Drugs in Prostate Disease and Erectile Dysfunction

Question 1

Three regions of the prostate and which are most affected by benign and malignant disease?

Answer 1

Transition zone: surrounds the urethra

• Benign prostatic hyperplasia, 20% of prostate cacner

Peripheral zone: Most of prostate:

• 70% of cancers

Central zone

Question 2

What drives development of the prostate?

Answer 2

5-alpha-dihydrotestosterone (DHT)

Question 3

What is benign prostate hyperplasia?

What type of tissue does it involve?

Answer 3

Androgen dependent overgrowth of BOTH epithelial and fibromuscular tissue of the prostate.

Question 4

Does benign prostatic hyperplasia pre-dispose to prostate cancer?

Answer 4

No

Question 5

True or false: 10% of men will develop benign prostatic hyperplasia by age 60.

Answer 5

False - 50% of men will have BPH by age 60.

Question 6

Symptoms of benign prostate hyperplasia

Answer 6

Obstructive symptoms:

• Decrease force of urinary stream
• Hesistancy in initiation of urination
• Dribbling post-voiding

Irritative symptoms:

• Dysuria
• Frequency
• Urgency
• Nocturia

Question 7

What are the two mechanisms of symptoms of BPH?

Answer 7

1. Obstructive symptoms from pressure of enlarged prostate against urethra
2. Dynamic obstruction - tension of smooth muscle mediated by α1-adrenergic receptors contribute to both obstructive and irritative symptoms

Question 8

What adrenergic drugs help to relieve irritative and obstructive symptoms?

Answer 8

α1-adrenergic receptor blockers

Question 9

Give two examples of alpha adrenergic blockers used in treatment of BPH

Answer 9

Selective α1-adrenergic blockers:

• Terazosin
• Tamsulosin (best)

Question 10

Besides α1-adrenergic blocking, what else is done to treat BPH?

Give two examples

Answer 10

5α-reductase inhibition:

• Finasteride
• Dutasteride

Question 11

Side effects of α1-adrenergic blockers?

Answer 11

• Postural hypotension
• Headache
• Ejaculatory dysfunction

Question 12

What indicates which treatment to use on BPH?

Answer 12

Severity of symptoms

Use α1-adrenergic blockers if prostate volume is <30mL

Use 5α-reductase inhibitors in moderate to severe symptoms.

Question 13

What benefits do 5α-reductase inhibitors have?

Answer 13

• More effective in larger prostates
• Reduce prostate volume
• Improve symptoms
• Reduce disease progression

Question 14

Which drug is more effective in combination with tamsulosin?

Answer 14

Dutasteride

Question 15

Adverse sexual effects of 5α-reductase inhibitors

Answer 15

• Erectile dysfunction
• REduced libido
• Gynaecomastia

Question 16

Two strategies in hormonal therapy in prostate cancer.

Example for each

Answer 16

1. Androgen receptor antagonist (Flutamide)
2. Androgen production inhibition (GnRH AGONIST - Goserelin)

Question 17

What is the concept of ‘total androgen blockade’

Answer 17

Combination of a GnRH agonist with an androgen receptor antagonist.

Provides maximal blockade of androgen receptor activation

Question 18

Side effects of androgen receptor antagonism?

Answer 18

Similar to 5α-reductase inhibiton S/E:

• Gynaecomastia
• Reduced libida
• Reduced facial and body hair

Question 19

What is the action of cyproterone acetate?

Answer 19

Dual action:

• Competes with DHT for androgen receptor (partial agonist)
• Suppresses GnRH secretion

Question 20

What do phosphodiesterase (PDE-5) inhibitors do?

Give two examples.

Answer 20

PDE-5 breaks down cGMP, the messenger of NO.

Prevention of cGMP breakdown → increase smooth muscle relaxation → increased vascular engorgement

Exmaples:

• Sildenafil (Viagra)
• Vardenafil (Levitra)

Question 21

S/E of PDE-5 inhibitors

Answer 21

• Headache
• Nasal congestion
• Facial flushing

Question 22

Contraindications for PDE-5 inhibitor use

Answer 22

• Men on nitrate drugs for heart disease - severe hypotension risk
• Severe postural hypotension