Introduction
Lacitab Tablet 2 mg is a highly lipophilic dihydropyridine calcium channel blocker used as an antihypertensive agent. It relaxes vascular smooth muscle, dilates peripheral arterioles, and lowers blood pressure with a slow onset and long duration of action, minimizing reflex tachycardia. Its high lipophilicity allows it to accumulate within cell membranes, contributing to its prolonged clinical half-life. Compared with other dihydropyridine calcium channel blockers, lacidipine also exhibits greater antioxidant activity, which may provide additional antiatherosclerotic benefits. Clinical studies have shown antihypertensive efficacy comparable to other long-acting calcium channel blockers, thiazide diuretics, beta-blockers, and ACE inhibitors. It is available as once-daily oral tablets.
Uses
Lacitab Tablet 2 mg is a lipophilic dihydropyridine calcium channel blocker with a slow onset of action used to treat hypertension.
Indicated for the treatment of hypertension either alone or in combination with other antihypertensive agents, including β-adrenoceptor antagonists, diuretics, and ACE-inhibitors .
Associated Conditions
Pharmacodynamics
acidipine is a specific and potent calcium antagonist with a predominant selectivity for calcium channels in the vascular smooth muscle. Its main action is to dilate predominantly peripheral and coronary arteries, reducing peripheral vascular resistance and lowering blood pressure .
Following the oral administration of 4 mg lacidipine to volunteer subjects, a minimal prolongation of QTc interval has been observed (mean QTcF increase between 3.44 and 9.60 ms in young and elderly volunteers) .
Mechanism of Action
By blocking the voltage-dependent L-type calcium channels, it prevents the transmembrane calcium influx . Normally, calcium ions serve as intracellular messengers or activators in exictable cells including vascular smooth muscles. The influx of calcium ultimately causes the excitation and depolarization of the tissues. Lacitab Tablet 2 mg inhibits the contractile function in the vascular smooth muscle and reduce blood pressure. Due to its high membrane partition coefficient, some studies suggest that lacidipine may reach the receptor via a two-step process; it first binds and accumulates in the membrane lipid bilayer and then diffuses within the membrane to the calcium channel receptor . It is proposed that lacidipine preferentially blocks the inactivated state of the calcium channel .
Through its antioxidant properties shared amongst other dihydropyridine calcium channel blockers, lacidipine demonstrates an additional clinical benefit. Its antiatherosclerotic effects are mediated by suppressing the formation of reactive oxygen species (ROS) and subsequent inflammatory actions by chemokines, cytokines and adhesion molecules, thus reducing atherosclerotic lesion formation . Lacitab Tablet 2 mg may also suppress cell proliferation and migration in smooth muscle cells and suppress the expression of matrix metalloproteinases, which affects the stability of atheromatous plaques .
Absorption
Since it is a highly lipophilic compound, lacidpine is rapidly absorbed from the gastrointestinal tract following oral administration with the peak plasma concentrations reached between 30 and 150 minutes of dosing . The peak plasma concentrations display large interindividual variability, with the values ranging from 1.6 to 5.7 μg/L following single-dose oral administration of lacidipine 4mg in healthy young volunteers .
Absolute bioavailability is less than 10% due to extensive first-pass metabolism in the liver .
Protein Binding
Lacitab Tablet 2 mg is highly protein-bound (more than 95%) to predominantly albumin and to a lesser extent, alpha-1-glycoprotein .
Route of Elimination
Approximately 70% of the administered dose is eliminated as metabolites in the faeces and the remainder as metabolites in the urine .
Half Life
The average terminal half-life of lacidipine ranges from between 13 and 19 hours at steady state .
Toxicity
There have been no recorded cases of lacidipine tablets overdosage. Some of the symptoms of overdose include prolonged peripheral vasodilation associated with hypotension and tachycardia. Bradycardia or prolonged AV conduction could theoretically occur. As there is no known antidote for lacidipine, the use of standard general measures for monitoring cardiac function and appropriate supportive and therapeutic measures is recommended .
Oral LD50 in mouse, rabbit and rat are 300mg/kg, 3200mg/kg and 980mg/kg, respectively .
