Flashcards in Pharm of BPH and ED: Sweatman Deck (13)
Identify the various physiologic targets for BPH therapy and describe the respective mechanism of drug action
a-1 blockers---I a-1 receptors in bladder (a-1d), urethra, and prostate (a1-a)
(all end in -zosin)
Exception: a1-a selective blockers end in -osin
PDE-5 inhibitors (only tadalafil used for BPH):
---I PDE-5 which would normally convert cGMP---> GMP. cGMP is produced via the NO pathway, and acts to phosphorylate things that eventually leads to Ca++ efflux and SM relaxation---> vasodilation---> erection and relief of BPH symptoms.
5-alpha reductase inhibitors (-steride)
5-a-reductase converts testosterone---> DHT in prostate.
By inhibiting that conversion, you reduce DHT proliferation of the prostate---I BPH
Broadly characterize the principal route of metabolism/elimination for BPH drugs
Hepatic metabolism, fecal/renal elimination
Contrast the pattern of adverse effects for alpha-1a antagonists with that of the remaining alpha-1 drugs and recall the purported mechanism
All: AEs: dry mouth, nausea, dizziness, somnolence, asthenia, h/a, insomnia.
Advantage of selective a1-a (-osins): no need for dose titration (diminished effect on CV fxn)
AEs of a1-a: retrograde ejaculation, dopamine blockade.
Compare and contrast the specificity and adverse effects of the listed 5-alpha reductase inhibitors
Finasteride: type II 5-a reductase (urogenital tissue/genital skin)
Dutasteride: type I 5-a reductase (non-genital skin, liver, bone)
Both well tolerated.
Low incidence of ejaculatory dysfxn, ED, v libido, gynecomastia (all due do inhibition of DHT needed for these fxns)
Contrast current understanding regarding beta-sitosterol and saw palmetto effects upon BPH and, therefore, clinical utility
beta-sitosterol: symptomatic relief of BPH, w/o actually shrinking prostate
Saw palmetto- not enough evidence to support use. No more effective than placebo.
Contrast the delivery of alprostadil with the remaining drugs
Administered via urethral suppository or intracavernosal injection.
Localized action, minimal systematization.
Describe the respective mechanisms of drug action for treating ED.
PDE-5 inhibitors (-afil)---I PDE5 which would normally degrade cGMP---GMP. This allows for prolonged NO action---> SM dilation---> erection
PGE-1 mimic (Alprostadil) ---> activation of adenylyl cyclase ---> cAMP---> v intracellular Ca++---> SM relaxation---> erection
Contrast the adverse effects of alprostadil with the common and serious effects produced by PDE-5 inhibitors
AEs of alprostadil- penile, urethral, testicular pain and rarely CV effects.
AEs of the -afils (PDE-5 I's) are more systemic in nature. Headache and indigestion are most common. Rare but severe: ischemic optic neuropathy and sudden hearing loss.
Recall drugs absolutely contraindicated with PDE-5 inhibitors
NITRATES! ---> too much vasodilation ---> life threatening hypotension
Identify the PDE-5 inhibitor most likely to elicit QT prolongation with concurrent mediations
Describe the utility of testosterone supplementation
65% of hypogonadal men have an improvement in erectile function with testo supplementation.
Testo tx may also improve response to PDE-5 inhibitors.
Discuss the principal adverse effects of yohimbine and the role of this drug, given the equivocal response data
Easily crosses BBB. Can result in:
anxiety, antidiuresis, dizziness, flushing, h/a, HTN, incr. motor activity, irritability, nervousness/restlessness, sinus tachycardia, tremor.
MOAI action at supraclinical doses.
No clinical usefulness