Pharmacology of Male GU Disorders

Question 1

What inhibits dihydrofolate reductase directly? What inhibits it indirectly?

Answer 1

Directly: Trimethoprim

Indirectly: Sulfamethoxazole (competes with PABA)

(TMP-SMX)

Question 2

What are the common symptoms of LUTS (lower urinary tract symptoms)

Answer 2

• Interrupted stream/dribbling
• frequency
• urgency

Question 3

What are the α1 adrenergic receptor antagonists used in the treatment of BPH (benign prostatic hypertrophy)

Answer 3

• Terazosin
• Doxazosin
• Alfuzosin
• Silodosin
• Tamsulosin

Question 4

What is the MOA of α1 adrenergic receptor antagonists?

Answer 4

relax muscle tone —> rapid relief of symptoms (days)

Question 5

What are the adrenergic subtypes? Which are specific to the prostate?

Answer 5

α1B - peripheral vascular resistnace

α1A - Prostate SM

α1D - detrusor muscle

α1D - spinal cord control of urinary function

Question 6

What normal physiologic action occurs with α1A receptor stimulation by NE?

Answer 6

Prostate smooth muscle contraction

bladder outlet obstruction

Question 7

What normal physiologic action occurs with α1D receptor stimulation by NE?

Answer 7

Detrusor instability

Question 8

What occurs with pharmacologic antagonism of α1 receptors?

Answer 8

• reduces bladder spasm
• promotes muscle relaxation
• improves urine flow

antagonists will be agents that compete with normal physiologic NE

Question 9

Describe the effects of terazosin, doxazosin, tamsulosin, silodosin, and alfuzosin on α1 adrenergic receptors

Answer 9

Antagonists

Question 10

Alfuzosin (α1 adrenergic receptor antagonist) has functional uroselectivity. What does this mean? What are the recommendations for taking this medication?

Answer 10

the drug distributes into the prostate more than the serum

• Avoid in those with hepatic impairment
• take immediately after the same meal every day

Question 11

What medication types can be used in the treatment of BPH?

Answer 11

1. α1 adrenergic receptor antagonists
2. steroid 5α-reductase inhibitors
3. PDE-5 inhibitors

Question 12

What mediation types can be used in treating erectile dysfunction?

Answer 12

1. PDE-5 inhibitors
2. PGE1 agonists

Question 13

What are the steroid 5α reductase inhibitors used in the treatment of BPH?

Answer 13

1. Finasteride
2. Dutasteride

Question 14

How quickly do steroid 5α reductase inhibitors (finasteride, dutasteride) take effect?

Answer 14

delayed action, promotes shrinkage of prostate and symptom relief over the course of 3-6 months

Question 15

what factors cause hypertrophy of the prostate in BPH?

Answer 15

Aging and dihydrotestosterone (DHT)

DHT 10x > T

Question 16

What are the direct/indirect effects of Steroid 5α reductase inhibitors?

Answer 16

Direct Effects:

• T accumulation
• DHT depletion

Indirect Effects:

• Androgen receptor not occupied
• no gene transcription

Question 17

What is the MOA of Steroid 5α reductase inhibitors (finasteride, dutasteride)?

Answer 17

inhibit SAR-1 and SAR-2

SAR-2 converts testosterone (T) to dihydrotestosterone (DHT)

DHT is 10x more potent than T and is responsible for hypertrophy of the prostate

Finasteride: specific inhibitor of SAR-2

Dutasteride: Dual inhibitor of SAR-1 & 2

Question 18

Explain what occurs with prostate DHT, PSA, Serum T, and Serum DHT with finasteride and dutasteride treatment

Answer 18

Prostate DHT - 90% decreased

PSA - 50% decreased

Serum T - 15-20% increased

Serum DHT:

• Finasteride - 70% decreased
• Dutasteride - 90% decreased (SAR-1 & 2)

Question 19

What are the AE of Steroid 5α Reductase Inhibitors?

Answer 19

• Erectile dysfunction
• Gynecomastia
• Depressed libido
• Ejaculation disturbances

Question 20

There are no dosage adjustments for age or renal insufficiency nor are there any significant drugs interactions with Steroid 5α Reductase Inhibitors (finasteride, dutasteride) what is one caution that must be considered with these drugs?

Answer 20

Use w/ caution in patients with liver abnormalities

drug is metabolized by CYP3A

Question 21

What is the one PDE-5 Inhibitor approved by the FDA for the treatment of BPH and erectile dysfunction?

Answer 21

Tadalafil

Question 22

What is the MOA of PDE-5 inhibitor?

Answer 22

cGMP is converted to 5’-GMP by PDE-5 which ends the erection

Question 23

What are the PDE-5 Inhibitors?

Answer 23

• Sildenafil (viagra)
• Vardenafil (Levitra)
• Tadalafil (Cialis) - action of 36 hours (18 hr half-life)
• Avanafil (Stendra) - can be taken 15 minutes prior

Question 24

Which PDE-5 Inhibitor has the longest duration of action and half-life?

Answer 24

Tadalafil (Cialis)

36 hours of action

18 hour half-life

Question 25

Which PDE-5 Inhibitor has the quickest onset of action with a high dose?

Answer 25

Avanfail (Stendra)

15 minutes (high dose)

30 minutes (lower dose)

Question 26

What is an AE seen with Sildenafil, vardenafil, and avanafil use?

Answer 26

Blue vision

blurred vision

With high concentrations of these drugs they stimulated PDE-6 receptors in the retina causing the symptoms above

Question 27

What is an absolute contraindication of tacking PDE-5 Inhibitors?

Answer 27

They should not be taken with organic nitrates due an extreme danger of causing hypotension

Question 28

What are second line treatments for ED?

Answer 28

1. Vacuum erection device
2. (Alprostadil) Prostaglandin E1 injection into corpus cavernosum

Question 29

What is the MOA of Alprostadil (Prostaglandin E1)?

Answer 29

Activates adenylate cyclase increasing levels of cAMP leading to an erection

Question 30

Prolonged erection (priapism) is caused by clogging of blood within the corpus cavernosum. What is the treatment?

Answer 30

Sympathomimeitc (phenylephrine) + aspiration

constriction of vascularture and removal of blood