From the Guidelines
Tadalafil treats erectile dysfunction by inhibiting the enzyme phosphodiesterase type 5 (PDE5), which helps men achieve and maintain erections. When sexually stimulated, the body releases nitric oxide in the penis, activating an enzyme called guanylate cyclase that produces cyclic guanosine monophosphate (cGMP) 1. This cGMP relaxes smooth muscles in penile blood vessels, allowing increased blood flow and producing an erection. Normally, PDE5 breaks down cGMP, but tadalafil blocks this enzyme, maintaining higher cGMP levels and prolonging the erection.
Key Points
- Tadalafil is typically taken at doses of 5-20mg as needed before sexual activity, with effects lasting up to 36 hours, earning it the nickname "weekend pill" 1.
- For daily use, lower doses of 2.5-5mg are prescribed.
- Unlike other ED medications, tadalafil works only with sexual stimulation and won't cause spontaneous erections.
- It should not be taken with nitrate medications as this combination can cause dangerous drops in blood pressure.
- Common side effects include headache, indigestion, back pain, muscle aches, flushing, and nasal congestion.
Evidence
High-quality evidence indicated that all 5 agents (sildenafil, vardenafil, tadalafil, mirodenafil, and udenafil) improved erections (range, 73% to 88%) compared with placebo (range, 26% to 32%) 1. The most recent and highest quality study, published in 2018, recommends that men with ED should be informed regarding the treatment option of an FDA-approved oral phosphodiesterase type 5 inhibitor (PDE5i), including discussion of benefits and risks/burdens, unless contraindicated 1.
Recommendations
The American College of Physicians recommends that clinicians initiate therapy with a PDE-5 inhibitor in men who seek treatment for erectile dysfunction and who do not have a contraindication to PDE-5 inhibitor use 1. The choice of a specific PDE-5 inhibitor should be based on the individual preferences of men with erectile dysfunction, including ease of use, cost of medication, and adverse effects profile 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 Because sexual stimulation is required to initiate the local release of nitric oxide, the inhibition of PDE5 by tadalafil has no effect in the absence of sexual stimulation.
Tadalafil works for ED by inhibiting the enzyme phosphodiesterase type 5 (PDE5), which increases the amount of cyclic guanosine monophosphate (cGMP) in the smooth muscle cells of the corpus cavernosum. This increase in cGMP leads to smooth muscle relaxation, increased blood flow into the corpus cavernosum, and ultimately, an erection.
- Key points:
- Tadalafil inhibits PDE5
- Increased cGMP levels lead to smooth muscle relaxation
- Increased blood flow into the corpus cavernosum results in an erection
- Sexual stimulation is required for tadalafil to work 2
From the Research
Mechanism of Action
- Tadalafil, a phosphodiesterase type 5 (PDE5) inhibitor, works by mediating relaxation of vascular smooth muscle in the corpus cavernosum, thus facilitating erection 3.
Efficacy in Erectile Dysfunction (ED)
- Tadalafil has been shown to improve erectile function in men with ED, with significant increases in successful intercourse attempts compared to placebo 4, 3, 5.
- The efficacy of tadalafil has been demonstrated in various clinical populations, including patients with different demographics, ED characteristics, and comorbid medical conditions 6.
On-Demand and Daily Dosing
- Tadalafil has been shown to be effective when taken on-demand, with improved erectile function up to 36 hours after dosing 4, 5.
- Daily dosing of tadalafil has also been shown to improve erectile function, with a higher percentage of patients achieving normal erectile function compared to placebo 7.
Treatment Satisfaction
- Tadalafil has been shown to demonstrate superior treatment satisfaction relative to placebo, with a higher percentage of patients reporting satisfaction with treatment 3.