From the Guidelines
Tadalafil, beyond treating erectile dysfunction, is FDA-approved for benign prostatic hyperplasia (BPH) and pulmonary arterial hypertension (PAH), and its use is supported by recent guidelines, such as those from the American Urological Association 1.
Mechanism of Action and Effects
Tadalafil works by inhibiting phosphodiesterase type 5 (PDE5), an enzyme that breaks down cyclic guanosine monophosphate (cGMP), thereby increasing cGMP levels, leading to smooth muscle relaxation and increased blood flow in specific tissues. This mechanism is crucial for its effects in treating PAH, as noted in guidelines from the European Society of Cardiology and the European Respiratory Society 1, and for BPH, as discussed in the management guidelines for lower urinary tract symptoms attributed to BPH 1.
Dosage and Administration
- For PAH, the typical dose is 40mg once daily, as supported by studies like the PHIRST trial 1.
- For BPH, the recommended dose is 5mg daily, based on guidelines that suggest discussing this option with patients, especially those with concomitant erectile dysfunction 1.
- For Raynaud's phenomenon, doses of 10-20mg daily may be used off-label, though specific guidelines may vary.
Side Effects and Precautions
Side effects include headache, muscle pain, flushing, indigestion, and nasal congestion. Tadalafil's long half-life of 17.5 hours allows for once-daily dosing, enhancing spontaneous sexual activity. However, it should not be taken with nitrates due to potentially dangerous blood pressure drops, and caution is needed with medications like alpha-blockers and antifungals that may affect its metabolism, as generally advised in the management of erectile dysfunction 1.
Clinical Considerations
The choice of tadalafil over other PDE5 inhibitors may depend on individual patient preferences, including ease of use, cost, and adverse effects profile, as recommended by the American College of Physicians 1. Given its pharmacological profile and clinical uses, tadalafil offers a valuable treatment option for several conditions beyond erectile dysfunction, with its effects and safety profile supported by recent and high-quality evidence 1.
From the FDA Drug Label
Penile erection during sexual stimulation is caused by increased penile blood flow resulting from the relaxation of penile arteries and corpus cavernosal smooth muscle. This response is mediated by the release of nitric oxide (NO) from nerve terminals and endothelial cells, which stimulates the synthesis of cGMP in smooth muscle cells Cyclic GMP causes smooth muscle relaxation and increased blood flow into the corpus cavernosum. The inhibition of phosphodiesterase type 5 (PDE5) enhances erectile function by increasing the amount of cGMP. Tadalafil inhibits PDE5 The effect of PDE5 inhibition on cGMP concentration in the corpus cavernosum and pulmonary arteries is also observed in the smooth muscle of the prostate, the bladder and their vascular supply Tadalafil is greater than 10,000-fold more potent for PDE5 than for PDE1, PDE2, PDE4, and PDE7 enzymes, which are found in the heart, brain, blood vessels, liver, leukocytes, skeletal muscle, and other organs Tadalafil is 700-fold more potent for PDE5 than for PDE6, which is found in the retina and is responsible for phototransduction. Effects on Blood Pressure Tadalafil 20 mg administered to healthy male subjects produced no significant difference compared to placebo in supine systolic and diastolic blood pressure
The known effects of Tadalafil (Cialis) beyond its primary treatment for erectile dysfunction include:
- Relaxation of smooth muscle in the prostate, bladder, and their vascular supply
- Increased blood flow into the pulmonary arteries
- Effects on blood pressure: Tadalafil can potentiate the hypotensive effect of nitrates, but has no significant effect on blood pressure when administered alone The mechanism of action of Tadalafil is through the inhibition of phosphodiesterase type 5 (PDE5), which increases the amount of cGMP, leading to smooth muscle relaxation and increased blood flow into the corpus cavernosum 2.
From the Research
Known Effects of Tadalafil Beyond Erectile Dysfunction
- Tadalafil has been shown to improve endothelial function in patients with benign prostatic hyperplasia (BPH) 3
- It is effective in treating male lower urinary tract symptoms (LUTS) associated with BPH 3, 4, 5
- Tadalafil has been approved for the treatment of pulmonary arterial hypertension (PAH) 6
- It may have potential benefits in the treatment of cardiovascular diseases, such as heart failure (HF) 6
- Tadalafil has been shown to improve ejaculatory function, erectile function, and sexual satisfaction in men with LUTS suggestive of BPH and erectile dysfunction 7
Mechanism of Action
- Tadalafil is a phosphodiesterase-5 (PDE-5) inhibitor, which induces relaxation of smooth muscle cells in the urethra, prostate, bladder neck, and blood vessels 3, 4
- The mechanism of improved LUTS is thought to be related to alterations in nitric oxide levels, Rho-associated protein kinase deactivation, and reductions in pelvic atherosclerosis 4
- Tadalafil's cardiovascular benefits may be due to its ability to improve endothelial function and reduce adverse remodeling and hypertrophy in the heart 6
Additional Benefits
- Tadalafil has been shown to improve vessels endothelial function, as measured by brachial-ankle pulse wave velocity (baPWV) and ankle brachial index (ABI) 3
- It may have a role in the prevention or treatment of heart failure, although further studies are needed to confirm this 6
- Tadalafil is generally well tolerated, with adverse events being of mild to moderate intensity 5