High Blood Pressure / Hypertension

β-Blockers

By Cardiologist on June 2nd, 2010

The exact hypotensive mechanism of β-blockers is not known but may involve decreased cardiac output through negative chronotropic and inotropic effects on the heart and inhibition of renin release from the kidney.

Even though there are important pharmacodynamic and pharmacokinetic differences among the various β-blockers, there is no difference in clinical antihypertensive efficacy.

Atenolol, betaxolol, bisoprolol, and metoprolol are cardioselective at low doses and bind more avidly to β₁-receptors than to β₂-receptors. As a result, they are less likely to provoke bronchospasm and vasoconstriction and may be safer than nonselective β-blockers in patients with asthma, chronic obstructive pulmonary disease, diabetes, and PAD. Cardioselectivity is a dose-dependent phenomenon, and the effect is lost at higher doses.

Acebutolol, carteolol, penbutolol, and pindolol possess intrinsic sympathomimetic activity (ISA) or partial β-receptor agonist activity. When sympathetic tone is low, as in resting states, β-receptors are partially stimulated, so resting heart rate, cardiac output, and peripheral blood flow are not reduced when receptors are blocked. Theoretically, these drugs may have advantages in patients with heart failure or sinus bradycardia. Unfortunately, they do not reduce CV events as well as other β-blockers and may increase risk after MI or in those with high coronary disease risk. Thus, agents with ISA are rarely needed.

There are pharmacokinetic differences among β-blockers in first-pass metabolism, serum half-lives, degree oflipophilicity, and route of elimination. Propranolol and metoprolol undergo extensive first-pass metabolism. Atenolol and nadolol have relatively long half-lives and are excreted renally; the dosage may need to be reduced in patients with moderate to severe renal insufficiency. Even though the half-lives of the other β-blockers are much shorter, once-daily administration still maybe effective. β-Blockers vary in their lipophilic properties and thus CNS penetration.

Side effects from β-blockade in the myocardium include bradycardia, AV conduction abnormalities, and acute heart failure. Blocking β₂-receptors in arteriolar smooth muscle may cause cold extremities and aggravate PAD or Raynaud’s phenomenon because of decreased peripheral blood flow.

Abrupt cessation of β-blocker therapy may produce unstable angina, MI, or even death in patients with coronary disease. In patients without heart disease, abrupt discontinuation of β-blockers may be associated with tachycardia, sweating, and generalized malaise in addition to increased blood pressure. For these reasons, it is always prudent to taper the dose gradually over 1 to 2 weeks before discontinuation.

Increases in serum lipids and glucose appear to be transient and of little clinical importance. β-Blockers increase serum triglyceride levels and decrease high-density lipoprotein cholesterol levels slightly. β-Blockers with α-blocking properties (carvedilol and labetalol) do not affect serum lipid concentrations.

Comments are closed.