Lecture 2: Male GU Pharm Flashcards
Which α receptor is on the detrusor m. and when stimulated by NE can lead to detrusor instability?
α1D
Which α receptor subtype is found on prostate smooth muscle and is resposnsible for contraction when stimulated by NE?
α1A
Which two α1 receptor antagonists used in BPH are selective for the α1 >>>> α2 receptor?
- Terazosin
- Doxazosin
What are the AE’s associated w/ terazosin and doxazosin used to treat BPH?
Postural hypotension, dizziness, fatigue –> α1 receptor antagonists
Which two α1 receptor antagonists used for BPH are uroselective and bind α1A = α1D?
1) Tamsulosin
2) Silodosin
What are the AE’s associated with tamsulosin and silodosin used for BPH?
- Reduced ejaculation
- IFIS = intraoperative floppy iris syndrome
Which α1 receptor antagonist has functional uroselectivity and is used to treat BPH?
Alfuzosin
What is a serious AE associated with Alfuzosin used in treatment of BPH?
QT prolongation
Which three α1 receptor antagonists used in BPH increase the concentration of CYP3A4 substrates?
- Tamsulosin
- Silodosin
- Alfuzosin
What is the best monotherapy for prompt relief of BPH symptoms (days)?
α1 receptor antagonists
Alfuzosin should not be given to tx BPH in patients with what impairment?
Hepatic impairment
What are the two steroid 5α-reductase inhibitors used for BPH?
How quickly do they work?
- Finasteride and Dutasteride
- Delayed action –> shrinkage and sx relief in 3-6 months
What are the direct effects (MOA) of steroid 5α reductase inhibitors?
- Directly inhibit production of DHT in prostate epithelial cells
- Cause TestosteroneaccumulationandDHT depletion
Which steroid 5α reductase inhibitor is specific for SAR-2?
Finasteride = SpeciFIc inhibitor of SAR-2
Which steroid 5α-reductase inhibitor is a dual inhibitor of both SAR-1 and 2?
Dunasteride = DUal inhibitor
Which steroid 5α-reductase (SAR) is most implicated in BPH and is seen in excess in a hyperplastic prostate?
SAR-2
Which steroid 5α-reductase inhibitor causes the greatest (90%) decrease in serum DHT?
Dutasteride
What are 4 AE’s associated with the steroid 5α-reductase inhibitors used for BPH?
- Erectile dysfunction
- Gynecomastia
- Depressed libido
- Ejaculation dysfunction
Caution should be taken when using 5α-reductase inhibitors in pts with what?
Liver abnormalities –> metabolized by hepatic CYP3A
Which PDE-5 inhibitor is now approved by the FDA to treat BPH as well as erectile dysfunction?
Tadalafil
Which PDE-5 inhibitor can be taken 15 mins prior (high dose) or 30 mins prior (normal dose) for ED?
Avanafil
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?
- Blue vision
- Blurred vision
What are 3 less common AE’s specific to tadalafil?
- Back pain
- Myalgia
- Limb pain
What is a major contraindication for PDE-5 inhibitors?
Why?
- Organic nitrates
- Extreme and dangerous hypotension
If using tadalafil for BPH, what should not be used at the same time?
Concurrent α1-blockers
Patients need to be what before starting vardenafil?
Hemodynamically stable
What are 2 second-line ED therapies?
- Vacuum erection devices
- Penile injections w/ alprostadil –> PGE 1 agonist
What is the MOA of Alprostadil?
- Leads to increases in cAMP
- Decreases in iCa2+
- Smooth muscle relaxation
- Erection
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?
- Prolonged erection (priapism)
- Medical emergency! Need to evacuate clogged blood
- Can result in permanent corporal fibrosis and ED
What is the pharmacological treatment for prolonged erection (priapism)?
Sympathomimetic (phenylephrine) + aspiration
What is recommended for using Sildenafil for ED and a concurrent α1-blocker for BPH?
Concurrent α-blockers initiated at lowest recommended dose
