Describe the localization of a1 receptors in the male urinary tract
Alpha 1a receptors predominate in the lower GU tract (trigone of the bladder, prostatic urethra and prostate gland), whereas alpha 1d receptors are more common in the destrussor muscle of the urinary bladder
What are some a1-blockers?
Przocin, Alfuzosin, Terazocin, Doxazocin, Tamsulosin, Silodosin
How are a1 blockers given? DOA?
Orally (CYP interactions). The DOA of most of these drugs is long except prazosin, which shows variability among pts. and most be titrated
What are some common AEs of a1-blockers?
orthostatic hypotension and syncope
Xerostomia, dizziness, HA, nausea
Which a1 blockers are selective against a1a receptors? AEs?
Tamsulosin and Silodosin (AEs include diminished effects on CV function, dopamine blockage, and increased sexual (reverse ejaculation) dysfunction)
All a1 blockers have comparable efficacy. What are some advantages and disadvanatages of a1a blockers?
advantages- no need for dose titration
disad.- abnormal ejaculation (more with silodosin)
What is the generally accepted best a1 blocker for BPH?
alfuzosin (has very little side effects)
How does NO act at a molecular level?
cGMP mechanisms leading to influx of Ca2+ and smooth muscle relaxation, vasodilation of the penial arteries and erection
How do PDE5 inhibitors work?
they prevent breakdown of cGMP by pDE5, rsulting in prolonged erection
What are some PDE5 inhibitors?
Tadalafil (Cialis)- only one for BPH tx
Avanafil, Sildenafil, Vardenafil
What are some AEs of Tadalafil?
HA, nausea, nasopharyngitis, URTIs
non-arteritic ischemic optic neuropathy, retinal artery occlusion, hearing loss
What does the enzyme 5a-reductase do?
converts testosterone to DHT
What are the types of 5a-reductase?
Type I: mostly found in non-genital skin, liver, and bone
Type II: mostly found in urogenital tissue and genital skin
What are the 5a-reductase inhibitors?
Finasteride (type I) and Dutasteride (type I and II)
Describe 5a-reductase inhibitors
They are competitive binders that bind for a long time and are metabolzied hepatically
AEs of 5a-reductase inhibitors?
-category X preg
-low incidence of AEs but can get ejaculation and erectile dysfunction, decreased libido, and gynecomastia
Also decreases PSA levels (caution in a pt. with prostate cancer)
What are Beta-sitosterols?
Natural products that have been shown to improve urinary symptom scores and flow measures but did not significantly reduce prostate size
What is Saw palmetto?
Natural product for BPH- no evidence it's effective- DONT recommend
Drugs for erectile dysfunction
What is Alprostadil?
A drug that mimics PGE1. It works by activating adenylate cyclase, which synthesizes cAMP from ATP to promote smooth muscle relaxation and erection
Very few AEs due to localized injection in the penis
How is Alprostadil given?
Either intra-urethral suppository palced to dissolve in residual urine and then absorbed across the urethral wall or via direct injection into the corpus cavernosum
What are the benefits of local placement of Alprostadil?
Minimal systemization, rapid onset (minutes), and a lasting effect for hrs.
AEs of Alprostadil?
penile (36%), urethral (13%), and testicular (5%) pain
rare CV effects
DD interactions with PDE5 inhibitors?
contraindicated with nitrates
caution with alpha blockers (increased hypotension), and other 3A4 drugs
Other AEs of PDE5 inhibitors?
Well tolerated but naopharyngitis, URTIs, vision and hearing loss
vardenafil has a risk of QT prolongation
Note that the hormonal supplementation of testosterone has been shown to improve erectile dysfunction in hypogonadal men and may improve the response to PDE5 inhibitors
What is Yohimibine?
An alpha-2 receptor inhibitor that appears to involve blockade of post-synaptic adrenergic receptors and stimulating pre-synaptic hetero-receptors on NANC nerves to cause vasodilation
AEs of Yohimibine?
-not all that effective
-crosses BBB potentially producting anxiety, antidiuresis, dizziness, HTN, etc.
MAOI action at high dose (tyramine and caffeine interactions possible)
-worsens renal function
Note that many many drugs list ED as a potential AE so keep that in mind during evaluation