Acetylator phenotype and the antihypertensive response to hydralazine. 1975

A J Jounela, and M Pasanen, and M J Mattila

Twenty-three out-patients with mild or moderate essential hypertension have been treated with a combination of hydralazine (37.5-150 mg daily) and oxprenolol (60 mg daily). Before treatment the patients were phenotyped for polymorphic acetylation by means of the sulphamethazine test: 12 proved to be slow and 11 rapid acetylators. A significant correlation was found between daily doses of hydralazine and the plasma hydralazine levels, separately in slow (r=0.480) and in rapid (r=0.580) acetylators. The antihypertensive response to hydralazine correlated well to plasma hydralazine levels. The mean fall of BP in slow acetylators was 33/23 mmHg in supine and 20/18 mmHg in standing position. The corresponding values in rapid acetylators were 22/15 and 21/15 mmHg. The average daily doses of hydralazine needed for these responses were 1.3 mg/kg in slow and 1.6 mg/kg in rapid acetylators. To reduce the systolic BP by 20 mmHg, 1.0 mg/kg of hydralazine was needed in slow acetylators; rapid acetylators needed a significantly higher dose of 1.4 mg/kg. During a follow-upof 1 year there have been virtually no side-effects. The results tally with the previous finding of Zacest and Koch-Weser, who demonstrated a similar correlation during the triple-drug regimen. It seems as if hypertensive patients can be succesfully treated with hydralazine and beta-blocking drug without knowledge of the patient's acetylator phenotype. However, acetylator status is a determinant of tissue levels and long-term toxicity of hydralazine, and patients should be phenotyped because beta-blockers may mask the warning side-effects.

UI MeSH Term Description Entries
D006973 Hypertension Persistently high systemic arterial BLOOD PRESSURE. Based on multiple readings (BLOOD PRESSURE DETERMINATION), hypertension is currently defined as when SYSTOLIC PRESSURE is consistently greater than 140 mm Hg or when DIASTOLIC PRESSURE is consistently 90 mm Hg or more. Blood Pressure, High,Blood Pressures, High,High Blood Pressure,High Blood Pressures
D008297 Male Males
D008875 Middle Aged An adult aged 45 - 64 years. Middle Age
D010096 Oxprenolol A beta-adrenergic antagonist used in the treatment of hypertension, angina pectoris, arrhythmias, and anxiety. Coretal,Koretal,Oxprenolol Hydrochloride,Slow Trasicor,Tevacor,Trasicor,Hydrochloride, Oxprenolol,Trasicor, Slow
D010641 Phenotype The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment. Phenotypes
D011110 Polymorphism, Genetic The regular and simultaneous occurrence in a single interbreeding population of two or more discontinuous genotypes. The concept includes differences in genotypes ranging in size from a single nucleotide site (POLYMORPHISM, SINGLE NUCLEOTIDE) to large nucleotide sequences visible at a chromosomal level. Gene Polymorphism,Genetic Polymorphism,Polymorphism (Genetics),Genetic Polymorphisms,Gene Polymorphisms,Polymorphism, Gene,Polymorphisms (Genetics),Polymorphisms, Gene,Polymorphisms, Genetic
D004359 Drug Therapy, Combination Therapy with two or more separate preparations given for a combined effect. Combination Chemotherapy,Polychemotherapy,Chemotherapy, Combination,Combination Drug Therapy,Drug Polytherapy,Therapy, Combination Drug,Chemotherapies, Combination,Combination Chemotherapies,Combination Drug Therapies,Drug Polytherapies,Drug Therapies, Combination,Polychemotherapies,Polytherapies, Drug,Polytherapy, Drug,Therapies, Combination Drug
D005260 Female Females
D005500 Follow-Up Studies Studies in which individuals or populations are followed to assess the outcome of exposures, procedures, or effects of a characteristic, e.g., occurrence of disease. Followup Studies,Follow Up Studies,Follow-Up Study,Followup Study,Studies, Follow-Up,Studies, Followup,Study, Follow-Up,Study, Followup
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man

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