Sexual Dysfunction

Question 1

Definition of impotence?

Answer 1

Failure to attain erection of sufficient strength to carry out sexual intercourse - at least 25% of the time. PREVALENCE is HIGH (50% of men over 50)

Question 2

What’s thought to drive increased rates of impotence with older age?

Answer 2

Vascular problems.

Question 3

2 neural systems leading to erection?

Answer 3

1) Central, forebrain limbic system -> generates sexual drive
2) Maintained by circulating androgens
- Increased parasymp inflow, decreased symp outflow
- Local parasymp reflex arc in response to tactile stimuli (penis–> spinal cord–> penis)

Question 4

3 specific physiological events in the penis that cause erection?

Answer 4

1) Relaxation of helicine arteries in corpora cavernosa.
2) Relaxation of smooth muscle of trabeculae in corpora cavernosa.
3) Impeded venous drainage due to engorged corpora cavernosa.

First 2 GENERATE erection, 3rd one MAINTAINS erection

Question 5

What drives blood vessel relaxation in erectile tissue at the molecular/cellular level? (She emphasized this..)

Answer 5

NO -> guanylate cyclase -> increased cGMP -> maintains vasodilation (erection)

• NO induces local changes in blood flow
• NO comes from 2 different sources (endothelial cells and from post synaptic parasymp neurons)

Question 6

What are a few prescribed drugs that cause impotence?

Answer 6

Beta-blockers, ACEIs, anticholinergics, antihistamines, Disulfiram SSRIs, estrogens

Question 7

6+ common causes of impotance?

Answer 7

1) Prostatectomy etc. (local reflex arc interrupted by scar tissue)
2) Diabetes, hypothyroidism
3) Vascular disease
4) Chemo/radiotherapy
5) Neuro disease (MS) and trauma
6) Liver and/or renal failure

Question 8

Various ways to Dx ED?

Answer 8

Bulbocavernosis reflex test (test nerves)
Nocturnal Penile Tumescence (test for erections while sleeping)
Inject vasodilators (test for vascular cause)
Ultrasound or MR angiography
…but this isn’t commonly done.

Question 9

4 ways to treat underlying causes of ED?

Answer 9

1) Counseling if psychogenic.
2) Surgery if local abnormality (rare).
3) Adjust meds, if iatrogenic.
4) Testosterone, if androgen deficient.

Question 10

What is alprostadil? How is it given?

Answer 10

A PGE1 analogue.
Intracavernosal injection (ouch) or intrameatal suppository.

Question 11

What is the class of the drugs of choice these days for ED?

Answer 11

Oral PDE 5 inhibitors (Viagra)

Question 12

What is a PDE 5 inhibitor (Sildenafil aka Viagra) actually do?

Answer 12

Inhibits cGMP phosphodiesterase isozyme 5, which will maintain vasodilation (but will NOT initiate erection–> for that need parasympathetic activation)

Question 13

4 Important notes about the pharmokinetics of PDE 5 inhibitors?

Answer 13

1) Rapidly absorbed- rapid onset of acton
2) Concentrations peak at 30-90 minutes
3) Metabolized by CYP 3A4.*** (more likely to get priapism!)
4) Active metabolite prolongs the effect (longer half life than you’d anticipate)
5) Excreted renally

Question 14

What is complication of PDE 5 inhibitors, especially if taking drugs that compete for CYP 3A4?

Answer 14

Priapism -> ischemic pain.

Question 15

Aside from ED, what is another indication for PDE 5 inhibitors?

Answer 15

Primary Pulmonary Hypertension (shows that they’re not totally specific for erectile tissue- do work on all PDE enzymes in body)

Question 16

3 Common, less severe side effects of PDE 5 inhibitors?

Answer 16

1) Reduced esophageal motility -> reflux.
2) Altered color vision (blue green tinge)
3) Headache, flushing, rhinitis.

Question 17

3 Cardiovascular adverse effects of PDE 5 inhibitors?

Answer 17

1) Hypotension and 2) Subsequent tachycardia -> can cause stroke or MI.
3) Platelet inhibition.

Question 18

What’s one particularly fatal drug to combine with PDE 5 inhibitors?

Answer 18

Nitrates for angina. Big problem- lots of old guys with chest pain trying to get busy… Taking both can lead to severe hypotension and can be lethal.

Question 19

3 theories as to the origin of female sexual dysfunction (FSD)?

Answer 19

1) Vascular
2) Hormone
3) Dissatisfaction

Question 20

5 categories of things that cause female sexual dysfunction?

Answer 20

1) Psychological (anxiety, depression, etc.)
2) Diabetes / atherosclerosis
3) Trauma (physical)
4) Drugs (SSRIs, etc.)
5) Urinary incontinence (with associated anxiety)

Question 21

What physiological test, rarely done, can provide an objective measure of physiological arousal?

Answer 21

Measuring vaginal pH - should increase during arousal.

Question 22

Medical assessment for sexual dysfunction (i.e. things to rule out)? (4-5 things)

Answer 22

Diabetes, pituitary, thyroid disease

Neuro stuff: MS, trauma

Question 23

3 categories of treatment for female sexual dysfunction?

Answer 23

Education
Hormone Replacement Therapy (E, sometimes T)
Vascular treatment

Question 24

3 forms of vascular treatment of female sexual dysfunction?

Answer 24

PDE5 inhibitors. (esp for SSRI-induced FSD)
Clitoral vacuum pump (Eros therapy)
L-arginine topical

Question 25

How might L-arginine topical treatment work?

Answer 25

L-arginine is substrate for NO synthesis, might increased NO.
(but this is under evaluation)