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 Causes1. Vascular– Roughly 40% of cases of ED in men over 50– Vascular problems can impede arterial blood flow into

the penis, Examples: diabetes, cardiovascular disease (hypertension ,dyslipidemia)

2. Neurological conditions– Can lead to interruption in nerve impulse – Examples: diabetic or alcoholic neuropathy

3. 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

ALTERNATE SOLUTIONS

MEDICATIONS ASSOCIATED WITH ED

ALTERNATE SOLUTIONS

Cardiovascular Antidepressants

Betablockers Hydralazine Methyldopa Alpha-blockers

ACE inhibitorsANG II inhibitorsCa++ channel blockers

SSRITricyclic antidepressantMAOI

BuproprionMirtazapine

Diuretics Antipsychotic agents

Thiazide diureticsSpironolactone

Furosemide (loop diurectics)

Conventional neurolepticsRisperidone

QuetiapineOlanzapine

Hormone agents Gastroesophageal reflux & ulcers

Anti-androgens (e.g. cyproterone)Corticosteroids

Varies depending on indication

Cimetidine Other H2 antagonist or PPI

Antiparkinsonian agents Anticonvulsants

Levodopa At the neurologist’s discretion

CarbamazepinePhenytoin

At the neurologist’s discretion

Miscellaneous:Phenothiazine antiemetics, opioids (chronic use), digoxin, ketoconazole, lithium

Drug-induced male sexual dysfunction.Pharmacist’s Letter/Prescriber’s Letter 2006; 22(9):220907.

MEDICATIONS ASSOCIATED WITH ED

Cardiovascular Antidepressants Hormone agentsBeta blockers Hydralazine Methyldopa Alpha-blockersDigoxin

SSRITCAMAOI

Anti-androgens Corticosteroids

Diuretics Antipsychotic agents GITThiazide diureticsSpironolactone

Conventional neurolepticsRisperidone

CimetidineAntiemetics,

Antiparkinsonian Anticonvulsants Miscellaneous:Levodopa Carbamazepine

PhenytoinlithiumPhenothiazine opioids (chronic use), ketoconazole

Drug-induced male sexual dysfunction.Pharmacist’s Letter/Prescriber’s Letter 2006; 22(9):220907.

Treatment Options1. PDE5 Inhibitors– Sildenafil– Varedenafil– Tadalafil

2. Centrally Acting Oral Drugs– Apomorphine

3. Intraurethral suppositories– Alprostadil

4. Intraurethal gel5. Penile injections

1. PDE5 Inhibitors• NO in the corpus cavernosum of the penis binds to

guanylate cyclase receptors, which results in increased levels of cGMP, leading to smooth muscle relaxation (vasodilation)

• Men who have erectile dysfunction often produce insufficient amounts of NO.

• The small amount of cGMP produced 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.

• All 3 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• Dyspepsia• Nasal congestion and • Impaired vision• Priapism• Severe hypotension• 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)

A. 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

menB. Papaverine– Inhibits phosphodiesterase in smooth muscle cells,

which cAMP & cGMP relaxation of vascular smooth muscles

C. 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

E. Chlorpromazine– blocker activity

GOOD LUCK