BPH and ED Pharmacology Flashcards
What are the 3 different MOA classes used to treat BPH?
a1-adrenergic receptor antagonists
Steroid 5a-reductase inhibitors
PDE-5 inhibitors
What are the 2 different MOA classes used to treat ED?
PDE-5 inhibitors
PGE1 agonists
5 a1-adrenergic receptor antagonist drug names
Terazosin Doxazosin Tamsulosin Silodosin Alfuzosin
-zosin
What is the goal of a1-adrenergic receptor antagonists?
When does relief occur?
Relax muscle tone
Rapid relief (days)
What a1 subtypes do a1-adrenergic receptor antagonists act on?
Prostate
Detrusor m.
SC
Prostate - a1A
Detrusor m. - a1D>a1A
SC - a1D
What happens when a1A receptors in the bladder are activated by NE?
Muscle contracts -> bladder outlet obstruction
What happens when a1D receptors in the bladder are activated by NE?
Destrusor instability -> start and stop feeling
What happens when a1 antagonists compete with NE? (3)
Reduce spasm
Promote muscle relaxation
Improve urine flow
Which 2 a1-adrenergic receptor antagonist drugs have a greater specificity for a1»>a2?
Terazosin
Doxazosin
Which 2 a1-adrenergic receptor antagonist drugs have a1A=a1D specificity?
Tamsulosin
Silodosin
Which a1-adrenergic receptor antagonist drug is non-specific a1 selective?
Alfuzosin
What are the adverse effects of terazosin and doxazosin?
Postural HypoTN
DIzziness
Fatigue
What are the adverse effects of tamsulosin and silodosin?
Reduced ejaculate
IFIS
What is an adverse effect of alfuzosin?
QT prolongation
What drug interaction is common to all a1-adrenergic receptor antagonists?
PDE-5 inhibitors (sildenafil, vardenafil)
Increased concentration of CYP 34A substrates is a common drug interaction with which 3 BPH meds?
Tamsulosin
Silodosin
Alfuzosin
Which a1-adrenergic receptor antagonist has an approved generic?
Tamsulosin
2 steroid 5a reductase inhibitors
Finasteride
Dutasteride
What is the overall MOA for 5a reductase inhibitors?
To decrease prostate size and inhibit enlargement
How long does it take 5a reductase inhibitos to work?
3-6 mo. It is a delayed action.
What causes the prostate to enlarge?
What is a SARs role in this?
T and DHT (DHT is 10x more potent than its T precursor).
SARs inhibit T’c conversion to DHT.
What type of SAR does a prostate that has undergone hyperplasia have?
SAR-2
2 direct effects of SAR inhibitors
2 indirect effects
Direct: T accumulation, DHT depletion
Indirect: androgen receptor is less occupied, no gene transcription occurs
Finasteride targets which SAR?
Dutasteride?
Finasteride: SAR-2
Dutasteride: SAR-1,2 (dual inhibitor, thus will lead to less serum DHT (70% reduction for Fin. and 90% reduction for Dut.))
Possible S/E for pts. on SAR inhibitors
ED
Gynecomastia
Dec. libido
Ejaculation disturbances
SAR inhibitors do not require _______ for age or renal problems.
Are there significant drug interactions?
Which pts. should be cautioned to use it?
Dosage adjustments
No
Pts. w/ liver disease -> metabolized by CYP3A
When should combo Tx of SAR inhibitors and a1 adrenergic antagonists be used?
Severe sx of BPH
Known large prostate
No response to monotherapy
What drug is the lone PDE-5 inhibitor to treat BPH?
Why should it be given?
Tadalafil
If pt. has BPH and ED.
Risk factors for ED
Obesity
Smoking
Stress
What is the normal physiologic pathway to an achieve an erection?
Where does PDE-5 come into play?
L-Arg (via NOS) -> NO -> cGMP -> + Ca2+ -> SM relaxes -> erection.
PDE-5 turns cGMP into 5’-GMP and slows the process.
What kind of inhibition do PDE-5 inhibitors use to inhibit PDE-5?
Competitive
4 PDE-5 inhibitors to know
Sildefanil (Viagra)
Vardenafil (Levitra)
Tadalafil (Cialis)
Avanafil (Stendra)
Which PDE-5 inhibitor has the fastest onset?
Avanafil
Which PDE-5 inhibitor has the longest duration of action?
Tadalafil
S/E of PDE-5 inhibitors
Mild.
HA, dyspepsia, nasal congestion.
Blurred vision (Sildenafil, vardenafil, avanafil)
Back pain, myalgia (Tadalafil)
Most major contraindication to a patient taking a PDE-5 inhibitor:
Organic nitrates
How does Alprostadil treat ED?
It is PGE1 and is injected in an effect to increase cAMP levels to achieve an erection.
*PGE1 agonist
Why is an erection > 4 hrs. an issue?
Tx?
Blood may be clogged in penis and lead to corporal fibrosis and permanent ED (more common to Alprostadil).
Phenylephrine (a sympathomimetic) and aspiration
