Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023890 (cirrhosis)
 42,195 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Chlordiazepoxide was the first benzodiazepine derivative made available for clinical use. The metabolic pathway of chlordiazepoxide is complex, since the drug is biotransformed into a succession of pharmacologically active products: desmethylchlordiazepoxide, demoxepam, desmethyldiazepam, and oxazepam. The elimination half-life (tl/2beta) of chlordiazepoxide following single doses, in healthy individuals generally ranges from 5 to 30 hours, and the volume of distribution from 0.25 to 0.50 liters/kg. The hepatic extraction ratio is well under 5%. Elimination of the parent compound is mirrored by formation of the first active metabolite. Clearance of chlordiazepoxide is reduced and tl/2beta is prolonged in the elderly, in those with cirrhosis, and in those receiving concurrent disulfiram therapy. Oral chlordiazepoxide is rapidly and completely absorbed, but intramuscular injection is painful and results in slow and erratic absorption. Multiple-dose therapy with chlordiazepoxide results in accumulation of the parent compound, as well as two or more of its active metabolites. The rate and extent of accumulation varies considerably between individuals. A relation between plasma concentrations of chlordiazepoxide and its metabolites to clinical effects has been suggested in some studies and is currently under further investigation.
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PMID:Clinical pharmacokinetics of chlordiazepoxide. 35 14

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

This trends ecological study analyzes, across 17 autonomous communities of Spain from 1989 to 1998, the relationship between mortality (total and by main causes of death) and power relations (type of government: social democratic (SDP), conservative (CDP), and others), labor market variables, welfare state variables, income inequality, absolute income, poverty, and number of civil associations. The authors conducted a descriptive analysis; a bivariate analysis (Pearson correlation coefficients) between mortality and each of the independent variables; and a multivariate analysis, adjusting multilevel linear regression models. All dimensions of the conceptual power relations model were related to premature mortality in the direction hypothesized. The cross-pooled multilevel regression models show that total premature mortality in males, male and female cerebrovascular mortality, male and female cirrhosis mortality, and male lung cancer mortality decreased somewhat more in communities where primary health care reform was implemented more quickly. Premature mortality decreased somewhat more in SDP than in CDP communities for male and female total premature mortality, cerebrovascular mortality, and cirrhosis mortality, and male lung cancer mortality. These results are in accord with earlier studies that found a relationship among health indicators and variables related to labor market, welfare state, income inequalities, civil associations, and power relations.
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PMID:Power relations and premature mortality in Spain's autonomous communities. 1475 56