Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0016382 (flushing)
 6,387 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hypertensive patients, particularly the elderly, may often suffer from other diseases. Therefore, antihypertensive compounds should not negatively affect such disorders. Felodipine is a calcium antagonist that has potentially beneficial effects in angina pectoris and congestive heart failure. Further, it does not adversely affect lung function in asthmatic patients or glucose tolerance in patients with diabetes. Preliminary investigations also indicate that felodipine has no negative influence on plasma lipid levels. Although felodipine seems to be safe in most patients, treatment with felodipine should at present be avoided in pregnant women, since digital anomalies have been observed in rabbit fetuses. The adverse effects seen during treatment with felodipine are usually mild and transient and generally related to the vasodilatory action of the drug, the most common being ankle edema, headache, flushing, dizziness, and palpitations. The only significant drug interactions with felodipine occur with inducers and inhibitors of the cytochrome P-450 system, which is responsible for the metabolism of felodipine.
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PMID:The safety of felodipine. 169 36

The metabolism of benzanthrone, a commonly used dy intermediate, by rat hepatic microsomes was investigated using thin layer chromatography (TLC) analysis. Incubation of benzanthrone with hepatic microsomes in the presence of NADPH generating system produced at least seven fluorescent metabolites on TLC plates. TLC spots numbered II, III, IV, V and VI were the major metabolites obtained from hepatic microsomes with the Rf values of 0.53, 0.45, 0.38, 0.33 and 0.26, respectively. Metabolites VII and VIII were faint bands with Rf values of 0.08 and 0.04, respectively. Preincubation of hepatic microsomes with either 1-benzyl-imidazole (10(-4)M) or SKF-525 A (10(-4)M) or metyrapone (10(-3)M) or flushing with carbon monoxide substantially inhibited the benzanthrone metabolism. alpha-Naphtho-flavone (10(-4)M) did not cause any change in hepatic microsomal metabolism of benzanthrone. Oral administration of benzanthrone to animals yielded at least six urinary metabolites. TLC spots numbered II, III, IV, V and VI in the urine were same as those of hepatic microsomal metabolites. However, one of the urinary metabolite numbered IX which stays at the origin of TLC plate with the Rf value of 0.05 may be a conjugate. Our results suggest that benzanthrone acts as a substrate for hepatic heme protein, cytochrome P-450 and that some of the metabolites are excreted in urine.
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PMID:Benzanthrone: a new substrate for hepatic microsomal cytochrome P-450. 275 86

Biotransformations of drugs are controlled or strongly affected by genetic factors. During the past few years several genetic deficiencies of drug-metabolizing reactions catalyzed by members of the family of cytochrome P-450 were observed. Choice of the appropriate drug to study and attention to urinary metabolites have been the essential ingredients for the recent discovery of genetic deficiencies of drug metabolism in man which include recessive deficiency of debrisoquine/sparteine metabolism and of mephenytoin metabolism. The clinical significance of these defects is discussed. Ethanol after metabolism to acetaldehyde is further metabolized to acetic acid by aldehyde dehydrogenase. Numerous isozymes of aldehyde dehydrogenase exist, one of which possesses a high affinity for acetaldehyde. Approximately 40% of the Oriental population lack this high affinity isozyme so that in these individuals who may have symptoms of flushing and other unpleasant effects the acetaldehyde formed is destroyed only at high plasma concentrations.
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PMID:Genetics of drug transformation. 351 92

The present work examines the mechanism of testicular toxicity of acrylonitrile. In testicular centrifugal fractions from Sprague Dawley rats, the metabolism of VCN to cyanide (CN-) was highest in the microsomal fraction and required NADPH for maximum activity. This biotransformation of VCN to CN- was characterized with respect to time (30 min), microsomal protein concentration (1.5 mg ml(-1)), pH (7.5) and temperature (37 degrees C). The V(max) of the reaction was 65.1 pmol CN- mg protein(-1) min(-1) and K(m) was 88.6 micromol VCN. Flushing the microsomes with carbon monoxide (CO)(4:1, CO/O2 v/v), addition of benzimidazole (1 mM) or addition of SKF 525-A (5x10(-4) M) to incubation mixtures significantly inhibited VCN metabolism by 49%, 54% and 37.4% respectively. Activation of VCN to CN- was markedly increased in microsomes obtained from phenobarbital (PB)-treated rats (128.2%). Addition of glutathione (GSH), L-cysteine, D-penicillamine or 2-mercaptoethanol significantly enhanced the release of CN- from VCN 126%, 247%, 202% and 129% of the control value respectively. These findings indicate that VCN is metabolized in the testis via cytochrome P-450 dependent mixed function oxidase system.
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PMID:In-vitro testicular bioactivation of acrylonitrile. 917 82

Sildenafil is the first orally administered available treatment for erectile dysfunction. It produces a selective vasodilatation of corpus carvernosum, mediated by the inhibition of phosphodiesterase 5, an enzyme that degrades GMPc. Its therapeutic efficacy has been demonstrated in organic as well as psychogenic or mixed erectile dysfunction. Most of its adverse effects, such as headache, flushing, gastroesophageal reflux and color vision disturbances, are related to the mechanism of action. Its interactions with other medications, can have severe adverse consequences. The concomitant use of sildenafil with drugs that release nitric oxide in their molecule, can produce severe hypotension. In patients with coronary heart disease or cardiac failure, this interaction can cause death. Sildenafil is metabolized in the liver through cytochrome P-450. This enzymatic system can be inhibited by cimetidine, ketoconazole or erythromycin. These drugs can increase plasma concentrations of sildenafil. We must identify the groups of patients that will have a better response to the drug and those in whom the drug will be useless. We must also know more about the security profile of the drug. With time, we will know the real role of sildenafil in the treatment of erectile dysfunction.
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PMID:[Sildenafil (viagra) at the time of warnings]. 1034 69