Posted by Lee M. on April 20, 1999 at 19:33:25:
In Reply to: A new medicine posted by Dion Carlo Tretta on April 20, 1999 at 17:04:20:
Here is a shory description I found on Clinical Pharmacology Online.
Description: Atenolol is a competitive, beta1-selective adrenergic antagonist, similar to metoprolol. Atenolol has a longer plasma half-life than does metoprolol, which may allow for less frequent dosing. As with all "selective" beta-blockers, high doses result in attenuated or lost selectivity for the beta1-receptor. Unlike pindolol, atenolol does not have intrinsic sympathomimetic properties. Atenolol also does not possess membrane-stabilizing activity as pindolol and propranolol do. In addition, atenolol has the lowest lipid solubility within the class, which affects its route of elimination and, theoretically, its potential for causing CNS side effects. Atenolol was approved by the FDA in 1981.
Mechanism of Action: Beta-adrenergic antagonists counter the effect of sympathomimetic neurotransmitters (i.e., catecholamines) by competing for receptor sites. Similar to metoprolol, atenolol, in low doses, selectively blocks sympathetic stimulation mediated by beta1-adrenergic receptors in the heart and vascular smooth muscle. The pharmacodynamic consequences of this activity include: reduction of resting heart rate and, subsequently, cardiac output; reduction of both systolic and diastolic blood pressure at rest and with exercise; and possible reduction of reflex orthostatic hypotension. With higher doses (>100 mg/day), atenolol also competitively blocks beta2-adrenergic responses in the bronchial and vascular smooth muscles. In addition, serum free fatty acid concentrations are decreased and triglyceride levels increased by atenolol.
A critical effect of beta blockade is to provide prophylaxis and reduction in myocardial ischemia and potentially prevent the severity of subsequent myocardial infarction. Part of this effect also may be attributed to the antiarrhythmic properties of beta blockade at the nodal level of pacemaker control.
Actions that make atenolol useful in treating hypertension include: a negative chronotropic effect that decreases heart rate at rest and after exercise; a negative inotropic effect that decreases cardiac output; reduction of sympathetic outflow from the CNS; and suppression of renin release from the kidneys. Thus, atenolol, like other beta-blockers, affects blood pressure via multiple mechanisms. In general, beta-blockers without intrinsic sympathomimetic activity (ISA) exert detrimental effects on LVH and the lipid profile, and cause sexual dysfunction.
Atenolol is used to treat angina because the drug decreases the oxygen demand of the heart, both by decreasing heart rate and contractility and by lowering blood pressure. However, in patients with cardiac failure, the opposite may be true (i.e., the drug can increase the oxygen demand of the heart.)
Atenolol possesses numerous mechanisms that may contribute to its efficacy in preventing migraine headaches.[350] Beta-blockade can prevent arterial dilation, inhibit renin secretion, and block catecholamine-induced lipolysis. Blocking lipolysis, decreases arachidonic acid synthesis and subsequent prostaglandin production. Inhibition of platelet aggregation is due to this decrease in prostaglandins and blockade of catecholamine-induced platelet adhesion. Other actions include increased oxygen delivery to tissues and prevention of coagulation during epinephrine release.
Pharmacokinetics: After oral administration of atenolol, about 50—60% of the dose is rapidly absorbed. The onset of heart rate reduction occurs in about 1 hour, with the peak effect achieved within 2—4 hours. The duration of action is roughly 24 hours. After parenteral administration, the peak effect is seen in 5 minutes and lasts less than 12 hours. Effects on blood pressure do not coincide with effects on heart rate, nor does the antihypertensive effect exhibit a linear dose/pharmacodynamic response.
Atenolol is distributed throughout the body and into breast milk. It also crosses the placenta, with fetal serum atenolol concentrations approaching those of the mother. Unlike propranolol, atenolol distribution into the CNS by crossing the blood-brain barrier is minimal. Atenolol is minimally bound to plasma proteins, averaging only 10%, which, along with it low lipophilicity, may explain some of its distribution characteristics.
The serum half-life of atenolol in patients with normal renal function is 6—7 hours in adults and about 4.6 hours in children. Half-life increases progressively as renal function worsens, and, although dosing should be conservative in patients with renal failure, atenolol has been given safely to these patients. Minimal, if any, metabolism occurs in the liver, and 40—50% of an oral dose is excreted renally as unchanged drug. The rest of the dose is excreted via the fecal route as unchanged drug. It is important to note that atenolol is removed by hemodialysis, so supplemental doses may be required following this procedure.
[Revised 12/30/1997]
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