Phosphodiesterase-5 (PDE-5) inhibitors are an important drug class used primarily in the treatment of erectile dysfunction (ED) and pulmonary arterial hypertension (PAH). Drugs such as sildenafil, tadalafil, and vardenafil are frequently tested in pharmacology because they clearly demonstrate:
- Nitric oxide (NO)–cGMP signaling
- Smooth muscle relaxation
- Targeted vasodilation
For MBBS, nursing, pharmacy, and allied health students, PDE-5 inhibitors are high-yield drugs that link physiology, pharmacology, and clinical medicine in a very logical way.
What Are PDE-5 Inhibitors?
PDE-5 inhibitors are drugs that:
- Inhibit the enzyme phosphodiesterase-5
- Increase levels of cyclic GMP (cGMP)
- Cause smooth muscle relaxation and vasodilation
Key Concept (Must Remember)
PDE-5 inhibitors do not cause erection directly.
They enhance the natural erectile response to sexual stimulation.
Common PDE-5 Inhibitors
This article focuses on three commonly used and tested drugs:
| Drug | Common Brand Names |
|---|---|
| Sildenafil | Viagra, Revatio |
| Tadalafil | Cialis |
| Vardenafil | Levitra |
Pharmacological Classification
Drug Class
Phosphodiesterase-5 inhibitorsTherapeutic Category
- Erectile dysfunction drugs
- Pulmonary vasodilators
Physiology Behind Erection (Concept Builder)
Understanding this makes the mechanism effortless.
1. Sexual stimulation → release of nitric oxide (NO)Role of PDE-5
- PDE-5 breaks down cGMP
- Limits duration of erection
👉 PDE-5 inhibitors block cGMP breakdown, prolonging erection.
Mechanism of Action (Very High-Yield)
How PDE-5 Inhibitors Work
Sildenafil, tadalafil, and vardenafil:
- Inhibit PDE-5 enzyme
- Prevent breakdown of cGMP
- Increase and prolong smooth muscle relaxation
Net Effects
- Vasodilation in penile tissue
- Improved erectile response
- Reduced pulmonary vascular resistance (in PAH)
Exam Pearl:
Sexual stimulation is required for PDE-5 inhibitors to work.
Individual Drug Profiles (Exam-Focused)
Sildenafil
Drug Class
PDE-5 inhibitorKey Features
- First drug in this class
- Shorter duration of action
Indications
- Erectile dysfunction
- Pulmonary arterial hypertension (lower dose)
Adverse Effects
- Headache
- Flushing
- Nasal congestion
- Blue-tinged vision (PDE-6 inhibition)
Clinical Pearl
Sildenafil is commonly associated with visual disturbances.
Tadalafil
Drug Class
PDE-5 inhibitorKey Features
- Longest duration of action (~36 hours)
- Once-daily low-dose option available
Indications
- Erectile dysfunction
- Benign prostatic hyperplasia (BPH)
- Pulmonary arterial hypertension
Adverse Effects
- Headache
- Flushing
- Back pain, myalgia (PDE-11 inhibition)
Clinical Pearl
Tadalafil is called the “weekend pill” due to its long duration.
Vardenafil
Drug Class
PDE-5 inhibitorKey Features
- Potency similar to sildenafil
- Slightly longer duration than sildenafil
Indications
Erectile dysfunctionAdverse Effects
- Headache
- Flushing
- QT prolongation (rare)
Clinical Pearl
Avoid vardenafil in patients with long QT syndrome.
Comparison Table (Very High-Yield)
| Feature | Sildenafil | Tadalafil | Vardenafil |
|---|---|---|---|
| Onset | Fast | Moderate | Fast |
| Duration | 4–6 h | Up to 36 h | 5–8 h |
| Visual effects | Yes | No | Rare |
| Back pain | No | Yes | No |
| BPH use | No | Yes | No |
Clinical Uses of PDE-5 Inhibitors
Primary Indications
- Erectile dysfunction
- Pulmonary arterial hypertension
Additional Uses
Benign prostatic hyperplasia (tadalafil)Adverse Effects (Important for Exams)
Common Side Effects
- Headache
- Flushing
- Dyspepsia
- Nasal congestion
Cardiovascular
Hypotension (especially with nitrates)Special Adverse Effects
- Sildenafil → blue vision
- Tadalafil → back pain
- Vardenafil → QT prolongation
Contraindications (Very Important)
Absolute Contraindication
❌ Nitrates (e.g., nitroglycerin)
Combination can cause severe, life-threatening hypotension.
Use with Caution
- Severe cardiac disease
- Hypotension
- Recent stroke or myocardial infarction
- Retinitis pigmentosa
Drug Interactions (Exam-Friendly)
- Nitrates → severe hypotension
- Alpha-blockers → hypotension
- CYP3A4 inhibitors → ↑ drug levels
Nursing & Patient Education
Key Counseling Points
- Take drug before sexual activity
- Sexual stimulation is required
- Do not use with nitrates
- Seek medical help for erection >4 hours (priapism)
Clinical & Exam Pearls (Must Remember)
- PDE-5 inhibit.the longest duration
Summary Table: PDE-5 Inhibitors at a Glance
| Parameter | Key Point |
|---|---|
| Drug class | PDE-5 inhibitors |
| Main action | ↑ cGMP |
| Main use | Erectile dysfunction |
| Special risk | Hypotension with nitrates |
| Longest acting | Tadalafil |
| Exam relevance | Very high |
FAQs
1. Do PDE-5 inhibitors cause erection without stimulation?
No. Sexual stimulation is required.
2. Which PDE-5 inhibitor lasts the longest?
Tadalafil.
3. Why are nitrates contraindicated?
Both drugs increase cGMP, causing severe hypotension.
4. Which drug causes blue vision?
Sildenafil.
5. Can PDE-5 inhibitors be used in heart patients?
Only with caution and never with nitrates.
6. Are PDE-5 inhibitors aphrodisiacs?
No. They improve erection, not desire.
7. Why is tadalafil useful in BPH?
It relaxes smooth muscle in the prostate and bladder neck.
8. What is the most common side effect?
Headache and flushing.
9. Which PDE-5 inhibitor affects QT interval?
Vardenafil.
10. What is the most tested exam concept?
PDE-5 inhibition → ↑ cGMP → smooth muscle relaxation.
