GU Flashcards
All anti-spasmodics may cause confusion.* What does the CNS effects of antimuscarinics depend on?
CNS penetration PLUS M1 receptor binding
Where are M3 receptors and what is the effect of blocking them?
Bladder smooth muscle, salivary gland, eye, gut
AAG = DEC bowel/bladder contractility, dry eyes/mouth, and blurred vision
What are the 3 nonselective muscarinic AAG? What are common themes for their ADRs?
- tolterodine
- fesoterodine
- trospium
ADRs: xerostomia, constipation, fatigue/dizziness
What are the two ‘primarily’ M3 selective AAGs? Common theme of ADRs?
- oxybutynin
- solifenacin
ADRs: xerostomia, constipation
What is the M3 selective AAG?
- darifenacin
What is the MOA of nonselective muscarinic agents?
AAG M2 and M3 receptors on detrusor smooth muscle
INC bladder capacity, DEC uninhibited contractions, delay desire to void –> DEC IVS
Caution: pt w/urinary retention and closed angle glaucoma**
What are the CYP isoenzymes related to Tolterodine and Fesoterodine?
2D6 and 3A4 substrate
Tolterodine - QT issues
Why do we avoid using Oxybutynin?
Xerostomia
- rarely used bc of this intolerance**
What is the MOA of oxybutynin and solifenacin?
AAG primarily M3 receptor –> INC bladder capacity, DEC uninhibited contractions, delay desire to void –> DEC IVS
What must you remember about an elderly patient on a urinary antimuscarinic?
All products are on Beers List
What is Mirabegron used for and what is the MOA? What is the most concerning ADR?
OAB
MOA: B3 agonist
- relax bladder and INC storage capacity
ADR: HTN*
What drug interactions should you be aware of with Mirabegron?
Inhibits 2D6 and digoxin excretion
Tell me about the three different alpha receptors (r/t BPH) - location and results of AAG.
a1A
- prostate, bladder neck
- AAG = bladder neck / prostate relaxation
a1B
- peripheral vasculature
- AAG = orthostasis, syncope
a1D
- SC, bladder, nasal passages
- AAG = may help BPH sxs?
What two drugs are ‘a-blockers’ and what are the two MOA?
“-zosins”: terazosin, doxazosin
MOA:
- AAG a1A in bladder neck, prostate, urethra = relax smooth muscle = relieve OVS
- AAG a1B in vascular smooth muscle = relax vascular tone = postural hypotension / syncope (limited by dose titration*)
What are three clinical indications for a-blockers?
- BPH - not used d/t uroselective agents
- HTN - minimal use except “endocrine” HTN
- medical expulsive therapy for nephrolithiasis
What is the main C.I. with alpha blockers? What are two other interactions?
** C.I. with vasodilators - overlapping vasodilation**
- additive hypotension w/other anti-HTN
- avoid decongestants - may lead to acute urinary retention
5 ADRs related to alpha blockers?
- postural hypotension / dizziness *
- retrograde ejaculation *
- floppy iris syndrome
- drowsiness, fatigue
- nasal congestion / rhinitis
What are the three “uroselective” a-blockers? And MOA?
- alfuzosin
- tamsulosin
- silodosin
MOA: a1A AAG = smooth muscle relaxation
What is a clinical pearl regarding tamsulosin?
Nonsulfonylarylamine
What are the clinical indications for uroselective a-blockers?
Men: BPH
Women: improve sxs d/t bladder outlet obstruction (not FDA approved)
Both: off-label to pass kidney stones
What ADRs are r/t uroselective a-blockers?
- less postural hypotension / dizziness
- more retrograde ejaculation (silodosin»_space; tamsulosin > alfuzosin)
- floppy iris syndrome (MC w/tamsulosin)
- QT issues (alfuzosin)
What two drugs work as 5a-reductase inhibitors?
- finasteride
- dutasteride
Inhibits conversion of testosterone to dehydrotestosterone
What are the clinical pearls with 5a-reductase inhibitors?
- shrinks prostate
- 6-12 mo for max effect
- may use w/a-blockers
** DEC [PSA] ~ 50% –> dec overall risk of prostate cancer
What are the clinical indications of 5a-reductase inhibitors?
- both agents = BPH
- Finasteride = male-pattern baldness
What is the precaution regarding 5a-reductase inhibitors?
- preg women should not handle (can be absorbed through skin)
** abnormalities of external male genitalia reported (cat X)
What are two ADRs related to 5a-reductase inhibitors?
- ED and ejaculation disturbances
2. Rare reports of high-grade prostate CA (both) and male breast cancer (finasteride)
What other condition should pop into your mind with an ED patient?
CAD
** ED is a “vascular equivalent” - occurs 2-5yrs before CAD [potential window to create lifestyle changes to prevent CAD] **
Describe the general treatment plan for ED?
- Lifestyle
- PDE5 inhibitors
- Intraurethral or intracavernosal alprostadil
- Implant or vacuum device
What is the MOA of PDE5 inhibitors? What are some examples of these meds?
Inhibits PDE5 to prevent breakdown of cGMP –> potentiates relaxation of smooth muscle –> engorgement
Avanafil, Sildenafil, Vardenafil, Tadalafil
What are the 3 main clinical indications for PDE5i?
- ED
- all PRN, Tadalafil approved for daily use to inc spontaneity - BPH
- Tadalafil - consider if BPH & ED - Pulmonary Arterial* HTN
- Sildenafil, Tadalafil
What drug is C.I. in someone on a PDE5i?
Nitrates** - catastrophic hypotension possible
What are the class ADRs related to PDE5i?
- VD = HA, facial flushing, nasal congestion, dyspepsia
- Priapism*
- Nonarteric ischemic optic neuropathy
- blood flow blocked to optic nerve = sudden vision loss
What are two unique ADRs with PDE5i?
- Sildenafil - cyanopsia
2. Tadalafil - backache and myalgias
What are the clinical indications for Flibanserin?
Tx PREmenopausal women w/FSIAD (female sexual interest / arousal disorder) not caused by another medical/psych condition
What are the clinical pearls regarding Flibanserin?
- not approved for men or POSTmenopausal women*
- may take 8wk for max effect*
- dose at night to dec r/o hypotension, syncope, CNS depression
Describe the Pk of Flibanserin?
2C19 and 3A4 substrate
- mod/strong inhibitors C.I.
- single dose of fluconazole for vaginitis is Bad!**
Pgp inhibitor
Flibanserin is on the REMS program. What must the prescribe counsel patient on and why?
** Must counsel patient on risk of alcohol consumption **
EtOH C.I. d/t severe hypotension and syncope
Besides Flibanserin, what is the other medication indicated for PREmenopausal FSIAD?
Bremelanotide
- SQ injection 45min before anticipated sex
What is the main drug interaction to be aware of with Bremelanotide?
May slow gastric emptying and alter rate of absorption of PO drugs
Be thoughtful with GLP-1s, opioids, lubiprostone
Who is Bremelanotide C.I. in?
Women with CVD or uncontrolled HTN
Transient INC BP and DEC HR after each dose
List some ADRs related to Bremelanotide?
- Nausea (esp w/first dose)
- flushing
- injection-site rxn
- HA
- hyperpigmentation* rare, but may not be reversible
