RiteMED Terazosin Mechanism of Action

Pharmacotherapeutic group: Alpha-adrenoreceptor antagonists. ATC Code: G04C A03.
Pharmacology: Pharmacodynamics: Terazosin, the active ingredient of terazosin tablets, is a selective peripheral α₁-adrenergic blocking agent. Its antihypertensive effects may result from postsynaptic α₁-adrenergic blockade, leading to vasodilatation, decreased total peripheral resistance and venous return. Terazosin is a long-acting oral agent that is useful when given once daily to hypertensives. Long-term treatment with terazosin does not usually cause reflex tachycardia; while cardiac output, renal perfusion and glomerular filtration rate hardly become affected.
Although it has no effect on the underlying pathophysiologic mechanism involved in BPH, terazosin has been shown to significantly increase urinary flow rates and decrease outflow obstruction. It is also effective in easing BPH-related symptoms by preventing stimulation of α₁-adrenergic receptors and consequent smooth muscle contractions in the bladder and prostatic urethra. Urodynamic improvement may help reduce urinary tract infection. The medicinal product, however, does not affect the size of the prostate.
A significant antihypertensive effect has been observed 3 hours following oral administration of terazosin. The medicinal product's antihypertensive effect has been reported to persist for 24 hours after oral administration.
Effects of terazosin on cardiovascular morbidity and mortality have not been investigated.
Pharmacokinetics: Absorption: Terazosin is rapidly and almost completely absorbed from the gastrointestinal tract without being affected by food intake. It has a 90% bioavailability.
Onset and duration: Following administration, mean peak serum levels are achieved within approximately 1 to 2 hours. 36 hours following drug intake, terazosin could still be traced in plasma.
Distribution, metabolism and excretion: Terazosin is 90-94% plasma protein-bound. It is extensively metabolised in the liver via hydrolysis, demethylation and dealkylation with five different metabolites identified. The plasma clearance is approximately 80mL/min. Mean elimination half-life of the parent compound is 12 hours. 10% of the orally administered terazosin is excreted unchanged in the urine and 30% as inactive metabolites. Faecal elimination accounts for 55-60% of the oral dose of which 20% is in the form of unchanged terazosin. There are no reports on possible terazosin excretion in breast milk. The elimination of terazosin seems not to be affected by renal function.
Toxicology: Preclinical safety data: Preclinical data reveal no special hazards for humans based on conventional studies of safety pharmacology.
No evidence of a genotoxic effect of terazosin has been reported from in vitro and in vivo investigations of the mutagenic potential of the substance.
Decreased fertility and testicular atrophy were seen in rats at repeated administration of doses a ≥20-30 times higher than the maximum recommended human dose. Foetal resorptions, decreased foetal weights, increased number of supernumerary ribs and decreased post-natal survival were noted in reproductive toxicity studies in rats and rabbits at maternally toxic doses (60-280 times the maximum recommended human dose).
No carcinogenic effect of terazosin was seen in studies in mice or female rats. In male rats, terazosin induced benign adrenal medullary tumours at the highest administered dose corresponding to 175 times the maximum human dose. The clinical relevance of this finding is unknown.