Module 3.1.1 (Drugs for BPH)

Question 1

What are examples of selective alpha-1 adrenoreceptor blockers?

Answer 1

• Alfuzosin
• Prazosin
• Silodosin
• Tamsulosin

Question 2

What are examples of 5a reductase inhibitors?

Answer 2

Finasteride = inhibits type 2 5a-reductase

Dutasteride = inhibits type 1 and type 2 5a reductase

Question 3

Bladder neck and prostate gland are innervated by ANS, what does alpha-1 stimulation do?

Answer 3

Increases smooth muscle contraction therefore it inhibits the outflow of urine

Question 4

Following on from the previous question, what is the MOA of alpha-1 blockers (APST)?

Answer 4

α1-blockers relax smooth muscle in the prostate and bladder neck –> facilitate micturition (urinating) in patients with benign prostatic hyperplasia / hypertrophy (BPH).

Blockade of postsynaptic a1-adrenoceptors

• Block alpha receptors in non-vascular smooth muscle
• Relaxes smooth muscle in bladder neck and prostate
• Reduces resistance to urine flow

Question 5

For alpha-1 blockers, which are more specific for bladder and prostate?

Answer 5

Silodosin and tamsulosin – more specific – affects bladder and prostate act on a_1a-adrenoceptors

Question 6

For alpha-1 blockers, which one is less specific and thus causes vasodilation in ateries and veins?

Answer 6

Prazosin

Question 7

True or false, a-1 blockers have very little effect on presynaptic a2-adrenoceptors therefore much less reflex tachycardia than non-selective a blockers.

Answer 7

V true

Question 8

What are the AE of a-1 blockers (APST)?

Answer 8

AE similar to phentolamine

• Orthostatic hypotension (feeling faint on standing up), dizziness, headache, weakness, fatigue, drowsiness, diarrhoea, fatigue
• Nasal congestion, urinary urgency, First dose hypotension
• Tachycardia (less than phentolamine), palpitations, blurred vision

Question 9

Where is testosterone synthesised? What is it converted to?

Answer 9

Testosterone is synthesized in the testes by the same pathways as in the ovaries.

Testosterone is converted to dihydrotestosterone (DHT) by 5α-reductase in the prostate, hair follicles, and skin.

Question 10

What are the main androgens responsible for development and progression of BPH?

Answer 10

Testosterone and DHT are main androgens responsible for this

> DHT more potent than testosterone

> DHT more than testosterone in androgenic stimulation

Question 11

If DHT formulation inhibited, what happens to the prostate?

Answer 11

If DHT formation is inhibited, there will be significant decreased androgenic stimulation in prostate –> decrease prostate growth.

Question 12

MOA of 5a-reductase inhibitors?

Answer 12

5α-reductase inhibitors downregulate prostate growth by blocking the conversion of testosterone to DHT which is the more potent stimulator of prostate enlargement

Question 13

Where are type 1 and type 2 5a reductases found?

Answer 13

Type 1 found in liver, skin. and hair

Type 2 is predominant in genital tissue and prostate

Question 14

What are the therapeutic effects of 5a-reductase inhibitors?

Answer 14

• Downregulate prostate growth
• Reduce prostate volume
• Can retard progression of BPH
• Improve urinary flow and decrease the risk of urinary retentuon

Question 15

CIR AE of 5a-reductase inhibitors

Answer 15

Common

• impotence, decreased libido, ejaculation disorder (including decreased ejaculate volume)

Infrequent

• breast tenderness or enlargement

Rare

• allergic reaction, poor semen quality, infertility, depression