Sildenafil
Sildenafil is a potent **phosphodiesterase type 5 (PDE5) inhibitor**. While primarily recognized in human medicine for the treatment of erectile dysfunction, in veterinary pharmacology, it is a cornerstone therapy for **pulmonary hypertension (PH)**. * **Clinical Pearl**: It is particularly effective for dogs and cats suffering from PH secondary to chronic mitral valve disease, heartworm disease, or primary pulmonary diseases (such as pulmonary fibrosis). * By selectively dilating the pulmonary arterial bed, sildenafil significantly reduces right ventricular afterload, thereby improving clinical signs like syncope (fainting), exercise intolerance, and right-sided congestive heart failure. * It is highly specific to the pulmonary vasculature, meaning it typically does not cause severe systemic hypotension unless combined with other vasodilators.
Mechanism: Sildenafil exerts its effects via the **nitric oxide (NO) pathway** in smooth muscle cells: * Endothelial cells release **Nitric Oxide (NO)** โ activates the enzyme **guanylate cyclase** โ converts GTP to **cyclic guanosine monophosphate (cGMP)**. * **cGMP** acts as a secondary messenger causing smooth muscle relaxation and vasodilation. * **PDE5** is the enzyme responsible for degrading cGMP, and it is found in high concentrations in the pulmonary vasculature and corpus cavernosum. * **Mechanism**: Sildenafil competitively inhibits **PDE5** โ prevents cGMP breakdown โ intracellular cGMP accumulates โ resulting in prolonged and enhanced **NO-mediated pulmonary vasodilation**.
Dosing by species
- Moderate to severe PH secondary to either left heart disease or primary lung disease ยท 1 mg/kg ยท PO ยท q8h
- Pulmonary arterial hypertension ยท 1.6 mg/kg ยท PO ยท q12h ยท Reported dose tolerated and clinically efficacious.
- Pulmonary hypertension ยท 1.9 mg/kg (range from 0.5-2.7 mg/kg) ยท PO ยท q8-24h ยท Median dose from a retrospective study. Dogs may have been also treated with oxygen, ACE inhibitors, furosemide, amlodipine, diltiazem, theophylline, phenobarbital and/or antibiotics.
- Pulmonary hypertension documented by Doppler, chronic pulmonary disease, right-sided heart failure (HW disease; congenital) ยท 0.5-1 mg/kg (higher dose of 2 -3 mg/kg three times a day may be tolerated and needed) ยท PO ยท two times daily
- Moderate to severe PH secondary to either left heart disease or primary lung disease ยท 1 mg/kg ยท PO ยท q8h
- Pulmonary hypertension ยท 1-2 mg/kg ยท PO ยท three times daily
- Pulmonary arterial hypertension ยท 0.5-2.7 mg/kg (suggested median dose from clinical studies is 3 mg/kg/day) ยท PO ยท q8-24h ยท Improves quality of life despite lack of significant echocardiographic reduction in pressures.
Doses are a clinical reference for licensed veterinary professionals. Always confirm against the current label and the individual patient.
Routes of administration
Contraindications
- Concurrent use with organic nitrates
- Known hypersensitivity to sildenafil
- Pulmonary veno-occlusive disease (PVOD)
- Systemic hypotension
- Significant hepatic impairment
- Significant renal impairment
- Bleeding disorders
- Concurrent use of nitrates
Adverse effects
- Cutaneous flushing of the inguinal region
- Gastrointestinal effects (possible)
- Headache, visual disturbances, dyspepsia, nasal congestion, myalgia, priapism, dizziness, and back pain (reported in humans)
- Vomiting
- Dizziness / weakness
- Raised intraocular pressure
- Systemic hypotension (especially if combined with other vasodilators)
Drug interactions
- Alpha-adrenergic blockers (e.g., phentolamine, phenothiazines, phenoxybenzamine) ยท May increase hypotensive effects
- Amlodipine ยท Potential to increase hypotensive effects
- Antihypertensive, hypotensive drugs ยท Potentially could increase hypotensive effects
- Azole antifungals (ketoconazole, itraconazole) ยท May reduce sildenafil metabolism and increase AUC
- Cimetidine ยท May reduce sildenafil metabolism and increase AUC ยท moderate
- Erythromycin, Clarithromycin ยท May reduce sildenafil metabolism and increase AUC
- Heparin ยท May increase bleeding risks
- Nitrates (e.g., NTG, Isosorbide) ยท Significant potentiation of vasodilatory effects; life-threatening hypotension possible
- Nitroprusside sodium ยท Significant potentiation of vasodilatory effects; life-threatening hypotension possible
- Phenobarbital ยท May decrease sildenafil concentrations ยท moderate
- Rifampin ยท May decrease sildenafil concentrations
- Erythromycin ยท Increases plasma sildenafil concentration ยท moderate
- Itraconazole ยท Increases plasma sildenafil concentration ยท moderate
Monitoring
- Clinical efficacy (improved syncope, cough, respiratory effort)
- Pulmonary artery pressure
- Systemic blood pressure
- Adverse effects
- Clinical signs of pulmonary hypertension (exercise tolerance, syncope, respiratory rate/effort)
- Echocardiography (to monitor right heart function and pulmonary pressures)
- Intraocular pressure (if pre-existing ocular disease)
Overdose
Little information is available in veterinary species. In humans, massive overdose (2000 mg) resulted in tachycardia, nonspecific ST-T changes on ECG, headache, dizziness, and flushing. It is expected that overdoses in animals would mirror the drug's adverse effect profile (e.g., profound hypotension, tachycardia, cutaneous flushing). **Treat supportively.**
VetSheet drug reference is intended for licensed veterinary professionals as a clinical decision-support aid, not a substitute for professional judgement or the manufacturerโs current label.