Lodipine (Lacidipine)

Uses

Lodipine (Lacidipine) is used for the treatment of hypertension either alone or in combination with other antihypertensive agents, including ß-blockers, diuretics, ACE-inhibitors etc.

Lodipine (Lacidipine) is also used to associated treatment for these conditions: High Blood Pressure (Hypertension)

How Lodipine (Lacidipine) works

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. Lodipine (Lacidipine) 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 . Lodipine (Lacidipine) 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 .

Dosage

Lodipine (Lacidipine) dosage

The recommended initial dose of Lodipine (Lacidipine) is 2 mg once daily. The dose may be increased to 4 mg and then, if necessary, to 6 mg after 3 to 4 weeks. Lodipine (Lacidipine) should be taken preferably in the morning.

Side Effects

Lodipine (Lacidipine) is generally well tolerated. Some individuals may experience minor side effects like flushing, palpitation, edema, headache, dizziness, rarely gastro-intestinal disturbances, gum hyperplasia, mood disturbances, asthenia, polyuria, muscle cramps, skin rash etc.

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 .

Precaution

Cardiac conduction abnormalities, poor cardiac reserves, hepatic impairment, withdraw if ischemic pain occurs shortly after initiating treatment or if cardiogenic shock develops, avoid grape fruit juice.

Interaction

The plasma concentration of Lodipine (Lacidipine) may be increased by simultaneous administration of cimetidine. No specific pharmacodynamic interaction problems have been identified in studies with common antihypertensive agents or with digoxin, tolbutamide or warfarin.

Elimination Route

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 .

Half Life

The average terminal half-life of lacidipine ranges from between 13 and 19 hours at steady state .

Elimination Route

Approximately 70% of the administered dose is eliminated as metabolites in the faeces and the remainder as metabolites in the urine .

Pregnancy & Breastfeeding use

Pregnancy: There are no data on the safety of Lodipine (Lacidipine) in human pregnancy. Lodipine (Lacidipine) provides no evidence of a teratogenic effect in animal study.

Lactation: Milk transfer studies in animals have shown that Lodipine (Lacidipine) (or its metabolites) are likely to be excreted into breast milk. There is, however, no clinical experience of Lodipine (Lacidipine) in pregnancy and lactation. Accordingly, Lodipine (Lacidipine) should not be used during pregnancy or lactation.

Contraindication

Hypersensitivity to any ingredient of this product, cardiogenic shock, unstable angina, aortic stenosis, avoid within 1 month of myocardial infarction, impaired left ventricular function.

Special Warning

Use in Neonates: There are no data on safety or efficacy of Lodipine (Lacidipine) in neonates.

Use in children: Treatment with Lodipine (Lacidipine) have not been evaluated in Children.

Hepatic Impairment: Severe: Reduce dose.

Acute Overdose

Symptoms: Prolonged peripheral vasodilation associated with hypotension and tachycardia, bradycardia or prolonged AV conduction.

Management: Symptomatic and supportive treatment.

Storage Condition

Store in a cool and dry place, protect from light and moisture. Keep out of the reach of children.

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