indication

For the treatment of hypertension. It may be used alone or in combination with other antihypertensive agents.

pharmacology

Nisoldipine, a dihydropyridine calcium-channel blocker, is used alone or with an angiotensin-converting enzyme inhibitor, to treat hypertension, chronic stable angina pectoris, and Prinzmetal's variant angina. Nisoldipine is similar to other peripheral vasodilators. Nisoldipine inhibits the influx of extra cellular calcium across the myocardial and vascular smooth muscle cell membranes possibly by deforming the channel, inhibiting ion-control gating mechanisms, and/or interfering with the release of calcium from the sarcoplasmic reticulum. The decrease in intracellular calcium inhibits the contractile processes of the myocardial smooth muscle cells, causing dilation of the coronary and systemic arteries, increased oxygen delivery to the myocardial tissue, decreased total peripheral resistance, decreased systemic blood pressure, and decreased afterload.

mechanism of action

By deforming the channel, inhibiting ion-control gating mechanisms, and/or interfering with the release of calcium from the sarcoplasmic reticulum, Nisoldipine inhibits the influx of extracellular calcium across the myocardial and vascular smooth muscle cell membranes The decrease in intracellular calcium inhibits the contractile processes of the myocardial smooth muscle cells, causing dilation of the coronary and systemic arteries, increased oxygen delivery to the myocardial tissue, decreased total peripheral resistance, decreased systemic blood pressure, and decreased afterload.

biotransformation

Pre-systemic metabolism in the gut wall, and this metabolism decreases from the proximal to the distal parts of the intestine. Nisoldipine is highly metabolized; 5 major urinary metabolites have been identified. The major biotransformation pathway appears to be the hydroxylation of the isobutyl ester. A hydroxylated derivative of the side chain, present in plasma at concentrations approximately equal to the parent compound, appears to be the only active metabolite and has about 10% of the activity of the parent compound. Cytochrome P450 enzymes are believed to play a major role in the metabolism of nisoldipine. The particular isoenzyme system responsible for its metabolism has not been identified, but other dihydropyridines are metabolized by cytochrome P450 IIIA4.

absorption

Relatively well absorbed into the systemic circulation with 87% of the radiolabeled drug recovered in urine and feces. The absolute bioavailability of nisoldipine is about 5%.

half life

7-12 hours

route of elimination

Although 60-80% of an oral dose undergoes urinary excretion, only traces of unchanged nisoldipine are found in urine.

drug interactions

Conivaptan: CYP3A4 Inhibitors (Strong) may increase the serum concentration of Nisoldipine. Avoid concurrent use of nisoldipine with strong inhibitors of CYP3A4, as the combination may lead to substantial increases in nisoldipine concentrations.

Fosphenytoin: Phenytoin decreases the efficiency of nisoldipine

Phenytoin: Phenytoin decreases the efficiency of nisoldipine

Quinupristin: This combination presents an increased risk of toxicity

Telithromycin: Telithromycin may reduce clearance of Nisoldipine. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Nisoldipine if Telithromycin is initiated, discontinued or dose changed.

Thiopental: The CYP3A4 inducer, Thiopental, may increase the metabolism and clearance of Nisoldipine, a CYP3A4 substrate. Monitor for changes in the therapeutic/adverse effects of Nisoldipine if Thiopental is initiated, discontinued or dose changed.

Tipranavir: Tipranavir, co-administered with Ritonavir, may alter the concentration of Nisoldipine. Monitor for efficacy and adverse/toxic effects of Nisoldipine.

Treprostinil: Additive hypotensive effect. Monitor antihypertensive therapy during concomitant use.

Voriconazole: Voriconazole, a strong CYP3A4 inhibitor, may increase the serum concentration of nisoldipine by decreasing its metabolism. Concomitant therapy should be avoided.