CH 16-17 Muscarinic Agonists & Antagonists Flashcards
Effect of muscarinic agonists on the urinary tract
Activation of muscarinic cholinergic receptors
* contraction of bladder detrusor
– increased pressure
* relaxation of the bladder trigone
* relaxation of the bladder sphincter
Result: bladder emptying
Overactive Bladder (OAB)
Definition
Also known as:
- urgency incontinence
- detrusor instability
OAB is a condition characterized by a sudden, uncontrollable urge to urinate that may lead to involuntary urine loss. It is a type of urinary urgency syndrome and is not caused by infections or other obvious pathology.
*It is more common in older adults but is not a normal part of aging.
- 40 years = 3-4%
- >75 years = 42% men, 31% women
Types of Overactive Bladder (OAB)
- Urgency - A sudden, strong need to urinate that is difficult to delay.
- Frequency - Urinating more often than usual, typically more than 8 times in 24 hours.
- Nocturia - Waking up more than once during the night to urinate.
- Urgency Incontinence - Involuntary loss of urine immediately following a strong urge to urinate (not always present in all cases of OAB).
General Tx of Overactive Bladder (OAB)
Tx: Treatment
First line: behavioral modification
- more frequent urination
- limiting fluid intake
Second line: pharmacotherapy
- only used if behavioral modification ineffective
- anticholinergics (class of choice)
Muscarinic receptor subtype M1
Location: salivary glands
Activation (↑): salivation
Blockade (↓): dry mouth
Location: CNS
Activation (↑): enhanced cognition
Blockade (↓): confusion, hallucinations
Muscarinic receptor subtype M2
Location: heart
Activation (↑): bradycardia
Blockade (↓): tachycardia
Muscarinic receptor subtype M3
Location: bladder detrusor
Activation (↑): contraction; improved emptying
Blockade (↓): relaxation; improved storage
———- others
Location: salivary glands
Activation (↑): salivation
Blockade (↓): dry mouth
Location: GI smooth muscle
Activation (↑): incr. tone & motility
Blockade (↓): dec. tone & motility; constipation
Location: eyes (iris sphincter)
Activation (↑): contraction; miosis
Blockade (↓): relaxation; mydriasis
Location: eyes (ciliary muscle)
Activation (↑): contraction; accommodation
Blockade (↓): relaxation; blurred vision
Location: eyes (lacrimal gland)
Activation (↑): tearing
Blockade (↓): dry eyes
Why is muscarinic receptor specificity important?
To decrease side effects
Drug: darifenacin (Enablex)
Class: Anticholinergic (Antimuscarinic) Agents
Tx: OAB
Parasympathetic drug:
Receptor antagonist (inhibits contraction)
- highly M3 selective
– minimal side effects - very expensive $$$
Drug: oxybutynin (Ditropan; Oxytrol)
Class: Anticholinergic (Antimuscarinic) Agents
Tx: OAB
Parasympathetic drug:
Receptor antagonist (inhibits contraction)
- primarily M3 selective
– minimal side effects - moderately expensive $$
Drug: solifenacin (VESIcare)
Class: Anticholinergic (Antimuscarinic) Agents
Tx: OAB
Parasympathetic drug:
Receptor antagonist (inhibits contraction)
- primarily M3 selective
– minimal side effects - moderately expensive $$
Drug: festerodine (Toviaz)
Class: Anticholinergic (Antimuscarinic) Agents
Tx: OAB
Parasympathetic drug:
Receptor antagonist (inhibits contraction)
- non-selective
– greater side effects - inexpensive $
Drug: tolterodine (Detrol; Detrol LA)
Class: Anticholinergic (Antimuscarinic) Agents
Tx: OAB
Parasympathetic drug:
Receptor antagonist (inhibits contraction)
- non-selective
– greater side effects - inexpensive $
Drug: trospium (Sanctura; Sanctura XR)
Class: Anticholinergic (Antimuscarinic) Agents
Tx: OAB
Parasympathetic drug:
Receptor antagonist (inhibits contraction)
- non-selective
– greater side effects - inexpensive $
Drug: mirabegron (Myrbetriq)
Class: Beta-3 Adrenergic Agonist
Tx: OAB
Sympathetic drug:
Receptor agonist (bladder relaxation; increased storage)
- selective for Beta-3
Drug: vibegron (Gemtesa)
Class: Beta-3 Adrenergic Agonist
Tx: OAB
Sympathetic drug:
Receptor agonist (bladder relaxation; increased storage)
- selective for Beta-3
Anticholinergic (muscarinic blocker) AE & DI
AE: Adverse Effects; DI: Drug Interactions
AE: (typically dose-dependent)
- dry mouth
- blurred vision
- photophobia
- tachycardia
- urinary retention
- constipation
- anhidrosis
Use cautiously or not at all with:
- antihistamines
- tricyclic antidepressants
- phenothiazine antipsychotics
Anticholinergic (Antimuscarinic) Preparations
- PO (immediate release)
- PO (delayed release)
- Transdermal path
- Topical gel
Muscarinic Agonist overdose symptoms
SLUDGE & the Killer Bees
S - salivation
L - lacrimation
U - urination
D - diaphoresis/diarrhea
G - GI cramping
E - emesis
B - bronchospasm
B - bronchorrhea
B - blurred vision
B - bradycardia or tachycardia
Also, hypotension, confusion, & shock
Drug: bethanechol (Urecholine)
Class: Cholinergic agonist (direct-acting)
Tx: urinary retention, adynamic ilius (↑ intestinal motility), gastric atony (↑ gastric motility & smooth muscle contraction)
Admin: 1hr before/2hr after meals
Muscarinic Agonist CI
CI: Contraindication
risk of perforation or rupture
- peptic ulcer disease
- urinary tract obstruction
- intestinal tract obstruction
risk of additional parasympathetic stimulation
- hypotension (severe hypotension)
- asthma (bronchospasm, bronchorrhea)
- coronary insufficiency (brady/tachycardia)
- hyperthyroidism
