How does sildenafil (phosphodiesterase type 5 inhibitor) affect blood pressure?

How Sildenafil Affects Blood Pressure

Sildenafil causes mild, transient decreases in blood pressure through systemic vasodilation, typically reducing systolic/diastolic pressure by approximately 8-10/5-9 mmHg, with effects peaking 1-2 hours after dosing. 1

Mechanism of Blood Pressure Reduction

• Sildenafil inhibits phosphodiesterase type 5 (PDE-5), which increases cyclic GMP in vascular smooth muscle, causing vasodilation in both pulmonary and systemic circulation 1
• The vasodilatory effect results in mild peripheral arterial-venous dilatation, leading to modest preload and afterload reductions 1, 2
• Single oral doses of 100 mg in healthy volunteers produced mean maximum decreases of 8/5 mmHg in supine blood pressure 1
• After chronic dosing of 80 mg three times daily to healthy volunteers, the largest mean decrease was 9.0/8.4 mmHg 1

Blood Pressure Effects in Different Patient Populations

In hypertensive patients: After chronic dosing of 80 mg three times daily, mean reductions were 9.4/9.1 mmHg 1

In pulmonary arterial hypertension (PAH) patients: Lesser reductions of approximately 2/2 mmHg were observed with the same dosing regimen 1

The blood pressure reduction is not dose-dependent within the therapeutic range (25-100 mg), as similar effects were noted across all doses 1

Critical Safety Considerations

Absolute Contraindication with Nitrates

• Never combine sildenafil with nitrate medications due to profound, potentially life-threatening hypotension from synergistic vasodilation 3
• The combination causes synergistic increases in cGMP levels at different points along the NO-cGMP pathway, resulting in excessive blood pressure drops 4
• Avoid nitrates for at least 24 hours after sildenafil use 3

Other Blood Pressure-Related Contraindications

• Avoid sildenafil in patients with resting hypotension (BP <90/50 mmHg) 3, 1
• Avoid in patients with severe left ventricular outflow obstruction 3, 1
• Avoid in patients with autonomic dysfunction 3, 1
• Control uncontrolled hypertension (BP ≥180/110 mmHg) before prescribing sildenafil 3

Safety with Antihypertensive Medications

Sildenafil can be safely prescribed with most antihypertensive agents without significant adverse reactions 3

• Diuretics can be used in combination without significant safety concerns 3
• Angiotensin II receptor blockers (ARBs) can be combined without increased adverse events 3
• Beta blockers, alpha blockers, ACE inhibitors, and calcium antagonists did not show increased adverse events in retrospective analyses 4
• Monitor blood pressure when co-administering blood pressure lowering drugs with sildenafil 1

Common Vasodilation-Related Side Effects

• Headache occurs in 16% of patients, related to vasodilation 3, 4
• Flushing occurs in 10% of patients 3, 4
• Dizziness occurs in 2% of patients 4
• The incidence of hypotension, orthostatic hypotension, and syncope was <2% and similar to placebo 4

Clinical Implications

• The blood pressure effects are transient, with maximum effects at 1-2 hours post-dose and no difference from placebo at 8 hours 1
• Carefully consider underlying conditions that could be adversely affected by vasodilatory effects, including patients on antihypertensive therapy, fluid depletion, or with cardiovascular instability 1
• In clinical trials of patients with ischemic heart disease, sildenafil did not increase serious cardiovascular events, myocardial infarction, or death compared to placebo 2, 5