isosorbide dinitrate (Isordil, Sorbitrate, Isordil Tembids, Dinitrate SR, ISDN)
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Introduction
Tradenames: Isordil, Sorbitrate; Isordil Tembids, Dinitrate SR (sustained-release).
Indications
- temporary relief of angina pectoris
- long-term prophylaxis for angina pectoris
- used in combination with hydralazine for management of CHF
Contraindications
- increased intracranial pressure
- constrictive pericarditis or tamponade
Dosage
- SL for acute angina: 2.5-10 mg every 2-3 hours PRN
- PO for prophylaxis of angina & for CHF
- 10-60 mg every 4-6 hours
- max dose 120 mg QD
- sustained release:
- 40-80 mg every 8-12 hours (at 0800 & 1400)
- 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
- bioavailability varies between different products & different routes of administration (SL vs PO)
- sublingual (SL) route may afford better bioavailability
- onset of action
- elimination 1/2 life varies from minutes to hours depending upon route of administration & single vs multiple doses
elimination via liver
Adverse effects
- common (> 10%)
- less common (1-10%)
- uncommon (< 1%)
- nausea/vomiting, methemoglobinemia (with overdose)
- other
- tachycardia
- flushing
- tolerance & dependence occur with long-term use
Drug interactions
- antihypertensive agents in combination may result in additive hypotensive effects
- alcohol in combination may result in increased hypotensive effects
- sildenafil in combination is contraindicated
- bradycardia
- hypotension
- risk of sudden death
- may antagonize anticoagulant effect of heparin
- drug interaction(s) of nitrates with phosphodiesterase-5-inhibitors
- drug interaction(s) of phosphodiesterase-5-inhibitor with nitrates
- drug interaction(s) of NSAIDs & antihypertensives
Mechanism of action
- converted to nitric oxide (NO) by vascular endothelium (EDRF)
- NO activates guanylate cyclase
- increased cGMP decreases intracellular Ca+2 resulting in direct relaxation of vascular smooth muscle
- venous system is affected more than the arterial system
More general terms
Additional terms
- guanyl cyclase or guanylate cyclase
- nitric oxide (NO, endothelium derived relaxation factor {EDRF})
- sildenafil (Viagra, Revatio, Caverta)
Component of
References
- ↑ The Pharmacological Basis of Therapeutics, 9th ed. Gilman et al, eds. Permagon Press/McGraw Hill, 1996
- ↑ Drug Information & Medication Formulary, Veterans Affairs, Central California Health Care System, 1st ed., Ravnan et al eds, 1998
- ↑ Kaiser Permanente Northern California Regional Drug Formulary, 1998