Penile Erection Dysfunction Drugs

Question 1

Types of Penile Erection Dysfunction Drugs

Answer 1

• Alprostadil (Caverjet)- prostoglandin that relax vascular smooth muscles and allows filling of corpus cavernosum when injected directly into the cavernosum
• Sildenafil (Viagra)
• Tadalafil (Cialis)
• Vardenafil (Levitra) - selectively inhibits enzyme called phosphodiesterise type 5 enzyme (PDE5) and increase nitric oxide levels allowing blood to flow in the corpus cavernosum

These drugs have the advantage of oral drugs that can be timed in coordination with sexual activity based on onset

Question 2

Therapeutic Use & Indication

Answer 2

• The prostoglandin alprostadil is injected and act locally to relax vascular smooth muscles and allows filling of corpus cavernosum (penile erection)
• Metabolized to inactive compounds in liver excreted in urine
• Not for pregnant and lactating women
• PDE5 are taken orally and act to increase nitric oxide levels allowing blood to flow in the corpus cavernosum
• Nitric oxide activates the enzyme guanylate cyclase whic h then stimulates the release of cGMP causing an smooth muscle relaxtion allowing blood to flow to corpus cavernosum
• The inibitors prevent the breakdown of cGMP by phosphodiesterase leading to increased cGMP levels and prolonged smooth muscle relaxtion allowing blood to flow to corpus cavernosum
• Sildenafil - treats pulmonary arterial hypertension, relax smooth muscles, pulmonary artery relaxes- less resistance and pressurre in pulmonary bed

If alprostadil is being used condoms should be used with a pregnant woma

Question 3

Pharmacokinetics

Answer 3

• Well absorbed from GIT
• Metabolized in liver and excreted in feces
• Sildenafil : onset- 27 mins; duration- 4hrs (pt encouraged to take drug 1hr before anticipated sexual stimulation);
• Vardenafil : onset- 26 mins; duration 4hrs ( take 1 hr before sexual stimulation)
• Tadalafil : onset- 45 mins; duration - 36hrs (take if timing of sex unknown)

Question 4

Comparison

Answer 4

• Tadalafil has the longest period of onset and lasts up to 3 hrs where as sildenafil is effective up to 12 hrs and vardenafil is only effective 4- hrs after administration
• Vardenafil if the most potent (lowest maximal concentration) and bind to PDE5 more rapidly that the others thus it has a potential time of onsent of mins.

Question 5

Contraindication

Answer 5

• Conditions predisposed to priapism ( sickle cell anemia negates priapism due to abnormal blood flow)
• Cannot be used with penile implants
• Not for use in women (only for pulmonary arterial hypertion treatment)
• Caution in patients with bleeding disorders
• PDE5 inhibitors used cautiosly with patients with coronary artery disease, hypotension, severe hepatic/ renal disorders

Question 6

Drug Interactions

Answer 6

• PDE5 drugs cannot be taken with organic nitrates (nitroglycerin)
• Alpha - adrenergic blockers abd beta-adrenergic blockers serious cardiovascular effects (hypotensive)
• Medications - a-blocker (tamsulosin) b-blocker(carvedilol)
• Vardenafil, tadalafil, increase serum levels with indinavir, ritonavir (anit-retroviral), ketoconazole, itraconazole

Question 7

Adverse Effects

Answer 7

• Headache
• Abnormal vision
• Urinary tract infection

Question 8

Implications

Answer 8

• Assess cause of dysfunction
• Patient teaching
• Monitor patients with vascular disease
• Monitor nitrates use, a-blockers, b-blockers
• Monitor endocrine function, hepactic & serum electrolyte before, during therapy (dosage adjustment, severe effect can be avoided)