Influence of dosage and dietary sodium on the first-dose effects of prazosin.

Abstract

Wales 2000 G S STOKES, MD, FRACP, cardiorenal physician R M GRAHAM, MB, BS, fellow in cardiorenal diseases J M GAIN, SRN, SRM, research nurse P R DAVIS, MB, BS, registrar occurred in five out of seven patients given 2 mg prazosin and in two out of four given a 05-mg dose, whereas those taking 2 mg or 0 5 mg and a 250-mmol sodium intake experienced no postural symptoms. These findings indicate that particular care should be taken in starting prazosin treatment in sodium-depleted patients.

Studies on the clinical pharmacology of prazosin. I: Cardiovascular, catecholamine and endocrine changes following a single dose.

“…This theory is further supported by the observation that a high sodium diet appears to protect against the development of first dose symptoms (Stokes, Graham, Gain & Davis, 1977).…”

Lack of relationship between debrisoquine oxidation phenotype and the pharmacokinetics and first dose effect of prazosin.

“…This incidence is higher than that reported by others (CSM, 1975;Rosendorff, 1976) probably because of the concurrent use of 3-adrenoceptor antagonists and diuretics, both of which increase the severity of the effect (Elliott et al, 1981;Stokes et al, 1977). 3-adrenoceptor antagonists are likely to be particularly important, as the inability to maintain a reflex tachycardia is linked to the first dose effect in untreated individuals.…”

The management of hypertension.

“…Loss of consciousness occurred in several instances so that a specific effect on cerebral blood flow was suggested, however prazosin does not appear to alter cerebral blood flow (Rutland etal., 1980). This first dose phenomenon shows some dose dependence (Rosendorff, 1976;Stokes et al, 1977). The use of a low commencing dose of 0.5 mg particularly if given just before bed is likely to result in only minimal dizziness, if at all.…”

“…The first dose phenomenon is the occurrence after the first dose, of symptoms of severe postural hypotension (Bendall etal., 1975;Rosendorff, 1976;Stokes et al, 1977). Loss of consciousness occurred in several instances so that a specific effect on cerebral blood flow was suggested, however prazosin does not appear to alter cerebral blood flow (Rutland etal., 1980).…”

“…Certain manoeuvres, besides a low commencing dose, influence the first dose phenomenon. A high sodium diet abolishes the phenomenon while a low sodium diet enhances it (Stokes et al, 1977). The prior administration of a 1-adrenoceptor blocking drug may also increase the fall in blood pressure associated with this first dose phenomenon (Seideman et al, 1982).…”