Cimetidine metabolic pathways

Taken with alcohol they potentiate the sedative effects and impairment of psychomotor performance. Hepatic enzyme induction by barbiturates or nicotine may reduce plasma levels. Cimetidine may increase levels by enzyme inhi bition. Some antipsychotic drugs may compete for similar metabolic pathways. 

Antacids reduce the absorption and enzyme-inducing drugs may decrease serum levels. Cimetidine and propranolol both increase serum levels. There can be competition for metabolic pathways by some tricyclic antidepressants (TCAs) and SSRIs (especially fluoxetine) which may increase serum levels. 

Zaleplon is primarily metabolized by aldehyde oxidase and use with inhibitors of this enzyme, such as cimetidine, may result in increased plasma concentrations of zaleplon. Zaleplon is also partly metabolized by the cytochrome P450 isoenzyme CYP3A4 and, consequently, caution is advised when zaleplon is given with drugs that are substrates for, or potent inhibitors of, this isoenzyme. Cimetidine is also an inhibitor of CYP3A4 and thus inhibits both the primary and secondary metabolic pathways of zaleplon. Use with rifampicin or other potent enzyme-inducing drugs may accelerate the metabolism of zaleplon and reduce its plasma concentrations [40]. 

Cimetidine. Since cimetidine may inhibit certain metabolic pathways, an increased action of concurrently administered drugs that are metabolized via these pathways should be anticipated. For example, cimetidine may inhibit the metabolism of diazepam and certain other benzodiazepines, and the sedative effect of these agents may be enhanced as a result of the interaction. Particular caution is necessary in older patients who may exhibit an increased sensitivity to the depressant... 

Cimetidine inhibits the liver enzymes associated with oxidative metabolism. Hence, the serum levels of most benzodiazepines affected by this metabolic pathway (aiprazoiam, diazepam, cbiordiazepoxide, fiurazepam, nitrazepam, and triazoiam) were found to be increased when cimetidine was co-administered. Benzodiazepines metabolized by glucuronide conjugation (iorazepam, oxazepam, and temazepam) are not affected by cimetidine. Ranitidine probably has no significant interaction with most benzodiazepines. 

Lorazepam, oxazepam and temazepam are metabolised by a different metabolic pathway involving glucuronidation, which is not affected by cimetidine, and so they do not usually interact. 

Grygiel JJ, Miners JO, Drew R, Biricett DJ. Differential effects of cimetidine on theq>hylline metabolic pathways. EurJ Clin Pharmacol (1984) 26,335-40. 

Cimetidine reduces the hepatic metabolism of drugs metabolized via the cytochrome P450 pathway, delaying elimination and increasing serum levels. 

Omeprazole, like cimetidine, can impair benzodiazepine metabolism and lead to adverse effects (SEDA-18, 43). Other drugs, including antibiotics (erythromycin, chloramphenicol, isoniazid), antifungal drugs (ketoconazole, itraconazole, and analogues), some SSRIs (fluoxetine, paroxetine), other antidepressants (nefazodone), protease inhibitors (saquinavir), opioids (fentanyl), calcium channel blockers (diltiazem, verapamil), and disulfiram also compete for hepatic oxidative pathways that metabolize most benzodiazepines, as well as zolpidem, zopiclone, and buspirone (SEDA-22,39) (SEDA-22,41). 

METFORMIN H2 RECEPTOR BLOCKERS -CIMETIDINE, RANITIDINE t level of metformin and risk of lactic acidosis. The onset of lactic acidosis is often subtle with symptoms of malaise, myalgia, respiratory distress and t nonspecific abdominal distress. There may be hypothermia and resistant bradyarrhythmias Metformin is not metabolized in humans and is not protein-bound. Competition for renal tubular excretion is the basis for T activity or retention of metformin. Cimetidine competes for the excretory pathway A theoretical possibility. Need to consider l dose of metformin or avoidance of co-administration. Warn patients about hypoglycaemia - For signs and symptoms of hypoglycaemia, see Clinical Features of Some Adverse Drug Interactions, Hypoglycaemia... 

The metabolism of lorazepam (e.g., Ativan), oxazepam (e.g., Serax), and temazepam (e.g., Restoril) are not likely to be affected, and one of these agents may be preferred when a benzodiazepine is indicated in a patient being treated with cimetidine. The experience with ranitidine (e.g., Zantac), famotidine (Pepcid), and nizatidine (Axid) suggests that these agents are not likely to inhibit hepatic enzyme systems, and these other histamine H2-receptor antagonists are less likely than cimetidine to interact with other drugs that are metabolized via these pathways. 

Drug interactions Drugs utilizing the CYP2D6 (i.e., f luoxetine, cimetidine) or the CYP3A4 (i.e, macrolides, antiretrovirals) pathways may inhibit opioid metabolism and potentiate side effects. Drugs such as benzodiazepines and barbiturates should be used cautiously in combination with opioids, as they may potentiate respiratory depression or sedative effects. 

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