Clonipress Mechanism of Action

Pharmacology: Pharmacodynamics: Clonidine, an imidazoline derivative, is a central α-adrenergic stimulant that inhibits sympathetic cardio-accelerator and vasoconstrictor centers. Clonidine stimulates peripheral α-adrenergic receptors producing transient vasoconstriction. Stimulation of α-adrenergic receptors in the brain stem results in reduced sympathetic outflow from the central nervous system (CNS) and a decrease in peripheral resistance, renal vascular resistance, heart rate and blood pressure. Renal blood flow and glomerular filtration rate remain essentially unchanged.
Orthostatic effects are mild and infrequent. The drug does not alter normal hemodynamic responses to exercise. Acute studies have demonstrated a moderate reduction (15-20%) of cardiac output and a decrease of peripheral resistance. During long-term therapy, cardiac output tends to return to control values while peripheral resistance remains decreased. The co-administration of a diuretic enhances antihypertensive efficacy of clonidine.
Blood pressure declines within 30-60 min after an oral clonidine dose.
Pharmacokinetics: The peak plasma clonidine level occurs approximately 3-5 hrs after oral dosing, the plasma half-life (t_½) is 12-16 hrs and the elimination t_½ is 6-24 hrs. About 50% of the absorbed dose is metabolized in the liver. The t_½ increases up to 41 hrs in patients with impaired renal function. About 40-60% of the absorbed dose is recovered in the urine as unchanged drug in 24 hrs.