Therabloc Mechanism of Action

Cardioselective β-blocker.
Pharmacology: Atenolol is a β₁-selective adrenergic-blocking agent. It competitively blocks adrenergic stimulation of β₁-adrenergic receptors within the myocardium and vascular smooth muscle. Low doses of atenolol selectively inhibit cardiac and lipolytic β₁-receptors but with little effect on the β₂-adrenergic receptors of bronchial and vascular smooth muscle. At high doses (ie, >100 mg daily), this selectivity of atenolol for β₁-adrenergic receptors may diminish and the drug may competitively block β₁- and β₂-adrenergic receptors. Atenolol does not exhibit any intrinsic sympathomimetic activity nor any membrane-stabilizing activity.
By inhibiting myocardial β₁-adrenergic receptors, atenolol produces negative-chronotropic and negative-inotropic effects. The negative-chronotropic action of atenolol on the sinoatrial (SA) node results in a decrease in the rate of SA node discharge and an increase in recovery time, thereby decreasing resting and exercise-stimulated heart rate and reflex orthostatic node. Therefore, high doses of atenolol may produce sinus arrest or AV block especially in patients with sick-sinus syndrome. Although stroke index may be increased moderately by about 10%, atenolol usually reduces cardiac output by about 20%, probably secondary to its effect on heart rate. The decrease in myocardial contractility and heart rate, as well as the reduction in myocardial oxygen consumption accounts for the effectiveness of the drug in chronic stable angina pectoris. However, in cardiac failure, atenolol can increase oxygen requirements by increasing left ventricular fiber length and end-diastolic pressure.
Pharmacokinetics: Absorption: Atenolol is rapidly but incompletely absorbed from the gastrointestinal tract. Approximately 50-60% of an oral dose is absorbed. In healthy adults, peak plasma concentrations of 1-2 mcg/mL are achieved after oral administration of a single 200-mg dose of atenolol. An approximately 4-fold interindividual variation in plasma concentrations attained has been reported with a specific oral dose of atenolol. The effect of atenolol on heart rate usually has an onset of 1 hr, peaks 2-4 hrs and persists for 24 hrs. The antihypertensive effect of a single oral dose usually persists for 24 hrs. Atenolol's effect on heart rate, but not on blood pressure, correlates linearly with plasma atenolol concentrations of 0.02-200 mcg/mL.
Distribution: In animals, atenolol is well distributed into most tissues and fluids except brain and CSF. Unlike propranolol, only a small amount of atenolol is distributed into the CNS.
Approximately 6-16% of atenolol is bound to plasma protein.
Atenolol readily crosses the placenta and during continuous administration, fetal serum concentrations of the drug are probably equivalent to those in maternal serum. Atenolol is distributed into milk. The extent of distribution of atenolol into milk has not been clearly determined, but the amount of drug a nursing infant would ingest is believed to be too small to be clinically significant.
Elimination: In patients with normal renal function, atenolol has a plasma t_½ of 6-7 hrs. Plasma t_½ of the drug increases to 16-27 hrs in patients with creatinine clearances of 15-35 mL/min/1.73 m² and exceeds 27 hrs with progressive renal impairment. Little or no metabolism of atenolol occurs in the liver. Approximately 40-50% of an oral dose of the drug is excreted unchanged in urine. The remainder is excreted unchanged in feces, principally as unabsorbed drug.