Erectile Dysfunction



  • Condition in which there is an inability for a male to attain & maintain penile erection for sufficient duration that allows satisfactory intercourse.

Physiology of penile erection:

  • Normal penis erection requires parasympathetic system (S2-4), nitric oxide (NO) synthesis & normal release process.
  • NO increases cGMP levels (Most important step is metabolized by phosphodiesterase) –> smooth muscles relaxation of corpora cavernosa –> Penile erection.
  • Penis erection requires increased blood supply by vasodilatation.

Pharmacological basis:

  • Drugs producing these effects & enhancing penile erection are,
    • Phosphodiesterase inhibitors
    • α-blockers
    • PGE-2 & PGI-2 – By increasing sperm motility.


1. Primary causes:

  • Psychological – Most common
  • Vascular
  • Neurological
  • Hormonal

2. Secondary causes:

  • Arteriosclerosis
  • Hypertension
  • Diabetes
  • Smoking
  • Alcohol consumption
  • Drugs:
    • Maximum – Diuretics (Thiazide)
    • Others risky drugs – Alpha agonists (Phenylephrine), Beta blockers, CCB’s etc.,



1. Phosphodiesterase inhibitors:

  • MOA – 
    • Normally, cGMP formed by NO action is metabolized by phosphodiesterase
  • Drugs included – 
    • Sildenafil, vardenafil, udenafil, avanafil, tadalafil & papaverine.
  • Disadvantages – 
    • Not to be prescribed for patients on nitrates, due to severe hypotension risk.

Important phosphodiesterase inhibitors:


    • Selectively inhibits PDE-5 –> Increases cGMP levels – Hence, effective drug.
    • Orally administered.
  • Uses –
    • ED & pulmonary hypertension management.
  • Adverse effects – 
    • Visual disturbances (blue vision).
    • Color vision defect – Due to PDE-6 inhibition present in retina.
  • Other effects – Headache, nasal congestion & flushing.
Other drugs:
  • Tadalafil – Longest acting phosphodiesterase inhibitor.
  • Avanafil – New drug for ED.
  • Papaverine – Non-selective PDE inhibitor.


1. Dopamine agonist:

  • Apomorphine – D1 agonist.
  • Used sublingually.
  • Main adverse effect – Nausea.

2. α-blocker drugs:

  • α1 and α2 blocker (Non-selective α-inhibitor) – Phentolamine.
  • α2 blocker – Yohimbine.

3. NO precursor: L-arginine

4. Antidepressants: Trazodone

5. Restoration for erectile function: Naltrexone.

6. Herbal drugs:

  • Ginseng, kava & gingko.
  • Efficacy unestablished clinically.

7. Combination drugs:

  • Trazodone (an antidepressant) & phentolamine (non-selective α blocker) combination.


1. PGE analogue:

  • Alprostadil (PGE1 analogue)
  • Administered directly in cavernosal tissue.
  • More useful in patients unresponsive to oral sildenafil therapy.

2. α-blocker drugs:

  • Thymoxamine & Phentolamine – As intracavernosal injections.
  • Phentolamine – Non-selective α-blocker.
  • Thymoxamine – α-blocker with vaso-dilatory property.

3. Non-selective PDE inhibitorPapaverine

4. VIP analog:

  • Aviptadil – Causes smooth muscle relaxation.
  • Also, used in combination with phentolamine.

5. Combination drugs:

  • Ketanserin (5-HT2) & alprostadil (α-receptor antagonist) combination.

Exam Important


  • Nitric oxide (NO) increases cGMP levels (This most important step is metabolized by phosphodiesterase) → smooth muscles relaxation of corpora cavernosa –> Penile erection.
  • Primary & most common cause for ED is psychological.
  • Secondary causes for ED include arteriosclerosis, hypertension, diabetes, smoking & alcohol consumption.
  • Diuretics have the maximum risk factor for causing ED.
  • Alpha agonists (Phenylephrine), Beta blockers, CCB’s also cause erectile dysfunction.
  • Phosphodiesterase (PDE) inhibitors are the mainstay for treating erectile dysfunction.
  • PDE inhibitors include drugs like Sildenafil, vardenafil, udenafil, avanafil, tadalafil & Papaverine.
  • Main mechanism behind PDE inhibitors is by blocking PDE enzyme, which metabolizes cGMP formation by NO
  • Phosphodiesterase inhibitors are not to be prescribed for patients on nitrates, due to severe hypotension risk.
  • Sildenafil selectively inhibits PDE-5 & increases cGMP levels.
  • Sildenafil causes color vision defect (blue vision), due to inhibition of PDE-6, present in retina.
  • Tadalafil is the longest acting phosphodiesterase inhibitor.
  • Avanafil is the new drug for ED.
  • Papaverine is a non-selective PDE inhibitor used for treating ED.
  • Apomorphine is a dopamine (D1) agonist, given sublingually for treating ED.
  • Phentolamine is an α1 and α2 blocker (Non-selective), used for treating erectile dysfunction.
  • Yohimbine is an α2 blocker, used for treating erectile dysfunction.
  • L-arginine is a NO precursor used for treating ED.
  • Trazodone is an anti-depressant used for treating ED.
  • Combination of Trazodone (an antidepressant) & phentolamine (non-selective α blocker) is used for treating ED.
  • Intracavernosal injection therapy includes usage of PGE analogs, α-blockers, non-selective PDE inhibitors & VIP analogs.
  • Ketanserin (5-HT2) & alprostadil (α-receptor antagonist) combination is given intracavernosal for treating ED.
  • Papaverine is a non-selective PDE inhibitor used for treating ED.
  • Thymoxamine & Phentolamine are given as intracavernosal injections, for treating ED.
  • Thymoxamine is used for treating ED, mainly by acting as α-blocker with vaso-dilatory property.
  • Alprostadil is a PGE1 analog, given directly in cavernosal tissue, for persons unresponsive to oral sildenafil therapy during ED treatment.


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