Beta-Blockers Pharmacokinetics and Effects Quiz

Beta-Blockers Pharmacokinetics and Effects

• Propranolol reduces heart rate and myocardial contractility by blocking β1 receptors, leading to decreased cardiac output.
• Propranolol has a longer-lasting heart rate reduction compared to its negative inotropic effects, indicating potential distinctions in β1 receptors.
• Simultaneous β2-receptor blockade by propranolol increases peripheral vascular resistance, including coronary vascular resistance.
• Propranolol may paradoxically increase systolic ejection time and ventricular dilatation, raising myocardial oxygen demand, but its oxygen-sparing effects generally outweigh these changes.
• Propranolol exhibits extensive binding to plasma proteins (90-95%), and changes in protein binding can impact its pharmacokinetics.
• Propranolol is primarily cleared from the plasma through hepatic metabolism, with significant individual variation in the extent of hepatic first-pass metabolism.
• Propranolol reduces the clearance of amide local anesthetics by affecting hepatic blood flow and inhibiting liver metabolism, potentially increasing systemic toxicity of certain amide local anesthetics.
• Chronic propranolol treatment reduces pulmonary first-pass uptake of fentanyl, leading to a greater amount of injected fentanyl entering the systemic circulation.
• Nadolol is a non-selective beta-antagonist with a long duration of action and exhibits slow and incomplete absorption from the gastrointestinal tract.
• Pindolol has a shorter elimination half-time but this duration can be prolonged in patients with renal failure.
• Timolol, a nonselective β-adrenergic receptor antagonist, is as effective as propranolol and is administered as eye drops in the treatment of glaucoma.
• Systemic absorption of timolol can cause bradycardia and increased airway resistance, and it has been associated with impaired control of ventilation in neonates.

Beta-Adrenergic Antagonists: Key Facts and Pharmacokinetics

• Beta-adrenergic stimulation in the heart results in positive and negative effects, including increased heart rate, contractility, and conduction, and decreased relaxation, with around 75% of myocardial β receptors being β1 receptors.
• The main action of β1 receptors is in the heart, kidneys, and adipose tissue, leading to increased heart rate, contractility, and conduction.
• Beta-1 blockers target the heart, kidneys, and JG cells, slowing heart rate, treating arrhythmias, and decreasing myocardial oxygen demand.
• Beta-2 blockers, like propranolol, are used to treat variceal bleeding, migraine prophylaxis, and to alleviate tremors.
• The third-generation nonselective beta-blocker, carvedilol, is used for non-decompensated heart failure to decrease myocardial oxygen demand.
• The chemical structure of β-adrenergic antagonists, derived from isoproterenol, determines whether they act as antagonists or agonists at β-adrenergic receptors.
• β-Adrenergic antagonists are categorized into nonselective and cardioselective groups, with varying degrees of selectivity based on dosage and intrinsic sympathomimetic activity.
• Cardioselective β-adrenergic antagonists are suitable for patients with asthma and reactive airway disease due to their reduced impact on peripheral β2 receptors.
• β1-receptor blockade results in reduced heart rate, slower conduction, decreased contractility, increased ability to relax, and reduced ability to initiate electrical impulses, leading to a decrease in myocardial oxygen demand and improved myocardial blood flow.
• β2-receptor blockade can increase the risk of bronchospasm and worsen symptoms of peripheral vascular disease.
• β-Adrenergic antagonists vary in pharmacokinetics, with esmolol having a brief half-time of about 10 minutes and propranolol and nebivolol being highly protein-bound.
• Understanding elimination half-time is crucial in determining dosing intervals, and therapeutic plasma concentrations can vary significantly among these drugs and patients due to various factors.