WEEK 9 ERECTILE DISFUNCTION

Question 1

Recognize the pathophysiology of erections and how PDE-5 inhibitors influence the pathway to treat erectile dysfunction.

Answer 1

-Normal erections require a complex interaction between hormonal, vascular, neurological and psychological systems -Risk factors for ED include chronic illnesses such as DM, HTN, obesity, dyslipidemia, CVD, renal failure and liver disease.

Question 2

Medications that may cause ED:

Answer 2

Antihypertensives-change vascular tone (ACE-I, ARBs preferred)

Antidepressants (Buproprion lowest incidence) Antipyschotics: block dopamine

Anticonvulsants: CYP3A4 mediated androgen metabolism

5 alpha reductase inhibitors: decrease levels and inhibit action of dihydrotestosterone

Opioids: decrease testosterone release (tramadol may have lowest incidence)

Question 3

Describe the differences between the various PDE-5 inhibitors.

Answer 3

Note all have equal efficacy: the main difference is duration of action

• *Sidenafil** 20 mg tablet (generic): low-cost. 2-5 tablets PRN 1-4 hours prior to sexual activity, up to once daily.
• *Viagra (sidenafil)**: 25, 50, & 100 mg tablets; Initial dose 50 mg. Take 1 dose as needed 1-4 hours prior to sexual activity (max once daily). Decrease dose to 25 mg in people with renal impairment or hepatic disease.
• *tadalafil (Cialis):** 2.5, 5, 10, 20 mg tablets; PRN dosing. Initial dose 10 mg. Take 1 dose PRN for sexual activity. May increase dose to 20 mg. May last up to 36 hours. Higher dose should not be used daily. (Daily dosing is 2.5-5 mg same time everyday).
• *vardenafil (Levitra):** 2.5, 5, 10, 20 mg tablets; Initial dose 10 mg. Take 1 dose PRN 1-4 hours before sexual activity once daily. Decrease dose to 5 mg in pts with hepatic or renal impairment or coadministration with CYP3A4 inhibitors.

Question 4

MOA, metabolism, adverse effects of PDE-5 inhibitors:

Answer 4

MOA: inhibit breakdown of GMP
PDE-5 Inhibitors are facilitators, not initiators (sexual stimulation is still neeed).
Note: tadalafil also approved for irritative symptoms of benign prostatic hyperplasia (BPH)
Metabolism: All are metabolized by CYP3A4 inhibitors and alpha antagonists.

• *Adverse Effects:** Headache, flushing hypotension
• *Precautions**: Contraindicated with use of nitrates (hypotension), priaprism (rare), visual disturbances (rare), sudden hearing loss (rare)

Question 5

Drug interactions with PDE-5 inhibitors

Answer 5

• Nitrates
• Alpha I antagonists (e.g., doxazosin, terazosin) increased risk of hypotension
• CYP3A4 inhibitors (e.g., ketaconazole)
• Antiarrhythmic agents (e.g., vardenafil)-QT prolongation.

Question 6

Non-pharmacologic ED treatment

Answer 6

Lifestyle modifications, psychotherapy, medical devices (vacuum erection devices;VEDs), surgery: prosthesis, malleable inflatable rods, penile revascularization

Question 7

Role of prostaglandin analogs in treatment of ED:

Answer 7

Question 8

Role of testosterone in the treatment of ED:

Answer 8