Pharmacological properties : תכונות פרמקולוגיות

Pharmacodynamic Properties

5.1.   Pharmacodynamic properties

Pharmacotherapeutic group: alpha-adrenoreceptor antagonists
ATC Code: G04CA03

Mechanism of action and Pharmacodynamic effects
Hypertension
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. Hytrin 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 Hytrin administration.
Additionally, the increase in total cholesterol seen with other hypertensive agents did not occur when these were used in combination with Hytrin.

Benign Prostatic Hyperplasia
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.
Clinical efficacy and safety
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.

Pharmacokinetic Properties

5.2.   Pharmacokinetic properties

Absorption
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.

Distribution
Approximately 90-94% of terazosin is bound to plasma proteins. Protein binding is independent of total active substance concentrations.

Biotransformation
Main metabolites of terazosin are caused by demethylation and conjugation.

Elimination
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.

Linearity / non-linearity of pharmacokinetics
After oral dosing of terazosin AUC and Cmax increase in proportion with dose over the recommended dose range (2-10 mg).