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Acetylator phenotype and the antihypertensive response to hydralazine
Acta Medica Scandinavica
|April 1, 1975
Summary
This study found that while hydralazine and oxprenolol effectively treat hypertension, acetylator phenotype influences hydralazine dosage. Phenotyping is recommended to optimize treatment and monitor potential toxicity.
Area of Science:
- Pharmacology
- Cardiovascular Medicine
- Clinical Pharmacy
Background:
- Essential hypertension is a prevalent cardiovascular condition requiring effective pharmacotherapy.
- Hydralazine and beta-blockers are commonly used antihypertensive agents.
- Individual variability in drug response necessitates understanding pharmacokinetic and pharmacodynamic factors.
Purpose of the Study:
- To investigate the relationship between acetylator phenotype and the efficacy of combined hydralazine and oxprenolol therapy in essential hypertension.
- To determine if acetylator status influences hydralazine dosage requirements and antihypertensive response.
- To assess the safety and tolerability of this combination therapy over a one-year follow-up period.
Main Methods:
- Twenty-three outpatients with mild to moderate essential hypertension were treated with hydralazine and oxprenolol.
- Patients were phenotyped as slow or rapid acetylators using the sulphamethazine test.
- Plasma hydralazine levels, blood pressure reduction, and side effects were monitored.
Main Results:
- A significant correlation existed between daily hydralazine dose and plasma hydralazine levels in both slow and rapid acetylators.
- Antihypertensive response correlated with plasma hydralazine levels, with slow acetylators showing a greater mean fall in blood pressure.
- Higher hydralazine doses (mg/kg) were required in rapid acetylators to achieve similar blood pressure reduction compared to slow acetylators.
- Minimal side effects were observed during the one-year follow-up.
Conclusions:
- Combined hydralazine and oxprenolol therapy can effectively manage essential hypertension.
- Acetylator phenotype influences hydralazine pharmacokinetics and dose requirements.
- While treatment may be successful without phenotyping, understanding acetylator status is crucial for optimizing hydralazine dosage and monitoring potential toxicity, as beta-blockers may mask warning signs.