Isosorbide
Isosorbide dinitrate and isosorbide mononitrate are organic nitrate vasodilators with potential adjunctive use in veterinary heart failure. Their principal intended effect is reduction of venous filling pressures and cardiac preload. They are pharmacologically distinct from non-nitrated isosorbide used as an osmotic agent, and veterinary clinical experience with nitrate formulations is limited.
Group
Nitrate vasodilator
Mechanism of Action
Organic nitrate bioactivation increases nitric-oxide-related signaling in vascular smooth muscle. Activation of soluble guanylyl cyclase raises cyclic GMP and promotes smooth-muscle relaxation, with a prominent effect on venous capacitance vessels. Increased venous capacity reduces return of blood to the heart and lowers filling pressures. At greater exposure, arterial dilation can also reduce systemic resistance.
Dose Rates
Dogs
| Use / stage | Dose | Route | Schedule | Instructions |
|---|---|---|---|---|
| Preload reduction | 2.5–5 mg/animal | PO | Every 12 h | Dinitrate formulation; fixed-dose alternative. |
| Preload reduction | 0.22–1.1 mg/kg | PO | Every 12 h | Dinitrate formulation; weight-based alternative. |
| Preload reduction with mononitrate | Reference only | PO | 5 mg/dog twice daily, with the two doses 7 hours apart and a longer overnight gap; do not encode as a repeating 7-hour interval. | |
| Refractory heart-failure adjunct | 0.5–2 mg/kg | PO | Every 12 h | Dinitrate; efficacy is incompletely established. |
| Refractory heart-failure mononitrate alternative | Reference only | PO | Mononitrate 0.25-2 mg/kg twice daily; formulation is distinct from dinitrate and must not be converted through dinitrate tablets. |
Cats
| Use / stage | Dose | Route | Schedule | Instructions |
|---|---|---|---|---|
| Preload reduction | 2.5–5 mg/animal | PO | Every 12 h | Dinitrate formulation; fixed-dose alternative. |
| Preload reduction | 0.22–1.1 mg/kg | PO | Every 12 h | Dinitrate formulation; weight-based alternative. |
| Thyroid-storm heart-failure adjunct | 0.5–2 mg/kg | PO | Every 8–12 h | Dinitrate; begin at the low end and titrate. |
| Refractory heart-failure adjunct | 0.5–2 mg/kg | PO | Every 12 h | Dinitrate; efficacy is incompletely established. |
| Refractory heart-failure mononitrate alternative | Reference only | PO | Mononitrate 0.25-2 mg/kg twice daily; formulation is distinct from dinitrate and must not be converted through dinitrate tablets. |
Indications
- Empirical adjunctive preload reduction in selected dogs or cats with congestive heart failure and elevated filling pressures; clinical outcome evidence for isosorbide nitrates is limited.
Contraindications
- Hypovolaemia
- Use cautiously with poor cardiac reserve.
- Shock; nitrate therapy must not be the sole treatment of congestive heart failure.
Interactions
- Other vasodilators may intensify hypotension.
Adverse effects
- Hypotension and tolerance during repeated dosing
Toxicity
Excess vasodilation requires withdrawal and haemodynamic support.
Preparations
| Preparation | Form | Strength | Route |
|---|---|---|---|
| Isosorbide dinitrate 5 mg tablet | Tablet | 5 mg / tablet | PO |
| Isosorbide dinitrate 10 mg tablet | Tablet | 10 mg / tablet | PO |
| Isosorbide dinitrate 20 mg tablet | Tablet | 20 mg / tablet | PO |
| Isosorbide dinitrate 40 mg tablet | Tablet | 40 mg / tablet | PO |
| Isosorbide dinitrate 40 mg capsule | Capsule | 40 mg / capsule | PO |
| Isosorbide mononitrate 10 mg tablet | Tablet | 10 mg / tablet | PO |
| Isosorbide mononitrate 20 mg tablet | Tablet | 20 mg / tablet | PO |
| Isosorbide dinitrate 30 mg tablet | Tablet | 30 mg / tablet | PO |
Monitoring and Administration
Monitor blood pressure and clinical perfusion.
Dinitrate and mononitrate require different schedules; they must not be interchanged by mass alone.
Store protected from light at room temperature.