| Indication | For the management of hypertension (alone or in combination with other classes of antihypertensive agents), as well as chronic stable angina pectoris and sympathetic overactivity syndrome associated with severe tetanus. Labetalol is used parenterally for immediate reduction in blood pressure in severe hypertension or in hypertensive crises when considered an emergency, for the control of blood pressure in patients with pheochromocytoma and pregnant women with preeclampsia, and to produce controlled hypotension during anesthesia to reduce bleeding resulting from surgical procedures. |
| Pharmacodynamics | Labetalol is an selective alpha-1 and non-selective beta adrenergic blocker used to treat high blood pressure. It works by blocking these adrenergic receptors, which slows sinus heart rate, decreases peripheral vascular resistance, and decreases cardiac output. Labetalol has two asymmetric centers and therefore, exists as a molecular complex of two diastereoisomeric pairs. Dilevalol, the R,R' stereoisomer, makes up 25% of racemic labetalol. |
| Mechanism of action | Labetalol HCl combines both selective, competitive, alpha-1-adrenergic blocking and nonselective, competitive, beta-adrenergic blocking activity in a single substance. In man, the ratios of alpha- to beta- blockade have been estimated to be approximately 1:3 and 1:7 following oral and intravenous (IV) administration, respectively. The principal physiologic action of labetalol is to competitively block adrenergic stimulation of β-receptors within the myocardium (β1-receptors) and within bronchial and vascular smooth muscle (β2-receptors), and α1-receptors within vascular smooth muscle. This causes a decrease in systemic arterial blood pressure and systemic vascular resistance without a substantial reduction in resting heart rate, cardiac output, or stroke volume, apparently because of its combined α- and β-adrenergic blocking activity. |
| Absorption | Completely absorbed (100%) from the gastrointestinal tract with peak plasma levels occurring 1 to 2 hours after oral administration. The absolute bioavailability of labetalol is increased when administered with food. |
| Volume of distribution | Not Available |
| Protein binding | 50% |
| Metabolism | Primarily hepatic, undergoes significant first pass metabolism |
| Route of elimination | These metabolites are present in plasma and are excreted in the urine, and via the bile, into the feces. |
| Half life | 6-8 hours |
| Clearance | Not Available |
| Toxicity | LD50 = 66 mg/kg (Rat, IV). Side effects or adverse reactions include dizziness when standing up, very low blood pressure, severely slow heartbeat, weakness, diminished sexual function, fatigue |