BPH and ED Drugs

Question 1

list the alpha 1 adrenergic receptor antagonists

Answer 1

• terazosin
• doxazosin
• tamsulosin
• silodosin
• alfuzosin

Question 2

MOA of alpha 1 adrenergic receptor antagonists

Answer 2

relax muscle tone

Question 3

what receptors on the prostate control smooth muscle contraction

Answer 3

alpha1A

Question 4

what receptors on the detrusor muscle control instability

Answer 4

alpha1D

Question 5

what receptors in the spinal cord control urinary function

Answer 5

alpha1D

Question 6

how to alpha 1 antagonists mediate lower urinary tract symptoms

Answer 6

they compete with NE to:

• reduce spasm
• promote muscle relaxation
• improve urine flow

Question 7

terazosin and doxazosin are specific for what receptor

Answer 7

alpha 1

Question 8

tamsulosin and silodosin are specific for what receptor

Answer 8

alpha1A and alpha1D

Question 9

alfuzosin is specific for what receptor

Answer 9

non-specific alpha1 selective

Question 10

what alpha 1 antagonists are uroselective (selective for prostate and bladder)

Answer 10

tamsulosin
silodosin
alfuzosin (functional)

Question 11

adverse effects terazosin and doxazosin

Answer 11

postural hypotension (have pt take before bed)
dizziness
fatigue

Question 12

adverse effects tamsulosin and silodosin

Answer 12

reduced ejaculation

IFIS

Question 13

adverse effects alfuzosin

Answer 13

QT prolongation

Question 14

what do finasteride and dutasteride do

Answer 14

prevent enlargement and shrink the prostate

Question 15

compare relief of symptoms between alpha 1 antagonists and steroid 5a reductase inhibitors

Answer 15

alpha 1 antagonists: rapid relief (days)

steroid 5a reductase inhibitors: delayed action, 3-6 months

Question 16

function of steroid 5a reductase

Answer 16

convert serum testosterone to DHT in cells

Question 17

excess SAR2 (steroid 5a reductase) leads to

Answer 17

BPH

Question 18

what does finasteride target

Answer 18

SAR2 only

Question 19

what does dutasteride target

Answer 19

dual inhibitor: SAR1 and SAR2

Question 20

what SAR is more prevalent in BPH

Answer 20

SAR2

Question 21

what is the effect of finasteride and dutasteride on prostate DHT, prostate serum antigen, and serum testosterone

Answer 21

90% decrease in DHT
50% decrease in PSA
15-20% increase in T

Question 22

compare the effect of finasteride and dutasteride on serum DHT

Answer 22

finasteride: 70% decreased DHT
dutasteride: 90% decreased DHT

Question 23

adverse effects of finasteride and dutasteride

Answer 23

ED
gynecomastia
depressed libido
ejaculation disturbances

Question 24

why do you have to use caution when prescribing finasteride and dutasteride to pts with liver abnormalities

Answer 24

these drugs are metabolized by CYP3A4

Question 25

describe the pathway to an erection

Answer 25

sexual stimulation --> L-arginine stimulates NOS to release NO --> increase in cGMP --> decrease in Ca2+ --> smooth muscle relaxation --> erection

Question 26

molecular mechanism behind PDE-5 inhibition

Answer 26

PDE-5 normally degrades cGMP to 5'GMP which stops the pathway towards erection, and PDE-5 inhibitors block this to maintain the erection

Question 27

why is sildenafil an effective PDE-5 inhibitor

Answer 27

it is structurally similar to cGMP and competitively inhibits PDE-5

Question 28

compare onset between the PDE-5 inhibitors

Answer 28

all are 60mins except avanafil with is 15 min for the high dose and 30 for normal dose

Question 29

compare duration of action between the PDE-5 inhibitors

Answer 29

sildenafil: 4 hrs vardenafil: 4-5 hrs tadalafil: 36 hrs avanafil: 4 hrs

Question 30

stomach contents requirements for PDE-5 inhibitors

Answer 30

sildenafil and verdenafil: empty | tadalafil and avanafil: doesn't matter

Question 31

clearance of PDE-5 inhibitors

Answer 31

hepatic CYP3A4

Question 32

side effects PDE5 inhibitors

Answer 32

HA dyspepsia (indigestion) nasal congestion

Question 33

side effects of PDE6-related inhibitors

Answer 33

blue/blurred vision

Question 34

specific tadalafil side effects

Answer 34

back pain myalgia limb pain

Question 35

why can't you prescribe PDE-5 inhibitors to pts on organic nitrates

Answer 35

with PDE-5 inhibitors, you're preventing the breakdown of cGMP which forms from NO, if you prescribe nitrates you're going to have too much NO which will cause dangerous hypotension

Question 36

contraindications to vardenafil

Answer 36

pts needs to be hemodynamically stable

Question 37

contraindications to tadalafil

Answer 37

concurrent alpha1-blockers not recommended

Question 38

contraindications to sildenafil

Answer 38

concurrent alpha blockers initiated at lower recommended dose

Question 39

describe the mechanism for how alprostadil works

Answer 39

alprostadil stimulates PGE1 --> stimulates adenylate cyclase to increase camp --> decreases Ca2+ --> smooth muscle relaxation --> erection

Question 40

adverse effects alprostadil

Answer 40

prolonged erection