isosorbide dinitrate
Brand: Isordil
Prototype: nitroglycerin
Drug Class: nitrate
Drug Family: antianginal
Subclass: organic nitrate (NO donor)
Organ Systems: cardiovascular
Mechanism of Action
Organic nitrate converted to active mononitrate metabolite; shorter acting than ISMN; combined with hydralazine for HFrEF in Black patients (A-HeFT).
guanylyl cyclase via NO
Indications
- chronic angina prophylaxis
- heart failure (with hydralazine)
Contraindications
- PDE-5 inhibitors
- severe hypotension
Adverse Effects
Common
- headache
- hypotension
- tolerance
Serious
- severe hypotension
Pharmacokinetics (ADME)
| Absorption | 22-58% oral (first-pass) |
| Distribution | moderate |
| Metabolism | hepatic to ISMN |
| Excretion | renal |
| Half-life | 1 hour |
| Onset | 1.5 hours |
| Peak | 2 hours |
| Duration | 4-6 hours |
| Protein Binding | 28% |
| Vd | 2.5 L/kg |
Drug Interactions
| Drug / Agent | Mechanism | Severity |
|---|---|---|
| PDE-5 inhibitors | profound hypotension | major |
Nursing Considerations
- A-HeFT used ISDN 40 mg TID + hydralazine 75 mg TID
- Three-times daily dosing with 10-12h nitrate-free interval
- Fixed dose combination BiDil approved for Black patients with HFrEF
Clinical Pearls
- A-HeFT trial: BiDil (ISDN + hydralazine fixed dose) — 43% relative risk reduction in all-cause mortality in Black HFrEF patients
Safety Profile
Pregnancy use-with-caution
Lactation avoid
Renal Adjustment Not required
Hepatic Adjustment Not required
TDM Not required
Concordance Terms
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