35.5 Phosphodiesterase 5 Inhibitors

Mechanism of Action and Indications

PDE5 inhibitors treat benign prostatic hyperplasia (BPH), erectile dysfunction (ED), and pulmonary arterial hypertension. They work by relaxing smooth muscle in the lower urinary tract and vasculature, which makes them useful across all three conditions.

How PDE5 Inhibitors Work

Normally, an enzyme called phosphodiesterase type 5 (PDE5) breaks down a signaling molecule called cGMP inside smooth muscle cells. cGMP is what tells smooth muscle to relax.

PDE5 inhibitors block that enzyme, so cGMP accumulates. More cGMP means more smooth muscle relaxation. In the context of BPH, this relaxation occurs in the prostate, urethra, and bladder neck, which improves urine flow and reduces symptoms like:

• Difficulty starting urination
• Frequent urination
• Weak urine stream

Tadalafil (Cialis) is the only PDE5 inhibitor currently FDA-approved for BPH. Sildenafil (Viagra) and vardenafil (Levitra) are approved for ED but not BPH.

Indications, Side Effects, and Contraindications

Common side effects include:

• Headache and flushing (from vasodilation)
• Dyspepsia (indigestion)
• Nasal congestion
• Back pain (more common with tadalafil)
• Visual disturbances: blue-tinged vision or increased light sensitivity, caused by mild cross-reactivity with PDE6 in the retina

Contraindications are critical to know:

• Concurrent nitrate use (e.g., nitroglycerin, isosorbide): Both drugs cause vasodilation, and combining them can cause severe, life-threatening hypotension
• Hypotension (BP < 90/50 mmHg)
• Recent MI or stroke within the last 6 months
• Severe hepatic impairment
• Known hereditary degenerative retinal disorders (e.g., retinitis pigmentosa)

Nursing Considerations and Patient Education

Nursing Considerations

1. Assess for contraindications first. Obtain a complete medication history, including OTC drugs, herbal supplements, and especially any nitrate-containing medications. Patients sometimes don't think to mention recreational nitrate use (poppers), which carries the same hypotension risk.
2. Monitor blood pressure before and after administration. Withhold the medication if BP is below 90/50 mmHg.
3. Know the food interactions. Sildenafil and vardenafil absorb best on an empty stomach; high-fat meals can delay their onset. Tadalafil can be taken with or without food.
4. Educate on side effects and when to seek emergency care (see below).
5. Store medications at room temperature, away from moisture and heat.

Patient Education

Onset and duration differ by drug:

Tadalafil's much longer duration is why it's sometimes called "the weekend pill" and why it works well as a daily low-dose option for BPH.

Key teaching points:

• Avoid grapefruit and grapefruit juice. Grapefruit inhibits CYP3A4 metabolism of these drugs, raising blood levels and increasing the risk of side effects.
• Seek emergency care for priapism. A sustained erection lasting longer than 4 hours requires immediate medical attention. Untreated priapism can cause permanent tissue damage.
• Never combine with nitrates. Patients need to understand this applies to all forms of nitrates, not just prescription nitroglycerin.

Lifestyle modifications for BPH symptom management:

• Limit fluid intake before bedtime
• Practice double voiding (urinate, wait a moment, then try again) before sleep
• Reduce caffeine and alcohol, both of which can irritate the bladder
• Perform pelvic floor exercises (Kegels) to improve bladder control

Emphasize the importance of regular follow-up appointments to monitor how well the therapy is working and to adjust dosing if needed.