Sildenafil is not an ACE inhibitor. This common misconception arises because both medication classes can affect blood pressure, but they work through entirely different mechanisms and treat different conditions. Sildenafil belongs to a class called phosphodiesterase type 5 (PDE5) inhibitors and is prescribed for erectile dysfunction and pulmonary arterial hypertension. ACE inhibitors, such as ramipril and lisinopril, are cardiovascular medications that treat high blood pressure, heart failure, and kidney protection. Understanding these fundamental differences is essential for safe medication use and appropriate treatment selection.

What Is Sildenafil and How Does It Work?

Sildenafil is not an ACE inhibitor. It belongs to a completely different class of medications called phosphodiesterase type 5 (PDE5) inhibitors. Sildenafil is primarily prescribed for two distinct conditions: erectile dysfunction (ED) and pulmonary arterial hypertension (PAH). In the UK, it is available under various brand names including Viagra for ED and Revatio for PAH. Viagra Connect is also available from pharmacies without prescription following assessment by a pharmacist.

The mechanism of action of sildenafil centres on its ability to inhibit the PDE5 enzyme, which is found in various tissues but has particularly important functional roles in the blood vessels of the penis and lungs. When sexual stimulation occurs, the body naturally releases nitric oxide, which triggers the production of cyclic guanosine monophosphate (cGMP). This chemical messenger causes smooth muscle relaxation and increased blood flow. PDE5 normally breaks down cGMP, but sildenafil blocks this process, allowing cGMP levels to remain elevated for longer periods.

In erectile dysfunction, this mechanism enables improved blood flow to the penis, facilitating the achievement and maintenance of an erection sufficient for sexual activity. The medication typically begins working within 30 to 60 minutes of oral administration (though high-fat meals may delay absorption) and its effects can last for approximately four to five hours. The usual dose range is 25-100mg taken as needed. It is important to note that sildenafil requires sexual stimulation to be effective—it does not cause spontaneous erections.

For pulmonary arterial hypertension, sildenafil works by relaxing the blood vessels in the lungs, reducing the pressure in the pulmonary arteries and improving exercise capacity. The dosing regimen for PAH (typically 20mg three times daily) differs significantly from ED treatment, and patients should never interchange prescriptions intended for different conditions.

Important safety information: Sildenafil must never be taken with nitrate medications (such as glyceryl trinitrate for angina) or riociguat (a guanylate cyclase stimulator), as these combinations can cause severe, potentially life-threatening hypotension. Caution is needed when taking sildenafil with alpha-blockers (used for prostate conditions or high blood pressure), strong CYP3A4 inhibitors (like erythromycin or ketoconazole), or grapefruit juice. Erectile dysfunction may be an early warning sign of cardiovascular disease, so discussing this symptom with your GP is important, particularly if you have risk factors.

What Are ACE Inhibitors and Their Mechanism of Action?

Angiotensin-converting enzyme (ACE) inhibitors represent an entirely different class of cardiovascular medications with a distinct mechanism of action. Common examples available in the UK include ramipril, lisinopril, perindopril, and enalapril. These medications are prescribed for hypertension (high blood pressure), heart failure with reduced ejection fraction, cardiovascular protection following myocardial infarction, and to provide renoprotection in patients with diabetes and/or kidney disease with albuminuria.

ACE inhibitors work by blocking the angiotensin-converting enzyme, which plays a crucial role in the renin-angiotensin-aldosterone system (RAAS)—a hormonal cascade that regulates blood pressure and fluid balance. Normally, ACE converts angiotensin I into angiotensin II, a potent vasoconstrictor that narrows blood vessels and increases blood pressure. Angiotensin II also stimulates the release of aldosterone, which causes the kidneys to retain sodium and water, further elevating blood pressure.

By inhibiting ACE, these medications prevent the formation of angiotensin II, resulting in:

• Vasodilation (widening of blood vessels)

• Reduced blood pressure

• Decreased workload on the heart

• Reduced sodium and water retention

• Improved cardiac output in heart failure

• Protection of kidney function in certain conditions

According to NICE guidance, ACE inhibitors are considered first-line treatment for hypertension in people under 55 years of age and those not of Black African or African-Caribbean family origin (for whom calcium channel blockers are generally preferred first-line). They have been extensively studied and demonstrate significant benefits in reducing cardiovascular morbidity and mortality.

Common adverse effects include a persistent dry cough (affecting approximately 10-15% of patients), hypotension (particularly after the first dose), hyperkalaemia (elevated potassium levels), and rarely, angioedema (which is more common in Black patients). ACE inhibitors are absolutely contraindicated in pregnancy as they can cause foetal harm.

Patients starting ACE inhibitors require monitoring of renal function and electrolytes before starting treatment and within one to two weeks of initiation or dose adjustment. During illness with dehydration (vomiting, diarrhoea, fever), patients should seek medical advice as temporary suspension of treatment may be needed to prevent acute kidney injury.

