Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Both cimetidine therapy and cirrhosis individually interfere with normal elimination of various drugs. Cimetidine is often prescribed in patients with cirrhosis but there is incomplete data on its effect on drug elimination in cirrhotics. The purpose of this study was to address this issue. Eight stable cirrhotics were studied prior to and following 7 days of cimetidine administration, (300 mg orally q.i.d.). Chlordiazepoxide (Librium), which is eliminated by the liver after demethylation, and indocyanine green, which is removed by the liver without biotransformation, were used as probes. Consistent with the concept that cimetidine interferes with drug metabolism by inhibiting microsomal oxidation, chlordiazepoxide clearance in the cirrhotics was inhibited by cimetidine (p less than 0.05), but indocyanine green clearance was unaffected. As shown by us previously (Roberts, R. K. et al., Gastroenterology 1978; 75:479-485), untreated cirrhotics had substantially lower chlordiazepoxide clearance than did controls. The inhibitory effect of cimetidine on chlordiazepoxide clearance was less in cirrhotics than in controls (p less than 0.05). In all subjects, there was excellent correlation between initial clearance and magnitude of depression in clearance after cimetidine, i.e., the larger the initial clearance, the larger the change (r = 0.97, p less than 0.0001). Forty-eight hours after stopping cimetidine, chlordiazepoxide clearance returned to baseline in cirrhotics and controls. Our data demonstrate that cimetidine and cirrhosis may act additively to impair drug metabolism. This effect of cimetidine on chlordiazepoxide clearance is smaller in cirrhotics than in controls, but, because of impaired initial drug elimination in cirrhosis, it may result in adverse clinical effects.
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PMID:The effect of cimetidine on hepatic drug elimination in cirrhosis. 397 62

The potential respiratory interaction between morphine and cimetidine was studied by determining resting ventilation, PETCO2 and ventilatory response to added carbon dioxide in eight healthy volunteers on three separate occasions following administration of : (1) cimetidine 600 mg p.o., (2) morphine 10 mg IM, (3) morphine 10 mg IM preceded by cimetidine 600 mg p.o. Individual entry into the study was randomized and separated by at least one week. All measurements were determined at time 0, 30, 60, 120, 180, 240, 360, 480, 600, 720 minutes and at the end of 24 hours. In addition, serum morphine levels were measured in six subjects during the first six hours following morphine administration. Cimetidine alone had negligible respiratory effects. Morphine alone reduced resting ventilation, elevated PETCO2 and reduced the ventilatory response to added CO2, while the morphine-cimetidine combination caused a more profound depression of the CO2 response and delay in its recovery. No significant difference between resting ventilation and PETCO2 was observed. We conclude that cimetidine premedication interacts with morphine to prolong the respiratory depression but the magnitude of this interaction is small and clinically insignificant in healthy subjects. Caution, however, should be exercised in susceptible patients.
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PMID:Effect of cimetidine premedication on morphine-induced ventilatory depression. 642 25

The effect of cimetidine on the metabolism of methadone was investigated in hepatic microsomes isolated from male Sprague-Dawley rats. N-demethylation of methadone was determined by formation of formaldehyde. Cimetidine inhibited methadone N-demethylation in a noncompetitive manner with an IC50 of 5.3 X 10(-4) M. This observation is consistent with previous reports of microsomal enzyme inhibition by cimetidine and suggests that caution must be exercised when methadone and cimetidine are co-administered to patients in order to avoid excessive sedation or respiratory depression.
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PMID:Cimetidine inhibits the in vitro N-demethylation of methadone. 651 23

Cimetidine impairs the systemic clearance of a number of low extraction drugs and this study examines its effect on the oral clearance of the high extraction drug, chlormethiazole. Cimetidine (1 g/day for 7 days) caused the clearance of chlormethiazole to fall to 69% of pretreatment values. It also prolonged the elimination half-life by 60%. The findings indicate that the metabolism of chlormethiazole is inhibited by cimetidine and the co-administration of these drugs may lead to excess sedation and respiratory depression.
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PMID:Cimetidine impairs the elimination of chlormethiazole. 733 51

