Phosphodiesterase Type 5 (PDE5) inhibitors are medications widely used to treat erectile dysfunction (ED) by enhancing blood flow to the penis during sexual stimulation. The most commonly recognized drug in this class is Sildenafil, marketed as Viagra. These medications are highly effective, but they also carry significant cardiovascular precautions and drug interaction risks that healthcare learners must understand.
What Are PDE5 Inhibitors?
PDE5 inhibitors are a class of drugs that improve erectile function by enhancing the natural nitric oxide (NO) pathway. This leads to increased blood flow to erectile tissue.
Common medications include:
- Sildenafil (Viagra)
- Tadalafil (Cialis)
- Vardenafil (Levitra)
- Avanafil (Stendra)
These medications are taken orally (PO), usually before anticipated sexual activity.
Classification
Pharmacologic Class (P): Phosphodiesterase Type 5 Inhibitors
Therapeutic Class (T): Erectile Dysfunction Drugs
Uses of Sildenafil (Viagra)
Erectile Dysfunction (ED)
Sildenafil is used to improve the ability to achieve and maintain an erection during sexual stimulation.
Additional Uses
Pulmonary Arterial Hypertension (PAH) (at different dosing under brand name Revatio)However, the primary and most common use is for ED.
Mechanism of Action (MOA)
Sildenafil works by enhancing the effects of nitric oxide (NO), a natural chemical released during sexual stimulation.
How it Works:
- Sexual arousal releases nitric oxide (NO).
- NO activates cyclic guanosine monophosphate (cGMP) → relaxes smooth muscle.
- Smooth muscle relaxation increases blood flow to the penis, creating an erection.
- Normally, PDE5 breaks down cGMP.
- Sildenafil inhibits PDE5, allowing cGMP to stay active longer → prolonged erection.
Important note: Sexual stimulation is required for sildenafil to work. It does not cause automatic erections.
Adverse Effects of PDE5 Inhibitors
A helpful mnemonic from the visual is HARD (since the purpose is to sustain an erection):
H – Hearing Loss
Rare but serious sudden sensorineural hearing loss.
A – Abnormal Vision Changes
Includes:
- Blue/green color distortion
- Light sensitivity
- Vision blurring
This happens because PDE5 is related to PDE6 in retinal cells.
R – Risk of Stroke
Especially in patients with underlying cardiovascular disease.
D – Diarrhea and Nausea
Common gastrointestinal side effects.
Additional Adverse Effects
- Headache (most common)
- Flushing
- Nasal congestion
- Dizziness
- Priapism (erection lasting >4 hours — medical emergency)
- Hypotension (especially with nitrates)
These effects occur due to increased vasodilation throughout the body.
Drug Interactions
1. Nitroglycerin (and all nitrates) – Absolute Contraindication
Combining nitrates with sildenafil causes severe, life-threatening hypotension due to massive vasodilation.
Examples of nitrates:
- Nitroglycerin
- Isosorbide dinitrate
- Isosorbide mononitrate
- Recreational “poppers” (amyl nitrate)
This is the most important safety point.
2. Grapefruit Juice
Increases sildenafil levels by inhibiting CYP3A4 metabolism.
3. Alpha-blockers (e.g., tamsulosin)
May increase the risk of symptomatic hypotension.
4. Antihypertensive drugs
Additive blood pressure–lowering effects.
Contraindications
Sildenafil should not be used in:
1. Nitroglycerin or Nitrate Use
Absolute—life-threatening hypotension can occur.
2. History of Stroke
Increased risk of cerebrovascular complications.
3. Peptic Ulcer Disease
Due to increased bleeding risk.
4. Severe Hepatic or Renal Impairment
Slowed drug metabolism can worsen side effects.
5. Severe Low Blood Pressure or Uncontrolled Hypertension
Unsafe cardiovascular effects.
6. Retinitis Pigmentosa
Risk of visual damage due to PDE deficiencies.
Clinical Pearls for Students
- Sildenafil requires sexual stimulation to work.
- Take 30–60 minutes before sexual activity; effects last 3–5 hours.
- Avoid taking with a high-fat meal — absorption decreases.
- Priapism (>4 hours) is a medical emergency.
- Tadalafil (Cialis) has the longest duration (~36 hours).
These points frequently appear in NCLEX and pharmacology examinations.
Patient Education
Teach patients to:
NEVER tak ication only when needed (not daily unless prescribed for PAH).
Education increases safety and effectiveness.
PDE5 inhibitors like Sildenafil (Viagra) are highly effective medications for erectile dysfunction and pulmonary hypertension. Their mechanism enhances the nitric oxide pathway, improving penile blood flow during sexual stimulation. However, they come with significant cardiovascular risks, especially when combined with nitrates. Understanding their uses, adverse effects, contraindications, and interactions is essential for safe clinical practice.
For students, PDE5 inhibitors are a high-yield pharmacology topic due to their widespread use and well-defined safety concerns.
FAQs on PDE5 Inhibitors (Sildenafil)
1. Does Viagra cause automatic erections?
No. Sexual stimulation is required.
2. Why is sildenafil dangerous with nitroglycerin?
The combination causes life-threatening hypotension.
3. How long does Viagra last?
Approximately 3–5 hours.
4. Can women take sildenafil?
Not routinely recommended; research uses exist but benefits are limited.
5. What is priapism?
A prolonged erection lasting over 4 hours — a medical emergency.
6. Can sildenafil affect vision?
Yes. PDE6 involvement can cause color vision changes.
7. Does sildenafil work for everyone?
No; effectiveness depends on underlying health, timing, and stimulation.
