Drug Treatment of Urogenital Disease

Question 1

Define erectile dysfunction.

Answer 1

Persistent inability to achieve or maintain erection sufficient for satisfactory penetration of sexual satisfaction

Question 2

Stats about erectile dysfunction?

Answer 2

Age related; 39% men>40yrs, 55% men>70yrs.

Psychogenic, organic of mixed aetiology.

Question 3

What are risk factors for erectile dysfunction?

Answer 3

1) Disease - diabetes, CV disease (interact with vascular function), depression (psychogenic)
2) Drugs - alcohol, thiazides, antidepressants, sedatives.
3) Trauma - spinal cord injury, prostatectomy.

Question 4

Explain the physiology of an erection.

Answer 4

1) Arousal
2) Activation of parasympathetic nerves - releasing NO, causing relaxation of blood vessels.
AND…inhibition of sympathetic nerves removing NA induced (alpha1) contraction of BV.
3) Blood enters corpus cavernosum and corpus spongiosum causing them to swell; swelling occludes the venous outflow causing engorgement and erection.
4) Following orgasm, the parasympathetic nerves re inhibited and the sympathetic nerves are activated; the release of NA contracts the CC/CS and allows detumescence.

Question 5

Explain what happens at the nitergic neuroeffector junction.

Answer 5

In parasympathetic nerve: Larg –nNOS (Ca++ dependant)–> Lcit + NO…. NO to smooth muscle and activate guanylyl cyclase. GTP –gunaylyl cyclase–> cGMP which causes relaxation. cGMP is broken down to GMP by PDE5.

Question 6

Viagra?

Answer 6

Orally effective.
Selective PDE5 inhibitor.
Requires sexual arousal to provide effect
Pleak plasma levels after 30-120mins
25-100mg, 1hr, prior to sex.
t1/2 = 4 hours
metabolised by cytP450
SIDE EFFECTS: visual disturbances/blue tinge (PDE6), headache, flushing, nitrate interactions.

Question 7

What are 2 newer PDE5 inhibitors?

Answer 7

Vardenafil, tadalafil.

Question 8

PGE1 (alprostadil)?

Answer 8

Vasodilator. Intracavernous injection, painful.

Question 9

Papaverin?

Answer 9

Vasodilator, weak PDE inhibitor - intracevernous injection - pain at site of injection.

Question 10

Phentolamine?

Answer 10

Symptholytic - alpha antagonist!
BUT can cause Priapism. Painful, prolonged erection for more than 4 hours - if great than 6, treat…aspiration of blood, administration of sympathomimetics - phyenylephrone (alpha ag)

Question 11

Explain a central treatment for Erectile Dysfunction.

Answer 11

Apomorphine - dopamine agonist.

Sublingual administration - but vomitting.

Question 12

Give some example of female sexual dysfunction.

Answer 12

Hypoactive sexual desire, sexual arousal disorder, orgasmic disorder, sexual pain disorder.

Question 13

What is urinary incontinence?

Answer 13

Demonstrable involuntary loss of urine - affects 10% of women.

Question 14

What is stress incontinence?

Answer 14

Involuntary loss of urine in the absence of detrusor contraction.

• pressure inside the bladder > pressure applied by urethra.
• displacement of urethra downwards through the pelvic floor and out of abdomen.
• caused by weakening of pelvic floor muscles following childbirth.
• loss of urine during coughing, sneezing, laughing.

Question 15

What is urge incontinence?

Answer 15

Persistent need to urinate due to detrusor over activity (due to inflammation/irritation).

Question 16

Treatment of stress incontinence?

Answer 16

Drugs used to support non-pharmacological approaches - eg pelvic floor exercises/bladder management.

Drugs aim to increase urethral pressure.

• alpha 1 agonist - ephedrine.
• NA uptake inhibitor - duloxetine
  or. ..oestrogen therapy to build up the urethral mucosa.

Question 17

Treatment of urge incontinence?

Answer 17

Decrease detrusor activity (contracts via ACh on M3 receptors)
M3 antagosnist - oxybutnin
BUT - dry mouth, constipation, headaches and nausea.

Question 18

Explain bengin prostatic hyperplasia.

Answer 18

Most frequence cause of neoplasm - caused by excessive growth of a gland.
50+ yrs > 85%
Enlargement of prostate causes bladder outflow obstruction and decreased urine flow….or conversely - urge incontinence.

Question 19

Explain growth and contraction of the prostate.

Answer 19

Growth - androgen dependent. (DHT)

Contraction - sympathetic.

Question 20

Finasteride?

Answer 20

Inhibits 5 alpha reductase (converts testosterone to DHT). Decreases DHT levels and prostate size (20%) and decreased need for surgery by 50%!

Question 21

Prazosin?

Tamsulosin?

Answer 21

Alpha 1 antag - inhibits contraction, relieves pressure on urethra.
BUT postural hypertension, dizziness etc.

Tamsulosin - alpha 1A anta - less side effects and only take once daily!

Question 22

Why are drugs better than surgical prostatectomy?

Answer 22

Less risk of impotenence, incontinence and embolism.