Chemical formula: C₁₉H₂₅N₅O₄ Molecular mass: 387.433 g/mol PubChem compound: 5401
Although the exact mechanism of the hypotensive action is not established, the relaxation of peripheral blood vessels appears to be produced mainly by competitive antagonism of post-synaptic alpha-adrenoceptors. Terazosin usually produces an initial gradual decrease in blood pressure followed by a sustained antihypertensive action.
Clinical experience indicates that a 2-5% decrease in total cholesterol plasma concentration and a 3-7% decrease in the combined LDLC + VLDLC fraction plasma concentration from pretreatment values are associated with the administration of therapeutic doses of terazosin.
In clinical trials, plasma concentrates of total cholesterol and combined low density and very low density lipoproteins were found to be slightly reduced following terazosin administration. Additionally, the increase in total cholesterol seen with other hypertensive agents did not occur when these were used in combination with terazosin.
Studies suggest that alpha-1-adrenoreceptor antagonism is useful in improving the urodynamics in patients with chronic bladder obstruction such as in benign prostatic hyperplasia (BPH).
The symptoms of BPH are caused mainly by the presence of an enlarged prostate and by the increased smooth muscle tone of the bladder outlet and prostate, which is regulated by alpha-1-adrenergic receptors.
In in-vitro experiments, terazosin has been shown to antagonise phenylephrine-induced contractions of human pro static tissue. In clinical trials terazosin has been shown to improve the urodynamics and symptomatology in patients with BPH.
Terazosin is well absorbed (80-100%). Terazosin has a minimal “first pass” effect and almost the complete dose of terazosin is systematically available. The plasma concentration of the parent drug is a maximum about 1 hour post administration and declines with a half-life of approximately 12 hours. Food has little or no effect on bioavailability.
Approximately 90-94% of terazosin is bound to plasma proteins. Protein binding is independent of total active substance concentrations.
Main metabolites of terazosin are caused by demethylation and conjugation.
Approximately 10% and 20% of orally administered terazosin is excreted as unchanged active substance in urine and in faeces, respectively. Approximately 40% of the administered dose is eliminated in the urine and 60% in the faeces. The drug is highly bound to plasma proteins.
After oral dosing of terazosin AUC and Cmax increase in proportion with dose over the recommended dose range (2-10 mg).
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 ≥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).
In male rats, terazosin induced benign adrenal medullary tumours at the highest administered dose corresponding to 175 times the maximum human dose.
In male rats, terazosin induced benign adrenal medullary tumours at the highest administered dose corresponding to 175 times the maximum human dose. No such occurrences were seen in female rats or in a similar study in mice. The relevance of these findings with respect to the clinical use of the drug in man is unknown.
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