Key Differences Between Sildenafil and ACE Inhibitors

Understanding the fundamental differences between sildenafil and ACE inhibitors is essential for patient safety and appropriate medication use. These two drug classes differ substantially in their pharmacology, indications, and clinical applications.

Pharmacological Classification and Mechanism: Sildenafil is a PDE5 inhibitor that works by preventing the breakdown of cGMP in smooth muscle cells, primarily affecting localised blood flow in specific vascular beds. ACE inhibitors, conversely, are cardiovascular agents that systemically block the RAAS, affecting blood pressure regulation throughout the entire body. The mechanisms are fundamentally different and non-overlapping.

Primary Indications:

• Sildenafil: Erectile dysfunction and pulmonary arterial hypertension

• ACE inhibitors: Hypertension (particularly in younger patients and non-Black populations), heart failure with reduced ejection fraction, post-myocardial infarction, diabetic nephropathy, and chronic kidney disease with albuminuria

Effect on Blood Pressure: Whilst both medication classes can lower blood pressure, they do so through entirely different pathways and to different degrees. ACE inhibitors are specifically designed as antihypertensive agents and produce sustained, predictable blood pressure reduction. Sildenafil may cause modest, transient blood pressure lowering (typically 8-10 mmHg systolic), but this is not its primary therapeutic effect and is generally clinically insignificant in healthy individuals. Importantly, sildenafil is not an antihypertensive medication and should never be used to treat high blood pressure.

Important Drug Interactions: A critical safety consideration is that sildenafil should never be taken with nitrate medications (such as glyceryl trinitrate for angina) or riociguat, as these combinations can cause severe, potentially life-threatening hypotension. Caution is needed when using sildenafil with alpha-blockers and strong CYP3A4 inhibitors. Sildenafil can generally be used safely alongside ACE inhibitors, though caution is advised in patients with already low blood pressure or those taking multiple antihypertensive medications.

Adverse Effect Profiles: Sildenafil commonly causes headache, facial flushing, dyspepsia, and nasal congestion. ACE inhibitors characteristically cause dry cough, dizziness, and require monitoring for hyperkalaemia and renal function changes. These side effect profiles reflect their different mechanisms and sites of action.

When to Speak to Your GP About Blood Pressure Medications

Knowing when to seek medical advice regarding blood pressure medications is crucial for maintaining cardiovascular health and ensuring safe medication use. Several situations warrant consultation with your GP or healthcare provider.

If you are considering sildenafil and have cardiovascular conditions: Patients with pre-existing heart disease, previous stroke, uncontrolled hypertension, or hypotension should discuss sildenafil use with their GP before obtaining a prescription. Whilst sildenafil is not an ACE inhibitor, it does have cardiovascular effects that require assessment in the context of your overall health status. Your GP will need to review your complete medication list, as certain combinations—particularly with nitrates or riociguat—are absolutely contraindicated. Caution is also needed if you take alpha-blockers or certain other medications.

If you experience side effects from current medications: The persistent dry cough associated with ACE inhibitors affects a significant proportion of patients and can substantially impact quality of life. If you develop this symptom, contact your GP—alternative medications such as angiotensin receptor blockers (ARBs) may be more suitable. Similarly, if sildenafil causes problematic side effects or proves ineffective, other treatment options exist.

When starting or stopping blood pressure medications: Never discontinue ACE inhibitors or other antihypertensive medications without medical supervision, as this can lead to worsening or loss of blood pressure control. If you believe your blood pressure medication is causing problems, arrange a medication review with your GP rather than stopping treatment independently.

Special situations requiring medical advice:

• If you are pregnant or planning pregnancy: ACE inhibitors are contraindicated in pregnancy and must be stopped immediately with medical supervision if pregnancy occurs

• During episodes of vomiting, diarrhoea or fever: Temporary suspension of ACE inhibitors may be needed to prevent kidney problems during dehydration

• Before surgery: Your anaesthetist needs to know about all your medications

Red flag symptoms requiring urgent attention:

• Severe dizziness or fainting (possible hypotension)

• Swelling of the face, lips, or tongue (potential angioedema—call 999)

• Chest pain or difficulty breathing

• Sudden vision or hearing loss (rare but serious sildenafil adverse effect)

• Erection lasting more than four hours (priapism—seek emergency care)

For medication reviews: NICE recommends regular review of all cardiovascular medications. If you take multiple medications for blood pressure or heart conditions, annual reviews ensure optimal management and allow adjustment based on current blood pressure readings, renal function, and any new symptoms.

If you experience any suspected side effects from your medication, you can report them directly to the MHRA through the Yellow Card scheme (yellowcard.mhra.gov.uk).

Frequently Asked Questions