Treatment of Erectile Dysfunction

Erectile Dysfunction The persistent or recurrent inability to obtain or maintain an erection sufficient for sexual activity ED can have a major impact on the quality of life and self-esteem of men who suffer from it Men often draw a link between their masculinity and their ability to have an erection This can lead also to affected relationships with partners

Erectile Dysfunction > 50% of men aged 40 – 70 will have fairly marked erectile problems Most often is due to an organic origin (up to 80%) Can also have psychogenic causes In several cases, it is both organic/psychogenic in origin  mixed-type ED

1. Main Organic Causes Vascular Roughly 40% of cases of ED in men over 50 Vascular problems can impede arterial blood flow into the penis, Examples: diabetes, hypertension, dyslipidemia Neurological conditions Can lead to interruption in nerve impulse Examples: diabetic or alcoholic neuropathy Hormone disorders ED can be due to low testosterone (hypogonadism), hyperprolactinemia, hypothyroidism, adrenal insufficiency or glucocorticoid excess.

2. Psychogenic Origin Can be cause by: Anxiety Depression or psychosis Possibly with a loss of self-esteem If causes of erectile dysfunction are completely psychological, the patient will continue to have nocturnal erections Men with psychogenic ED often lose interest in sex

MEDICATIONS ASSOCIATED WITH ED Cardiovascular Antidepressants Hormone agents Beta blockers Hydralazine Methyldopa Alpha-blockers Digoxin SSRI TCA MAOI Anti-androgens Corticosteroids Diuretics Antipsychotic agents GIT Thiazide diuretics Spironolactone Conventional neuroleptics Risperidone Cimetidine Antiemetics, Antiparkinsonian Anticonvulsants Miscellaneous: Levodopa Carbamazepine Phenytoin lithium Phenothiazine opioids (chronic use), ketoconazole

Treatment Options PDE5 Inhibitors Sildenafil Varedenafil Tadalafil Centrally Acting Oral Drugs Apomorphine Intraurethral suppositories Alprostadil Intraurethal gel Penile injections

1. PDE5 Inhibitors NO in the corpus cavernosum of the penis lead to vasodilation Men who have erectile dysfunction often produce insufficient amounts of NO. The small amount of cGMP (required for the production of NO) is being broken down at the same rate, so they cannot maintain an erection.

Theses drugs work by selectively inhibiting PDE5 (the enzyme that breaks down cGMP). This prevents the hydrolysis of cGMP, allowing cGMP to accumulate and prolong the vasodilation effect, resulting in a stronger and longer erection. These drugs work regardless of the cause of ED, but all require sexual stimulation for activation.

The figure below shows the mechanism of action of Viagra, and the other PDE5 inhibitors, on the nitric oxide cycle.

Adverse effects Headache, flushing, Severe hypotension, Dyspepsia, Impaired vision, Priapism Increased intraocular pressure Sudden hearing loss Contraindications: Hypotension and ischemic heart disease Since PDE5 inhibitors may cause transiently hypotension, organic nitrates should not be taken for at least 48 hours after taking the last dose. Using organic nitrates within this timeframe may increase the risk of life-threatening hypotension.

Viagra for women… Due to Viagra’s PDE5 inhibition it may improve vaginal engorgement and lubrication. Viagra for women is was created in 2003. 84 percent success rate of decreasing symptoms of female sexual dysfunction, but It doesn’t have FDA approval yet. Befar, the topical alprostadil cream, may be used to treat Female Sexual Arousal Disorder.  It would cause clitoral stimulation by vasodilatation.

2. Centrally Acting Oral Drugs Apomorphine is a centrally acting drug that improves erectile dysfunction by enhancing the central natural erectile signals that normally occur in the brain during sexual stimulation. It is a non-selective dopamine receptor agonist and acts mainly on dopamine D2-like receptors in the brain.

3. Intraurethral Suppository Alprostadil Prostaglandin E1 analogue which is a vasodilator A choice for people: Who do not respond to oral pills Are afraid of injections Suppository (about the size of a grain of rice) which is placed about 1 cm inside the urethra using a special applicator Advantages Gives an erection similar to penile injection therapy The head of the penis swell with Alprostadil suppositories

MUSE® Injector

4. Intraurethal Gels Gives an erection similar to penile injection therapy Possibly stronger than using MUSE® Must be kept in the fridge and has a 30 day expiry date Directions of use: Dispense in 0.2ml single use syringes Administer intraurethrally 10 – 15 minutes prior to sexual intercourse Hold penis upright for 30 seconds to allow medication to absorb Rub any excess cream over the forehead of the penis

5. Penile Injections Intracavernosal injection therapy Very safe & highly effective Around since 1983. In 1982, a French surgeon injected a vasodilator into the pelvic artery & the patient obtained an erection Shortly after, a British physician injected a drug directly into the penis

Alprostadil (Caverject)

Alprostadil Prostaglandin E -1  cAMP Vasodilator & muscle relaxant of corpus cavernosum & trabecular smooth muscle Prefilled syringe Works in 60% men with ED Will work better with milder erection problems Can cause an aching or burning penile pain in some men Papaverine Inhibits phosphodiesterase in smooth muscle cells, which  cAMP & cGMP  relaxation of vascular smooth muscles

Phentolamine Blocks -adrenergic receptors in penile blood vessels  relaxation of trabecular cavernous smooth muscles & dilatation of the penile arteries Weak erectile-promoting effect when used alone. Potentiates the effect of papaverine or PGE-1 Chlorpromazine  blocker activity

GOOD LUCK