Flashcards in Pharm of Overactive Bladder: Sweatman Deck (8)
Describe neuronal connections to the urinary bladder, including receptor sub-types, and explain the storage and voiding reflexes.
PSNS---> ACh---> M3 muscarinic receptors on bladder--> bladder contraction ---> voluntary micturition "urination"
PSNS---> ATP (excites bladder SM) + NO (relaxes urethral SM)---> voluntary micturition
SNS---> norepinephrine (NE) ---> B3 adrenergic receptors ---> relaxes bladder SM (no micturition)
SNS---> NE ---> a1 adrenergic receptors---> urethral SM contraction (no micturition)
Somatic NS--> ACh ---> contraction of external urethral sphincter striated muscle (no micturition)
SNS: B3- detrusor relaxation
M2 in bladder- opposes B3 (SNS effect)
M3 in bladder- direct effect to increase contraction of detrusor
Recall the types of incontinence for which antimuscarinics and alpha-agonists are indicated and the rationale for cholinomimetic drugs.
Indicated for urge (detrusor over-activity) - antimuscarinics (relaxation of detrusor)
Outlet incompetence- a-agonists (contraction of urethral SM)
Rationale for cholinomimetics:
Bethanechol and neostigmine are given to treat bladder tone insufficiency (can't empty bladder).
Also used to treat opiate induced bladder insufficiency.
Beth- muscarinic agonist
Neo- AChEsterase antagonist
Comparatively evaluate the mechanism of action, central vs. peripheral actions and the adverse effects of the alpha-agonists and anticholinergic drugs.
MOA of a- agonists ---> urethral SM contraction ---I urine flow
MOA of anticholinergics---I M2/M3 PSNS activity ---I bladder contraction
Peripheral effects: (all anti PSNS effects) dry mouth, myadriasis, constipation, urinary retention, tachycardia
Sedation, confusion/delirium, hallucinations, slowed cognitive fxn, sleep disruption. (can't relax)
Explain the contraindications to use of antimuscarinic drugs in the setting of overactive bladder.
Glaucoma, Urinary/GI obstruction (gotta get that shit moving), need for mental alertness, Alzheimer's type dementia (worsen existing cholinergic deficit)
Describe the patient profile most likely to respond to botox to treat overactive bladder.
Pts who responded to anticholinergic drugs but could not tolerate the AEs. Botox injected into the urothelial wall.
Botox MOA: inhibits vesicular release of excitatory neurotransmitters thought to cause detrusor overactivity.
Discuss the clinical utility of methionine and collagen injection for treatment of overactive bladder.
Methionine reduces odor associated with leaked urine. (ancillary effect) - creates ammonia-free urine by acidifying pH
Collagen injections "bulk up" the tissues at the sphincters and urethra to help w/ incontinence by creating a mass effect to block flow.
Explain opiate-induced urinary retention and how it is treated.
Mediated by mu and delta receptors in sacral cord inhibiting PSNS outflow ---I detrusor activation.