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isosorbide dinitrate (Isordil, Sorbitrate, Isordil Tembids, Dinitrate SR, ISDN)

Tradenames: Isordil, Sorbitrate; Isordil Tembids, Dinitrate SR (sustained-release). Indications: 1) temporary relief of angina pectoris 2) long-term prophylaxis for angina pectoris 3) used in combination with hydralazine for management of CHF Contraindications: 1) increased intracranial pressure 2) constrictive pericarditis or tamponade Dosage: 1) SL for acute angina: 2.5-10 mg every 2-3 hours PRN 2) PO for prophylaxis of angina & for CHF a) 10-60 mg every 4-6 hours b) max dose 120 mg QD 3) sustained release: - 40-80 mg every 8-12 hours (at 0800 & 1400) 4) a daily nitrate free period of at least 12 hours is desirable to minimize tolerance Tabs: 5, 10, 20, 40 mg. Sublingual: 1 PRN. Tabs: 2.5, 5, 10 mg. Sustained-release: Tabs: 40 mg. Pharmacokinetics: 1) bioavailability varies between different products & different routes of administration (SL vs PO) 2) sublingual (SL) route may afford better bioavailability 3) onset of action a) SL: 5-20 minutes b) PO: 15-45 minutes 4) elimination 1/2 life varies from minutes to hours depending upon route of administration & single vs multiple doses Adverse effects: 1) common (> 10%) - headache, flushing, lightheadedness, dizziness, weakness, orthostatic hypotension 2) less common (1-10%) - drug rash, exfoliative dermatitis 3) uncommon (< 1%) - nausea/vomiting, methemoglobinemia (with overdose) 4) other - tachycardia - flushing - tolerance & dependence occur with long-term use Drug interactions: 1) antihypertensive agents in combination may result in additive hypotensive effects 2) alcohol in combination may result in increased hypotensive effects 3) sildenafil in combination is contraindicated a) bradycardia b) hypotension c) risk of sudden death 4) may antagonize anticoagulant effect of heparin Mechanism of action: 1) converted to nitric oxide (NO) by vascular endothelium (EDRF) 2) NO activates guanylate cyclase 3) increased cGMP decreases intracellular Ca+2 resulting in direct relaxation of vascular smooth muscle 4) venous system is affected more than the arterial system a) decreased preload b) some decrease in afterload

Interactions

drug interactions drug adverse effects of antihypertensive agents

Related

guanyl cyclase or guanylate cyclase nitric oxide (NO, endothelium derived relaxation factor {EDRF}) sildenafil (Viagra, Revatio, Caverta)

General

nitrate

Properties

MISC-INFO: elimination route LIVER pregnancy-category C safety in lactation ?

Database Correlations

PUBCHEM correlations

References

  1. The Pharmacological Basis of Therapeutics, 9th ed. Gilman et al, eds. Permagon Press/McGraw Hill, 1996
  2. Drug Information & Medication Formulary, Veterans Affairs, Central California Health Care System, 1st ed., Ravnan et al eds, 1998
  3. Kaiser Permanente Northern California Regional Drug Formulary, 1998

Component-of

hydralazine/isosorbide dinitrate (BiDiL)