Erectile Dysfunction

ERECTILE DYSFUNCTION


ERECTILE DYSFUNCTION (ED)

  • 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.

Etiology:

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.,

MANAGEMENT:

I) MAIN ORAL THERAPY:

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:

Sildenafil-

    • 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.

II). OTHER ORAL DRUGS:

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.

II). INTRACAVERNOSAL INJECTION THERAPY:

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

ERECTILE DYSFUNCTION

  • 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.

 

Don’t Forget to Solve all the previous Year Question asked on ERECTILE DYSFUNCTION

Module Below Start Quiz

This site uses Akismet to reduce spam. Learn how your comment data is processed.

%d bloggers like this:
Malcare WordPress Security