Lecture 2: Male GU Pharm

Question 1

Which α receptor is on the detrusor m. and when stimulated by NE can lead to detrusor instability?

Answer 1

α1D

Question 2

Which α receptor subtype is found on prostate smooth muscle and is resposnsible for contraction when stimulated by NE?

Answer 2

α1A

Question 3

Which two α1 receptor antagonists used in BPH are selective for the α1 >>>> α2 receptor?

Answer 3

1. Terazosin
2. Doxazosin

Question 4

What are the AE’s associated w/ terazosin and doxazosin used to treat BPH?

Answer 4

Postural hypotension, dizziness, fatigue –> α1 receptor antagonists

Question 5

Which two α1 receptor antagonists used for BPH are uroselective and bind α1A = α1D?

Answer 5

1) Tamsulosin
2) Silodosin

Question 6

What are the AE’s associated with tamsulosin and silodosin used for BPH?

Answer 6

• Reduced ejaculation
• IFIS = intraoperative floppy iris syndrome

Question 7

Which α1 receptor antagonist has functional uroselectivity and is used to treat BPH?

Answer 7

Alfuzosin

Question 8

What is a serious AE associated with Alfuzosin used in treatment of BPH?

Answer 8

QT prolongation

Question 9

Which three α1 receptor antagonists used in BPH increase the concentration of CYP3A4 substrates?

Answer 9

• Tamsulosin
• Silodosin
• Alfuzosin

Question 10

What is the best monotherapy for prompt relief of BPH symptoms (days)?

Answer 10

α1 receptor antagonists

Question 11

Alfuzosin should not be given to tx BPH in patients with what impairment?

Answer 11

Hepatic impairment

Question 12

What are the two steroid 5α-reductase inhibitors used for BPH?

How quickly do they work?

Answer 12

• Finasteride and Dutasteride
• Delayed action –> shrinkage and sx relief in 3-6 months

Question 13

What are the direct effects (MOA) of steroid 5α reductase inhibitors?

Answer 13

• Directly inhibit production of DHT in prostate epithelial cells
• Cause TestosteroneaccumulationandDHT depletion

Question 14

Which steroid 5α reductase inhibitor is specific for SAR-2?

Answer 14

Finasteride = SpeciFIc inhibitor of SAR-2

Question 15

Which steroid 5α-reductase inhibitor is a dual inhibitor of both SAR-1 and 2?

Answer 15

Dunasteride = DUal inhibitor

Question 16

Which steroid 5α-reductase (SAR) is most implicated in BPH and is seen in excess in a hyperplastic prostate?

Answer 16

SAR-2

Question 17

Which steroid 5α-reductase inhibitor causes the greatest (90%) decrease in serum DHT?

Answer 17

Dutasteride

Question 18

What are 4 AE’s associated with the steroid 5α-reductase inhibitors used for BPH?

Answer 18

1. Erectile dysfunction
2. Gynecomastia
3. Depressed libido
4. Ejaculation dysfunction

Question 19

Caution should be taken when using 5α-reductase inhibitors in pts with what?

Answer 19

Liver abnormalities –> metabolized by hepatic CYP3A

Question 20

Which PDE-5 inhibitor is now approved by the FDA to treat BPH as well as erectile dysfunction?

Answer 20

Tadalafil

Question 21

Which PDE-5 inhibitor can be taken 15 mins prior (high dose) or 30 mins prior (normal dose) for ED?

Answer 21

Avanafil

Question 22

What are 2 AE’s of the PDE-5 inhibitors sildenafil, vardenafil, and avanafil due to binding PDE-6 in the retina at high doses?

Answer 22

• Blue vision
• Blurred vision

Question 23

What are 3 less common AE’s specific to tadalafil?

Answer 23

• Back pain
• Myalgia
• Limb pain

Question 24

What is a major contraindication for PDE-5 inhibitors?

Why?

Answer 24

• Organic nitrates
• Extreme and dangerous hypotension

Question 25

If using tadalafil for BPH, what should not be used at the same time?

Answer 25

Concurrent α1-blockers

Question 26

Patients need to be what before starting vardenafil?

Answer 26

Hemodynamically stable

Question 27

What are 2 second-line ED therapies?

Answer 27

- **Vacuum erection** devices - Penile injections w/ **alprostadil** --\> PGE 1 agonist

Question 28

What is the MOA of Alprostadil?

Answer 28

- Leads to increases in cAMP - Decreases in iCa²⁺ - Smooth muscle relaxation - Erection

Question 29

What is a serious AE of Alprostadil used as an alternative ED tx? How does it need to be dealt with or can progress to what?

Answer 29

- Prolonged erection (priapism) - Medical emergency! Need to evacuate clogged blood - Can result in **permanent corporal fibrosis** and **ED**

Question 30

What is the pharmacological treatment for prolonged erection (priapism)?

Answer 30

Sympathomimetic (phenylephrine) + aspiration

Question 31

What is recommended for using Sildenafil for ED and a concurrent α1-blocker for BPH?

Answer 31

Concurrent α-blockers initiated at **lowest recommended dose**