Nicardiin Mechanism of Action

Pharmacotherapeutic group: Belongs to the class of dihydropyridine derivative selective calcium-channel blockers with mainly vascular effects. ATC code: C08CA04.
Pharmacology: Mechanism of action: Nicardipine is a second generation slow calcium channel inhibitor and belongs to the phenyl-dihydropyridine group.
Nicardipine has a greater selectivity for L-type calcium channels in vascular smooth muscle than cardiac myocytes. At very low concentrations it inhibits the influx of calcium into the cell. Its action is produced mainly on arterial smooth muscle. This is reflected in relatively large and rapid changes in blood pressure, with minimal inotropic changes in cardiac function (baroreflex effect).
Pharmacodynamic effects: Administered by systemic route, nicardipine is a potent vasodilator which diminishes total peripheral resistance and lowers blood pressure. Heart rate is temporarily increased; as a result of a decrease in after-load, cardiac output is markedly and durably increased.
In humans, the vasodilator action also occurs in both acute dose administration and chronic administration in the large and small arteries, increasing blood flow and improving arterial compliance. Renal vascular resistance is decreased.
Pharmacokinetics: Absorption: Following intravenous administration, Nicardipine is rapidly absorbed showing the time to onset ranging between 5-15 minutes. Peak plasma levels can reach 184 ng/ml and steady state plasma concentrations of 157 ng/ml achieved within 24-48 hours of continuous infusion.
Distribution: Nicardipine is highly protein bound in human plasma over a wide concentration range.
Metabolism: Nicardipine is metabolized by cytochrome P450 3A4. Either a single dose, or administration 3 times daily for 3 days, less than 0.03% of unchanged nicardipine is recovered in the urine in humans after oral or intravenous administration. The most abundant metabolite in human urine is the glucuronide of the hydroxy form, which is formed by the oxidative cleaving of the N-methylbenzyl moiety and the oxidation of the pyridine ring.
Elimination: The elimination profile of the drug following an intravenous dose consists of three phases, with corresponding half-life: distribution 6.4 min, elimination 1.5 hours, terminal elimination 7.9 hours. Clinical offset of action to be approximately 15 minutes.
Renal impairment: There were no significant differences in the principal pharmacokinetic parameters between severe renal dysfunction and normal renal dysfunction.