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 inhibitor: Papaverine
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.
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