Source: Υπουργείο Υγείας (CY) Revision Year: 2020 Publisher: Remedica Ltd, Aharnon Str., Limassol Industrial Estate, 3056 Limassol, Cyprus
Pharmacotherapeutic group: Antihypertensives; Antiadrenergic agents, peripherally acting
ATC code: C02CA01
Prazosin causes a decrease in total peripheral vascular resistance through selective inhibition of postsynaptic alpha-1-adrenoreceptors in vascular smooth muscle. The results of the forearm plenthysmographic studies in humans demonstrate that the resultant peripheral vasodilation is a balanced effect on both resistance vessels (arterioles) and capacitance vessels (veins).
In hypertensive patients, blood pressure is lowered in both the supine and standing positions; this effect is more pronounced on the diastolic blood pressure. Tolerance to the antihypertensive effect has not been observed in long-term clinical use; relatively little tachycardia or change in renin levels has been noted. Rebound elevation of blood pressure does not occur following abrupt cessation of prazosin therapy.
The therapeutic efficacy of prazosin in patients with congestive heart failure is ascribed to a reduction in left ventricular filling pressure, reduction in cardiac impedance and an augmentation of cardiac output. The use of prazosin in congestive heart failure does not provoke a reflex tachycardia and blood pressure reduction is minimal in normotensive patients.
Prazosin has been found to successfully reduce the severity of the signs, symptoms, frequency and duration of attacks, in patients with Raynaud’s disease.
In low dosage, antagonism of alpha-1-receptors on prostatic and urethral smooth muscle has been shown to improve the urinary pressure profile in men and to improve symptoms of benign prostatic hyperplasia.
Clinical studies have shown that prazosin therapy is not associated with adverse changes in the serum lipid profile.
Following oral administration in normal volunteers and hypertensive patients plasma concentrations of prazosin reach a peak in one or two hours with a plasma half-life of two to three hours. Pharmacokinetic data in a limited number of patients with congestive heart failure, most of whom showed evidence of hepatic congestion, indicates that peak plasma concentrations are reached in 2.5 hours and plasma half life is approximately 7 hours. Prazosin is highly bound to plasma protein. Studies indicate that prazosin is extensively metabolised, primarily by demethylation and conjugation, and excreted mainly via bile and faeces.
Renal blood flow and glomerular filtration rate are not impaired by long term oral administration and thus prazosin can be used with safety in hypertensive patients with impaired renal function.
Prazosin hydrochloride was not mutagenic in genetic toxicology testing, and was not carcinogenic in an 18-month study conducted in rats.
In chronic studies (one year or more) conducted with prazosin hydrochloride in rats and dogs, testicular changes consisting of atrophy and necrosis occurred at 25 mg/kg/day (75 times the usual maximum recommended human dose), while no such changes were observed in either species at a dose of 10 mg/kg/day (30 times the usual maximum recommended human dose).
In a reproductive toxicology study conducted in rats with prazosin hydrochloride, a decrease in fertility occurred in both males and females at a dose of 75 mg/kg/day (225 times the usual maximum recommended human dose), while animals given 25 mg/kg/day (75 times the usual maximum recommended human dose) were unaffected.
Prazosin hydrochloride was not teratogenic in rats and rabbits up to the highest dose tested of 75 mg/kg, which is 225 times the usual maximum recommended human dose.
Although no teratogenic effects were seen in animal testing, the safety of prazosin during pregnancy has not been established. The use of prazosin and a beta-blocker for the control of severe hypertension in 44 pregnant women revealed no drug-related foetal abnormalities or adverse effects. Therapy with prazosin was continued for as long as 14 weeks.
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