There has been a resurgence of interest in the use of monoamine oxidase (MAO) enzyme inhibitors for the treatment of depression. Unlike the first-generation MAO inhibitors, the current drugs are readily reversible in their action, resulting in far less concern about interactions with certain foods and drugs which could lead to serious pressor effects. Furthermore, the current drugs are far more selective in their actions as a result of the ability to affect either the MAO-A or the MAO-B isoenzyme. Moclobemide is an example of a reversible MAO-A inhibitor which has been extensively studied and whose pharmacokinetic, clinical pharmacological and toxicological profiles have been thoroughly defined. Moclobemide has a short disposition half-life and intermediate values for systemic clearance and volume of distribution; half-life increases somewhat with dose. The drug is completely metabolised by the liver. Moclobemide is rapidly and completely absorbed following oral administration in a variety of dosages and forms. The drug has a high intrinsic (apparent oral) clearance which results in a substantial hepatic first-pass effect and, while there is marked interindividual variation, differences within an individual are small. A time- and dose-dependence is observed with multiple oral administration: clearance decreases with administration during the first week and thereafter remains constant. The exact mechanism of this effect is not known, but it may reflect inhibition of elimination by metabolites (the kinetics may always be described as being first-order). Moclobemide disposition is not affected by renal disease, nor is there substantial alteration with advanced age. Liver disease causes a dramatic reduction in clearance; dosage must be adjusted for patients with liver disease. There is minimal transfer of the drug into breast milk, such that breast-feeding neonates are exposed to only a very small dose of the drug. Moclobemide administration results in a minimal interaction with exogenous amines (e.g. tyramine and pressor amine drugs); the so-called 'cheese effect' is therefore of little concern. As a result, the drug has an excellent tolerability profile both within the therapeutic dose range and in overdose (no deaths have been attributed to moclobemide intoxication per se). Cimetidine inhibits the elimination of moclobemide. Moclobemide appears to affect several isoenzymes of the cytochrome P450 (CYP) system (CYP2C19, CYP2D6 and CYP1A2). The adverse events profile of moclobemide indicates only mild and transient effects at a relatively low rate of occurrence.
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PMID:Clinical pharmacokinetics of the monoamine oxidase-A inhibitor moclobemide. 858 17

The number of persons with drug induced sexual dysfunction has risen simultaneously with the unending increase in the number of commercially available drugs. Sexual dysfunction may seriously impair the human psyche. Patients do not often admit to sexual dysfunction, however, so physicians often miss the symptoms entirely. In addition, they may attribute them to other causes, such as depression. Drugs disrupt all 3 neurophysiologic phases of sexual response (desire, excitement, and orgasm), especially in men, either causing a decrease or loss of libido, impotence (the most common symptom), or failure of ejaculation or anorgasmia. The mechanisms involved are not well understood. Researchers do know, however, that the drug cimetidine (Tagamet) blocks androgen receptors, decreases testosterone synthesis, and induces higher circulating levels of estradiol resulting in impotence and breast enlargement in men. Antihypertensive drugs have a higher frequency of causing sexual dysfunction, particularly impotence, than other drugs. Some also induce or worsen depression that can in turn cause or intensify sexual dysfunction. Both legal and illegal psychoactive drugs act on multiple sites thus often stimulating sexual dysfunction. Further, some hormonal drugs also induce sexual side effects, such as norethindrone and progesterone. Physicians who prescribe a drug associated with sexual side effects should inform patients about their possible occurrence and recommend that they be aware of the symptoms. They should ask these patients do not usually offer this information themselves. If sexual dysfunction develops, physicians can reduce the dosage or switch to an alternative drug. At that time, they should express optimism that the sexual dysfunction will cease.
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PMID:Sexual side effects of drugs. 1231 40


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