What is the role of Ach in an erection?
- 1. Ach stimulates:
- Increased production of NO
- Increased cGMP conversion by guanylate cyclase
- Decreased intracellular Ca in penile Artery smooth muscle cells
- Increased blood flow
- 2. Ach stimulates:
- Increased activity of adenyl cyclase
- Increased cAMP
- Decreased intracellular Ca in penile artery smooth muscle cells
- Increased blood flow
What is the normal physiology of an erection?
- With stimulation, smooth-muscle cells relax, which allows the sinusoids to engorge with blood and causes the penis to become tumescent
- As the sinusoids expand, they compress the subtunical venous plexus, which causes an erection
What is the pathophysiology of ED?
- Insufficient relaxation of smooth-muscle cells
- Decreased sinusoid compliance
- An inadequate number of smooth-muscle cells
- Tunical degeneration (Peyronie's disease)
- Insufficient compression of the subtunical veins results in erectile dysfunction
What are the common mediations to cause ED?
What is the MOA of PDE-5 inhibitors in ED?
Increase penile cGMP, resulting in relaxation of smooth-muscle cells allowing more blood in to the corpora
What is the method of action of Alprostadil in ED?
Increases the concentration of cAMP and decreases the intracellular Ca concentration resulting in relaxation of smooth-muscle cells
What's the place in therapy for vacuum constriction devices in ED?
- For pts who do not respond to oral or injectable drug treatments
- Older pts who are married or have stable sexual relationships
What's the place in therapy for penile prosthesis implantation?
For pts who do not respond to or are not candidates for oral or injectable tx
What is the MOA of testosterone replacement regimens in ED?
- Restore serum testosterone levels to correct sx of hypogonadism
- Stimulate androgen receptors in the CNS to maintain normal sexual drive
- Stimulate NO synthaseto increase NO concentrations and the effects of PDE-5 in cavernosal tissue
What are the SE of PDE-5 Inhibitors?
- Visual blue-green haze (not tadalafil)
- Nasal congestion
- decreased BP
- Increased risk of MI
What drugs are CI with PDE-5 Inhibitors?
- fatty meals (not tadalafil)
What are the SE of Alprostadil?
- Penile ache
- Leg ache
- Burning sensation in the urethra
- Penile fibrosis
What are the counseling points that should be covered with PDE-5 Inhibitors?
- No effect on erection w/o stimulation
- Take Sildenafil on an empty stomach 2hrs before meals
- Increased success rates with sequential doses
- Take Sildenavil and Vardenafil 30-60 min before sex
- Take Tadalafil 2 hrs before sex
- Avoid nitrates
What erectile dysfunction etiologies compose organic erectile dysfunction?
- Vascular (PVD, arteriosclerosis, HTN)
- Neurologic (Spinal cord injury, Stroke, DM)
- Hormonal (aging, hypothalamia)
Why is testosterone not given orally?
- bioavailability poor