Figure 716

Central (^-adrenergic agonists. a-Methyldopa is a methyl-substituted amino acid that is active only after decarboxylation and conversion to ( -methyl-norepinephrine. The antihypertensive effect results from accumulation of ( 2-adrenergic receptors, displacing and competing with endogenous catecholamines. Methyldopa is absorbed poorly (<50%); peak plasma concentrations occur in 2 to 4 hours. It is metabolized in the liver and excreted in the urine mainly as the inactive O-sulfate conjugate. The plasma half-life of methyldopa (1 to 2 hours) and its metabolites is prolonged in patients with renal insufficiency; dose reduction is required.

Clonidine, an imidazoline derivative, acts by stimulating either central ( 2-adrenergic receptors or imidazole receptors. Clonidine may be administered orally or by a transdermal delivery system (TTS). When given orally, it is absorbed well (>75%); peak plasma concentrations occur in 3 to 5 hours. Clonidine is metabolized mainly in the liver; fecal excretion ranges from 15% to 30%, and 40% to 60% is excreted unchanged in the urine. In patients with renal insufficiency, the plasma half-life (12 to 16 hours) may be extended to more than 40 hours; dose reduction is required. When clonidine is administered transdermally, therapeutic plasma levels are achieved within 2 to 3 days.

Guanabenz, a guanidine derivative, is highly selective for central (^-adrenergic receptors. It is absorbed well (>75%); peak plasma levels are reached in 2 to 5 hours. Guanabenz undergoes extensive hepatic metabolism; less than 2% is excreted unchanged in the urine. The plasma half-life (approximately 6 hours) is not prolonged in patients with renal insufficiency.

Guanfacine is a phenylacetyl-guanidine derivative with a longer plasma half-life than guanabenz. It is absorbed well (>90%); peak plasma concentrations are reached in 1 to 4 hours. The drug is primarily metabolized in the liver. Guanfacine and its metabolites are excreted primarily by the kidneys; 24% to 37% is excreted as unchanged drug in the urine. The plasma half-life (15 to 17 hours) is not prolonged in patients with renal insufficiency [6,9].

THE SIDE EFFECT PROFILE OF CENTRAL «¡»-ADRENERGIC AGONISTS

The side effect profile of central (^-adrenergic agonists. The side effect profile of these agents is diverse [6,9].

Side effects

Mechanisms

Sedation/drowsiness

Stimulation of a2-adrenergic receptors in

Blood Pressure Health

Blood Pressure Health

Your heart pumps blood throughout your body using a network of tubing called arteries and capillaries which return the blood back to your heart via your veins. Blood pressure is the force of the blood pushing against the walls of your arteries as your heart beats.Learn more...

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