Zadipina
Zadipina - General Information
A dihydropyridine calcium channel antagonist that acts as a potent arterial vasodilator and antihypertensive agent. It is also effective in patients with cardiac failure and angina. [PubChem]
Pharmacology of Zadipina
Zadipina, 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. Zadipina is similar to other peripheral vasodilators. Zadipina 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.
Zadipina for patients
SULAR is an extended release tablet and should be swallowed whole. Tablets should not be chewed, divided or crushed. SULAR should not be administered with a high fat meal. Grapefruit juice, which has been shown to increase significantly the bioavailability of nisoldipine and other dihydropyridine type calcium channel blockers, should not be taken with SULAR.
Zadipina Interactions
A 30 to 45% increase in AUC and Cmax of nisoldipine was observed with concomitant administration of cimetidine 400 mg twice daily. Ranitidine 150 mg twice daily did not interact significantly with nisoldipine (AUC was decreased by 15-20 %). No pharmacodynamic effects of either histamine H2 receptor antagonist were observed.
Coadministration of phenytoin with 40 mg SULAR tablets in epileptic patients lowered the nisoldipine plasma concentrations to undetectable levels. Coadministration of SULAR with phenytoin or any known CYP3A4 inducer should be avoided and alternative antihypertensive therapy should be considered. Pharmacokinetic interactions between nisoldipine and beta-blockers (atenolol, propranolol) were variable and not significant. Propranolol attenuated the heart rate increase following administration of immediate release nisoldipine. The blood pressure effect of SULAR tended to be greater in patients on atenolol than in patients on no other antihypertensive therapy. Quinidine at 648 mg bid decreased the bioavailability (AUC) of nisoldipine by 26%, but not the peak concentration. The immediate release, but not the coat-core formulation of nisoldipine increased plasma quinidine concentrations by about 20%. This interaction was not accompanied by ECG changes and its clinical significance is not known. No significant interactions were found between nisoldipine and warfarin or digoxin.
Zadipina Contraindications
SULAR is contraindicated in patients with known hypersensitivity to dihydropyridine calcium channel blockers.
Additional information about Zadipina
Zadipina Indication: For the treatment of hypertension. It may be used alone or in combination with other antihypertensive agents.
Mechanism Of Action: By deforming the channel, inhibiting ion-control gating mechanisms, and/or interfering with the release of calcium from the sarcoplasmic reticulum, Zadipina 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.
Drug Interactions: Not Available
Food Interactions: Do not take with grapefruit juice as this has been shown to interfere with nisoldipine metabolism, resulting in a mean increase in Cmax of about 3-fold (up to about 7-fold) and AUC of almost 2-fold (up to 5-fold).
Generic Name: Nisoldipine
Synonyms: Nisoldipinum [Inn-Latin]; Nisoldipino [Inn-Spanish]; Nisoldipin
Drug Category: Vasodilator Agents; Antihypertensive Agents
Drug Type: Small Molecule; Approved
Other Brand Names containing Nisoldipine: Baymycard; Nisocor; Sular; Syscor; Zadipina;
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%.
Toxicity (Overdose): Not Available
Protein Binding: 99%
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.
Half Life: 7-12 hours
Dosage Forms of Zadipina: Tablet, coated Oral
Chemical IUPAC Name: O5-methyl O3-(2-methylpropyl) 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate
Chemical Formula: C20H24N2O6
Nisoldipine on Wikipedia: https://en.wikipedia.org/wiki/Nisoldipine
Organisms Affected: Humans and other mammals
