Trandate Mechanism of Action





Zuellig Pharma
Full Prescribing Info
ATC Code: C07AG01.
Pharmacodynamics: Mechanism of Action: Labetalol lowers blood pressure by blocking peripheral arteriolar alpha-adrenoceptors, thus reducing peripheral resistance, and by concurrent beta-blockade, protects the heart from reflex sympathetic drive that would otherwise occur.
Pharmacodynamic Effects: Cardiac output is not significantly reduced at rest or after moderate exercise. Increases in systolic blood pressure during exercise are reduced but corresponding changes in diastolic pressure are essentially normal. All these effects would be expected to benefit hypertensive patients.
Tablet: In patients with angina pectoris coexisting with hypertension, the reduced peripheral resistance decreases myocardial afterload and oxygen demand. All these effects would be expected to benefit hypertensive patients and those with coexisting angina.
Clinical Studies: No information is available.
Pharmacokinetics: Absorption: Tablet: Labetalol chemically consists of four stereoisomers with different pharmacodynamics effect. Labetalol is rapidly absorbed from the gastrointestinal tract with peak plasma levels occurring 1 to 2 h after oral administration. There is a significant first-pass metabolism leading to a bioavailability of approximately 25%, but there is considerable variation. The bioavailability of labetalol is increased in elderly subjects.
Distribution: About 50% of labetalol in the blood is protein bound. Only negligible amounts of labetalol cross the blood brain barrier in animal studies. Labetalol crosses the placental barrier and is secreted in breast milk.
Biotransformation: Labetalol is metabolised mainly through conjugation to inactive glucuronide metabolites.
Elimination: The glucuronide metabolites are excreted both in the urine and via the bile, into the faeces. Less than 5% of the labetalol dose is excreted unchanged in urine and bile. The plasma half-life of labetalol is about 4 h.
Special Patient Populations: Hepatic Impairment: Labetalol undergoes significant but variable first-pass metabolism when given by the oral route. In a study of 10 patients with histologically proven cirrhosis, exposure to oral labetalol was increased approximately three-fold compared with healthy controls. Inter-subject variability in both patients and controls was high (approximately 2.5-fold). Patients with hepatic impairment may require lower oral doses of labetalol (see Dosage & Administration and Precautions).
Toxicology: Non-Clinical Information: Carcinogenesis, mutagenesis and teratogenesis: There was no evidence of mutagenic potential from in vitro and in vivo tests.
Labetalol showed no evidence of carcinogenicity in long-term studies performed in mice and rats.
No teratogenicity was observed in rats and rabbits at oral doses 6 and 4 times the maximum recommended human dose, respectively. Increased foetal resorptions were seen in both species at doses approximating the maximum recommended human dose. A teratology study performed with labetalol in rabbits at intravenous doses up to 1.7 times the maximum recommended human dose revealed no evidence of drug-related harm to the foetus.
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