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CARDIOVASCULAR SYSTEM › CARDIAC THERAPY › VASODILATORS USED IN CARDIAC DISEASES › Organic nitrates
organic nitrates in combination
C01DA20
Forms & Strengths
- Combination formulations containing organic nitrates (e.g., isosorbide dinitrate, nitroglycerin) with other cardiovascular agents
- Available as oral tablets, sustained-release capsules, and transdermal patches depending on the specific combination product
Adult Dosing
- Dosing is highly variable depending on the specific combination product and indication
- Typically initiated at the lowest available strength to minimize adverse effects such as headache and hypotension
- Must include a nitrate-free interval (typically 10-12 hours daily) to prevent the development of pharmacological tolerance
Pediatric Dosing
- Safety and efficacy in pediatric patients have not been established
- Use in children is generally not recommended
Indications
- Prophylaxis and long-term management of chronic stable angina pectoris
- Management of heart failure in specific combination therapies (e.g., isosorbide dinitrate with hydralazine)
Mechanism of Action
- Organic nitrates act as donors of nitric oxide (NO)
- Nitric oxide stimulates soluble guanylyl cyclase, increasing intracellular cyclic GMP
- Leads to dephosphorylation of myosin light chains and relaxation of vascular smooth muscle
- Produces preferential dilation of capacitance vessels (veins), reducing preload and myocardial oxygen demand
Contraindications
- Hypersensitivity to organic nitrates or any component of the formulation
- Concurrent use of phosphodiesterase-5 (PDE-5) inhibitors (e.g., sildenafil, tadalafil, vardenafil)
- Concurrent use of soluble guanylyl cyclase stimulators (e.g., riociguat)
- Severe anemia, increased intracranial pressure, or uncorrected hypovolemia
- Angle-closure glaucoma (for specific oral/systemic formulations)
Adverse Reactions
- Throbbing headache (very common, typically diminishes with continued therapy)
- Orthostatic hypotension, dizziness, and lightheadedness
- Reflex tachycardia and flushing
- Nausea and vomiting
- Contact dermatitis (associated with transdermal delivery systems)
Drug Interactions
- Phosphodiesterase-5 (PDE-5) inhibitors: severe, potentially fatal profound hypotension
- Soluble guanylyl cyclase stimulators (riociguat): profound hypotension and syncope
- Antihypertensive agents, beta-blockers, and calcium channel blockers: additive hypotensive effects
- Alcohol: enhanced hypotensive response and CNS depression
Curated Content: Needs Vetting Before Put to Clinical Use