What does Tadalafil (Phosphodiesterase type 5 inhibitor) do to the body?

Effects of Tadalafil 5/10 mg on the Body

Tadalafil works primarily by inhibiting phosphodiesterase type 5 (PDE5), enhancing erectile function by increasing cGMP levels in smooth muscle, which causes relaxation and increased blood flow to the corpus cavernosum, while also improving lower urinary tract symptoms through similar mechanisms in the prostate and bladder. 1

Mechanism of Action

Tadalafil affects the body through several key mechanisms:

• Inhibition of PDE5: Tadalafil is a selective inhibitor of phosphodiesterase type 5, which is found in:

  • Corpus cavernosum (penile erectile tissue)
  • Prostate and bladder smooth muscle
  • Vascular and visceral smooth muscle
  • Other organs including kidney, lung, and heart 1

• Nitric Oxide Pathway Enhancement:

  • Sexual stimulation triggers nitric oxide release from nerve terminals and endothelial cells
  • Nitric oxide stimulates cGMP synthesis in smooth muscle cells
  • Tadalafil prevents breakdown of cGMP by inhibiting PDE5
  • Increased cGMP causes smooth muscle relaxation and increased blood flow 1

Effects on Erectile Function

Tadalafil 5-20 mg significantly improves erectile function by:

• Increasing blood flow to the penis during sexual stimulation
• Improving International Index of Erectile Function-Erectile Function (IIEF-EF) domain scores 2
• Enhancing successful sexual encounters as measured by Sexual Encounter Profile Question 3 (SEP Q3) 2
• Providing longer duration of action (up to 36 hours) compared to other PDE5 inhibitors 3

Effects on Lower Urinary Tract Symptoms (LUTS)

Tadalafil 5 mg daily has been shown to:

• Significantly improve International Prostate Symptom Score (IPSS) 4
• Reduce symptoms of benign prostatic hyperplasia (BPH) 2, 5
• Improve BPH Impact Index (BII) scores 2
• Maintain improvements in LUTS for up to one year with continued treatment 5

Cardiovascular Effects

• Blood Pressure: Tadalafil 20 mg produces minimal changes in blood pressure compared to placebo:

  • Mean maximal decrease in supine blood pressure: 1.6/0.8 mmHg (systolic/diastolic)
  • Mean maximal decrease in standing blood pressure: 0.2/4.6 mmHg (systolic/diastolic) 1
  • No significant effect on heart rate 1

• Interaction with Nitrates: Tadalafil potentiates the hypotensive effect of nitrates, creating a potentially dangerous drop in blood pressure 1, 3

Selectivity Profile

Tadalafil shows high selectivity for PDE5 compared to other phosphodiesterases:

• 10,000-fold more potent for PDE5 than for PDE1, PDE2, PDE4, and PDE7

• 10,000-fold more potent for PDE5 than for PDE3 (found in heart and blood vessels)

• 700-fold more potent for PDE5 than for PDE6 (found in retina)

• 9,000-fold more potent for PDE5 than for PDE8, PDE9, and PDE10 1

Clinical Applications

1. Erectile Dysfunction:

   • First-line treatment option as recommended by the American Urological Association 3
   • Dosing options: 5-20 mg as needed, or 2.5-5 mg daily 3

2. Lower Urinary Tract Symptoms/BPH:

   • 5 mg daily tadalafil is recommended for patients with LUTS/BPH regardless of comorbid erectile dysfunction 4
   • Should not be combined with alpha blockers for LUTS/BPH as this offers no advantage over either agent alone 4

Important Precautions

• Absolute contraindication: Concurrent use of nitrates due to risk of severe hypotension 3, 1
• Wait at least 48 hours after tadalafil before administering nitrates in emergency situations 3
• Use with caution in patients taking alpha-blockers due to potential for additive hypotensive effects 3
• Safe for patients with stable cardiovascular disease not taking nitrates 3

Side Effects

Common side effects include:

• Back pain
• Dyspepsia (indigestion)
• Headache
• Dizziness 6

These side effects are typically mild to moderate in intensity and often diminish with continued use 5.

Unique Advantages

Tadalafil offers several advantages over other treatments:

• Improves both erectile dysfunction and LUTS/BPH simultaneously in men with both conditions 2, 7
• Unlike alpha-blockers and 5-alpha reductase inhibitors which can cause sexual dysfunction, tadalafil improves sexual function 7
• Longer half-life allows for once-daily dosing and sustained effect 6