Muscarinic Antagonists Flashcards
Antimuscarinic
acts at the post-ganglionic neuroeffector junction to block parasympathetic autonomic discharge
Neuromuscular blocker
acts at the neuromuscular junction to block acetylcholine signaling
Ganglionic blockers
act as antagonists at both parasympathetic and sympathetic autonomic ganglia
M1, M3 and M5 receptors signal via
intracellular Ca2+ increase and PKC activity
M2 and M4 receptors signal via
cAMP decrease and reduced cAMP-dependent PK activity
M1 (G alpha q) receptors are located where?
CNS, sympathetic postganglionic cells and presynaptic sites
M3 (G alpha q) receptors are located where?
smooth muscle, lungs, eyes, effector cell membranes
M2 (G alpha I) receptors are located where?
myocardium, smooth muscle, and presynaptic sites (K+ channel linked = slow heart rate)
M4 (G alpha I) receptors are located where?
in the CNS
Atropa belladonna
deadly nightshade
Primary clinical uses for antimuscarinic drugs
ocular exams, incontinence, irritable bowel syndrome
Secondary clinical uses for antimuscarinic drugs
COPD, pre-operative anti-secretory, motion sickness, Parkinson’s disease
Antimuscarinic drug use in ocular exams
mydyriasis (pupil dilation): inhibits Ach action on M3 receptors in pupillar constrictor muscles
cycloplegia (loss of focus/lens thickness): inhibits Ach action of M3 receptors in the ciliary muscles
Antimuscarinic drug use for incontinence
bladder relaxation: inhibits M3 receptors (mediate contraction of the bladder) and M2 receptors (which inhibit relaxation)
Antimuscarinic drug use for irritable bowel syndrome
induces GI tract intestinal paralysis and reduces secretions
Mebeverine
antimuscarinic drug used for IBS
Antimuscarinic drug use in COPD
reduces secretions, causes bronchial dilation in combination with a beta-adrenergic agonist
Antimuscarinic drug use pre-operative (anti-secretory)
used with inhalant anesthetics to reduce accumulations of secretions (salivary, mucous membranes of respiratory tract)
Long lasting tertiary amines
atropine and scopolamine
Atropine and Scopolamine are used to treat
GI/urinary conditions, COPD, motion sickness, adjuct for Parkinson’s
Side effets of Scopolamine
drowsiness (low dose) or hallucinations (high doses)
confusion, dilated pupils, tachycardia
can cause amnesia
What happens when scopolamine treatment is stopped suddenly
rebound effects - causing an overstimulation of the vesitubular nuclei and the reticular formation of the vomiting center (nausea, headache, and blurred vision)
Scopolamine can be specifically used for
motion sickness and reducing nausea (scopolamine patch)
How can the withdrawal symptoms of scopolamine be alleviated
using anti-histamines or leaving the scopolamine patch on for a longer time to “squeeze out” the last bit of scopolamine over a prolonged time
Tropicamide is primarily used for
eye exams
What does tropicamide cause
cycloplegia and mydriasis
Why would you want to dilate the pupil when evaluating a patient with glaucoma?
a dilated pupil enables examination of the terminal ends of the optical nerve and the nerves at the terminus are thinner and the first to be damaged by glaucoma
Types of urinary incontinence
Stress incontinence, urge incontinence, outflow incontinence, functional incontinence
Stress incontinence
laxity of pelvic floor muscle, leaks with cough or laughing, history of vaginal childbirth
Treat stress incontinence with
adrenergic agonists
Urge incontinence
increased detrusor muscle activity (overactive bladder), nocturia, small volume, increased frequency
Treat urge incontinence with
anti-cholinergics
Outflow incontinence
urinary retention secondary to obstruction or bladder atony, nocturia, small volume, increased frequency
Treat outflow incontinence with
cholinergics (atony) or alpha antagonists (obstruction)
Functional incontinence
due to large volume intake
How can gestational diabetes cause incontinence
gestational diabetes -> increased baby weight -> damage to bladder sphincter
How can congestive heart failure cause incontinence
CHF -> retain water -> create too much urine at night -> nocturia
How are muscarinic antagonists used to treat urinary incontinence
by relaxing the obtrusor muscle in the bladder and increasing maximal bladder volume
What kind of muscarinic receptors does the bladder contain?
both M2 and M3 receptors
Prolonged use of muscarinic antagonists for urinary incontinency may lead to
acute urinary retention
M3 selective muscarinic antagonists used for urinary incontinence
Darifenacin and Solifenacin
M2/M3 selective muscarinic antagonist used for urinary incontinence
Tolterodine
M1/M3 selective muscarinic antagonist used for urinary incontinence
Oxybutynin (dry mouth is a common side effect)
Probanthine
used to treat gastric disorders (GI spasms, peptic ulcers), peripherally restricted
Antispasmotics are used for?
irritable bowel syndrome
Name 3 antispasmotics
Atropine, Dicyclomine, Hyoscyamine
When should you avoid using antispasmotics?
avoid in glaucoma patients and avoid long term/continuous use
How do M3 antagonists work in COPD?
M3 receptors mediate constriction of bronchial smooth muscle so M3 antagonists will block Ach-mediated constriction and open the airways
muscarinic antagonists used for COPD
“-tropium”
Ipratropium, Tiotropium
Ipratropium
short acting, rescue inhaler for COPD
Tiotropium
long acting, daily inhaler for COPD
Muscarinic antagonists for the management of COPD and asthma are more effect when?
when co-administered with a beta2 blocker
Drug classes known to contain drugs with anti-cholinergic activity
anti-histamines, anti-psychotics, TCA’s and anti-arrythmics
Tricyclic anti-depressant choice for the elderly
Nortryptaline because it only has mild-moderate anti-cholinergic effects
Common contraindications for anti-muscarinic drugs
open/narrow angle glaucoma, tachycardia, ileus (intestinal obstruction), urinary obstruction (BPH)
