BPH and ED Drugs Flashcards
list the alpha 1 adrenergic receptor antagonists
- terazosin
- doxazosin
- tamsulosin
- silodosin
- alfuzosin
MOA of alpha 1 adrenergic receptor antagonists
relax muscle tone
what receptors on the prostate control smooth muscle contraction
alpha1A
what receptors on the detrusor muscle control instability
alpha1D
what receptors in the spinal cord control urinary function
alpha1D
how to alpha 1 antagonists mediate lower urinary tract symptoms
they compete with NE to:
- reduce spasm
- promote muscle relaxation
- improve urine flow
terazosin and doxazosin are specific for what receptor
alpha 1
tamsulosin and silodosin are specific for what receptor
alpha1A and alpha1D
alfuzosin is specific for what receptor
non-specific alpha1 selective
what alpha 1 antagonists are uroselective (selective for prostate and bladder)
tamsulosin silodosin alfuzosin (functional)
adverse effects terazosin and doxazosin
postural hypotension (have pt take before bed)
dizziness
fatigue
adverse effects tamsulosin and silodosin
reduced ejaculation
IFIS
adverse effects alfuzosin
QT prolongation
what do finasteride and dutasteride do
prevent enlargement and shrink the prostate
compare relief of symptoms between alpha 1 antagonists and steroid 5a reductase inhibitors
alpha 1 antagonists: rapid relief (days)
steroid 5a reductase inhibitors: delayed action, 3-6 months
function of steroid 5a reductase
convert serum testosterone to DHT in cells
excess SAR2 (steroid 5a reductase) leads to
BPH
what does finasteride target
SAR2 only
what does dutasteride target
dual inhibitor: SAR1 and SAR2
what SAR is more prevalent in BPH
SAR2
what is the effect of finasteride and dutasteride on prostate DHT, prostate serum antigen, and serum testosterone
90% decrease in DHT
50% decrease in PSA
15-20% increase in T
compare the effect of finasteride and dutasteride on serum DHT
finasteride: 70% decreased DHT
dutasteride: 90% decreased DHT
adverse effects of finasteride and dutasteride
ED
gynecomastia
depressed libido
ejaculation disturbances
why do you have to use caution when prescribing finasteride and dutasteride to pts with liver abnormalities
these drugs are metabolized by CYP3A4
describe the pathway to an erection
sexual stimulation –> L-arginine stimulates NOS to release NO –> increase in cGMP –> decrease in Ca2+ –> smooth muscle relaxation –> erection
molecular mechanism behind PDE-5 inhibition
PDE-5 normally degrades cGMP to 5’GMP which stops the pathway towards erection, and PDE-5 inhibitors block this to maintain the erection
why is sildenafil an effective PDE-5 inhibitor
it is structurally similar to cGMP and competitively inhibits PDE-5
compare onset between the PDE-5 inhibitors
all are 60mins except avanafil with is 15 min for the high dose and 30 for normal dose
compare duration of action between the PDE-5 inhibitors
sildenafil: 4 hrs
vardenafil: 4-5 hrs
tadalafil: 36 hrs
avanafil: 4 hrs
stomach contents requirements for PDE-5 inhibitors
sildenafil and verdenafil: empty
tadalafil and avanafil: doesn’t matter
clearance of PDE-5 inhibitors
hepatic CYP3A4
side effects PDE5 inhibitors
HA
dyspepsia (indigestion)
nasal congestion
side effects of PDE6-related inhibitors
blue/blurred vision
specific tadalafil side effects
back pain
myalgia
limb pain
why can’t you prescribe PDE-5 inhibitors to pts on organic nitrates
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
contraindications to vardenafil
pts needs to be hemodynamically stable
contraindications to tadalafil
concurrent alpha1-blockers not recommended
contraindications to sildenafil
concurrent alpha blockers initiated at lower recommended dose
describe the mechanism for how alprostadil works
alprostadil stimulates PGE1 –> stimulates adenylate cyclase to increase camp –> decreases Ca2+ –> smooth muscle relaxation –> erection
adverse effects alprostadil
prolonged erection
