Lemildipine

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Lemildipine is a calcium channel blocker of the dihydropyridine class, primarily used in the management of hypertension and angina pectoris. It functions by inhibiting the influx of calcium ions through L-type calcium channels, which are predominantly found in the vascular smooth muscle and cardiac muscle. This action results in the relaxation of vascular smooth muscle, leading to vasodilation and a subsequent decrease in blood pressure.

Pharmacology

Lemildipine is a selective L-type calcium channel antagonist. By blocking these channels, it reduces intracellular calcium concentrations, which is crucial for muscle contraction. The reduction in calcium availability leads to relaxation of the vascular smooth muscle, particularly in the arterioles, thereby reducing peripheral vascular resistance and lowering blood pressure.

Mechanism of Action

Lemildipine binds to the alpha-1 subunit of the L-type calcium channels located on the cell membrane of vascular smooth muscle cells. This binding inhibits the transmembrane influx of calcium ions into these cells, which is necessary for the contraction of the smooth muscle. The inhibition of calcium entry results in vasodilation, particularly in the peripheral arterioles, and decreases the total peripheral resistance.

Pharmacokinetics

Lemildipine is well absorbed from the gastrointestinal tract, but it undergoes significant first-pass metabolism in the liver, resulting in a bioavailability of approximately 30-40%. It is highly protein-bound in the plasma, primarily to albumin. The drug is metabolized in the liver by the cytochrome P450 enzyme system, particularly CYP3A4, and is excreted primarily in the urine as inactive metabolites.

Clinical Use

Lemildipine is indicated for the treatment of hypertension and chronic stable angina. It may be used alone or in combination with other antihypertensive agents. The typical starting dose is 5 mg once daily, which may be increased to 10 mg once daily depending on the patient's response and tolerability.

Adverse Effects

Common side effects of lemildipine include headache, dizziness, flushing, and peripheral edema. These effects are generally mild and tend to diminish with continued use. Rare but serious adverse effects include hypotension, bradycardia, and heart block.

Contraindications

Lemildipine is contraindicated in patients with known hypersensitivity to dihydropyridine calcium channel blockers. Caution is advised in patients with severe aortic stenosis, unstable angina, or severe hypotension.

Drug Interactions

Lemildipine may interact with other medications that affect the cytochrome P450 system, particularly CYP3A4 inhibitors and inducers. Co-administration with other antihypertensive agents may potentiate the blood pressure-lowering effects.

Also see

• Calcium channel blocker
• Hypertension
• Angina pectoris
• Dihydropyridine
• L-type calcium channel