Nisoldipine

3.1

3.59

Breast Feeding; Lactation; Antihypertensive Agents; Calcium Channel Blockers; Vasodilator Agents;

FDA approved drugs -> Active ingredient

FDA approved drugs -> Active ingredient

195.5 Ų [M+Na]+ [CCS Type: DT; Buffer gas: N2; Ionization: ESI+; Dataset: TOXCAST; Source Identifier: DTXSID0023371]

190.3 Ų [M+Na]+ [CCS Type: TW; Method: calibrated with polyalanine and drug standards]

187.2 Ų [M+H]+ [CCS Type: TW; Method: calibrated with polyalanine and drug standards]

Warning

H302 (100%): Harmful if swallowed [Warning Acute toxicity, oral]

P203, P264, P270, P273, P280, P301+P317, P302+P352, P317, P318, P321, P330, P362+P364, P391, P405, and P501 (click each P-code to see the statement)

Aggregated GHS information provided per 69 reports by companies from 5 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Though nisoldipine is well-tolerated among patients, the drug does have some side effects mainly associated with its vasodilating property. Common adverse effects associated with nisoldipine include flushing, vasodilation (4%), hypotension, syncope, peripheral edema (7% to 29%,dose-related), headache (22%), dizziness (3% to 10%), and nausea (2%).

Toxicity due to nisoldipine is diagnosed based on clinical status and history. As described above, hypotension with reflex tachycardia can occur when patients take excessive doses of dihydropyridine calcium channel blockers such as nisoldipine. In some severe cases of nisoldipine toxicity, the clinician will note hypotension with bradycardia. Secondary findings of confusion, heart failure, and abnormal ECG changes such as PR prolongation can indicate toxicity. Additionally, hyperglycemia in patients without diabetes can suggest calcium channel blockers poisoning.

Drug Induced Liver Injury Rank (DILIrank 2.0)

Nisoldipine

Ambiguous-DILI-concern

3

Adverse reactions

DOI:10.1016/j.drudis.2016.02.015

C - Cardiovascular system

QC - Cardiovascular system

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.

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.

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.

Nisoldipine has known human metabolites that include 5-O-(1-hydroxy-2-methylpropyl) 3-O-methyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, 2,6-Dimethyl-5-(2-methylpropoxycarbonyl)-4-(2-nitrophenyl)-1,4-dihydropyridine-3-carboxylic acid, and Dehydro Nisoldipine.

4I8HAB65SZ

NISOLDIPINE

Established Pharmacologic Class [EPC] - Dihydropyridine Calcium Channel Blocker

Chemical Structure [CS] - Dihydropyridines

Mechanisms of Action [MoA] - Calcium Channel Antagonists

Physiologic Effects [PE] - Decreased Blood Pressure

Drugs used in the treatment of acute or chronic vascular HYPERTENSION regardless of pharmacological mechanism. Among the antihypertensive agents are DIURETICS; (especially DIURETICS, THIAZIDE); ADRENERGIC BETA-ANTAGONISTS; ADRENERGIC ALPHA-ANTAGONISTS; ANGIOTENSIN-CONVERTING ENZYME INHIBITORS; CALCIUM CHANNEL BLOCKERS; GANGLIONIC BLOCKERS; and VASODILATOR AGENTS.

A class of drugs that act by selective inhibition of calcium influx through cellular membranes.

Drugs used to cause dilation of the blood vessels.

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%.

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