Pencor Mechanism of Action

Pharmacotherapeutic group: Antihypertensive/Benign Prostatic Hyperplasia Therapy Agent.
Pharmacology: Doxazosin has a selective postsynaptic alpha1-adrenergic blocking action, which is thought to account primarily for its effects.
Hypertension: Blockade of alpha1-adrenergic receptors by Doxazosin results in peripheral vasodilation, which produces a fall in blood pressure because of decreased peripheral vascular resistance.
Benign prostatic hyperplasia: Relaxation of smooth muscle in the bladder neck, prostate, and prostate capsule produced by alpha1-adrenergic blockade results in reduction in urethral resistance and pressure, bladder outlet resistance, and urinary symptoms. Doxazosin slightly lowers the levels of total cholesterol, low-density lipoprotein (LDL) cholesterol, and triglycerides. In addition, Doxazosin slightly increases high-density lipoprotein (HDL) cholesterol and the HDL/ total cholesterol ratio. These lipid effects appear to be result of Doxazosin's effect on lipid metabolism (i.e., increasing LDL receptor activity, decreasing intracellular LDL cholesterol synthesis, decreasing synthesis and secretion of very low-density lipoprotein [VLDL] cholesterol, stimulation of liproprotein lipase activity, and decreasing the rate of cholesterol absorption). However, the implications of these changes are unclear.
Pharmacokinetics: Absorption: Well-absorbed from gastrointestinal tract; bioavailability is about 65%.
Protein binding: Very high (98 to 99%).
Biotransformation: Metabolized extensively in the liver. Although several active and inactive metabolites have been identified (2-piperazinyl, 6' and 7'-hydroxy, 6' and 7'-O-desmethyl, and 2-amino), there is no evidence that they are present in substantial amounts.
Half-life: Elimination: 19 to 22 hours; does not appear to be significantly influence by age or mild to moderate renal impairment.
Onset of action: Hypertension: 1 to 2 hours; there is a slight initial fall in blood pressure within the first hour, but the main hypotensive effect is apparent from 2 hours onwards. Benign prostatic hyperplasia (BPH): Within 1 to 2 weeks.
Time to peak effect: Antihypertensive: single dose: 2 to 6 hours.
Duration of action: Antihypertensive: single dose: 24 hours.
Elimination: Fecal: Unchanged drug, about 5% metabolites, 63 to 65%. Renal: 9%. In dialysis: Doxazosin is not removed by hemodialysis.