metronidazole, cefotetan, trimethoprim) inhibit aldehyde dehydrogenase and can cause a disulfiram-like reaction if combined with ethanol. 

METRONIDAZOLE ALCOHOL Disulfiram-like reaction Metronidazole inhibits aldehyde dehydrogenase Avoid co-ingestion... 

ALCOHOL METRONIDAZOLE Disulfiram-like reaction. Unsteadiness, and incoordination caused by metronidazole may be aggravated by alcohol Metronidazole inhibits aldehyde dehydrogenase. Additive side-effects Avoid co-ingestion... 

Cephalosporins that contain a methyltetrazole-thiol side chain (as in cefamandole, cefmenoxime, cefmeta-zole, cefonizid, cefoperazone, ceforanide, cefotetan, cefotiam, latamoxef, and moxalactam) and chemically similar structures (cefepime, ceftriaxone) co-adminis-tered with alcohol can produce a disulfiram-like syndrome by inhibiting aldehyde dehydrogenase (195,202,203). 

Onh a small fraction of an urally administered dose of liini/oliibme Is absorbed. Approximately 5% uf the oral dose iteuble in the urine in the form of. several metabolites. S nu g.astniimestlnal distress has been reported with its use. Alr. li l should be avoided when fura/ulidone is being used Uv.iiisc ilw drug can inhibit aldehyde dehydrogenase. 

Certain drugs inhibit non-microsomal metabolic pathways. Metronidazole, like disulfiram, inhibits aldehyde dehydrogenase, the enzyme that normally oxidizes acetaldehyde to acetic acid in the metabolic pathway for ethanol. Allopurinol inhibits xanthine oxidase, the enzyme that catalyses the oxidation of hypoxanthine to xanthine and xanthine to uric acid. Because azathioprine and 6-mercaptopurine are metabolized by xanthine oxidase, the dosage of these drugs (synthetic xanthine analogues), when used concomitantly with... 

Inhibits aldehyde dehydrogenase, amylase, induction of collagcnase (which is modulated by cAMP), DNA repaiT and replication, DNA synthesis. 

Inhibits aldehyde oxidase, cholesterol acyltransferase, retinol fatty-acyltransferase. 

In the first, phenobarbital, by inhibiting aldehyde reductase, is thought to interfere with the metabolism of aldehyde generated by biogenic amines such as dopamine, norepinephrine, and serotonin. The accumulation of these aldehydes in the CNS has depressing properties, and this reduces the neuronal sensitivity to excitation. 

Antabuse inhibits aldehyde dehydrogenase, the enzyme responsible for oxidizing acetaldehyde to acetic acid, resulting in a buildup of acetaldehyde. Acetaldehyde causes the unpleasant physiological effects of intoxication intense flushing, nausea, dizziness, sweating, throbbing headaches, decreased blood pres-... 

Disulfiram inhibits aldehyde dehydrogenase. Thus, consumption of ethanol will produce increased levels of acetaldehyde which will form the toxic intermediates methanol and formaldehyde... 

Metronidazole inhibits aldehyde dehydrogenase and may cause a disulfiram-like reaction in patients who consume alcoholic beverages while taking the drug. The answer is (G). 

Cefoperazone Cefamandole Cefotetan Moxalactam Cefmetazole 102-156 min 30-50 min 3-4.6 h 114-150 min 72 min 3-4 mg/L One case of symptomatic hepatitis. All of these antibiotics have the /V-methyltetrazoletniol side chain which may inhibit aldehyde dehydrogenase to cause a disulfiramlike interaction with ethanol (see p 186) and coagulopathy (inhibition of vitamin K production). 

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