Muscarinic Antagonists Flashcards
Muscarinic Receptors: Antimuscarinic receptor
acts at the postganglionic neuroeffector junction to block parasympathetic autonomic discharge
Nicotinic Receptors: Neuromuscular Block
act at the neuromuscular junction to block AcH signaling
Nicotinic Receptors: Ganglionic Blockers
act as antagonists at both parasympathetic and sympathetic autonomic ganglia
M1, M3, M5 action
signal via intracellular Ca2+ increase and PKC activity
M1(Galphaq) site
CNS, sympathetic postganglionic and presynaptic sites
M3(Galpha) site:
smooth muscle, lungs, eyes effector cell membranes
M2, M4 action
signal via cAMP decrease and reduced cAMP-dependent PK activity
M2(Galphai) site:
located in myocardium, smooth muscle, and presynaptic sites(K+ channel linked = slow heart rate)
M4(Galphai) site:
located in the CNS
Atropine description
- muscarinic antagonist isolated from aorta belladonna
- increased pupil size
Ocular exams and antimuscarinic drug
Mydyriasis: pupil dilation; inhibit Ach action on M3 receptor in pupillary constrictor muscle.
Cycloplegia: loss of focus/regulation of lens thickness; inhibit Ach action on M3 receptor in ciliary muscle
Incontinence and antimuscarinic drug
- Bladder relaxation via M3 receptor which mediates contraction of the bladder
- M2 receptor(indirectly) inhibits relaxation
IBS and antimuscarinic drug
- induce GI tract intestinal paralysis(antispasmodic agents)
- reduce secretions
- Mebeverine
COPD and antimuscarinic drugs
- reduce secretions, cause bronchial dilation
- in combination with a Beta-adrenergic agonist
Preoperative antisecretory and antimuscarinic drugs
- used with inhalant anesthetics to reduce accumulations of secretions(salivary, mucous membranes of rest. tract)
Two other uses for antimuscarinic drugs
- motion sickness
- parkinson disease; as an adjunct to L-DOPA
Mechanisms of antimuscarinic drugs
- competitive and reversible inhibition of muscarinic receptor activation by preventing binding of Ach
- two general classes based on their structure
Tertiary amines of antimuscarinic drugs
- mainly used in ocular and CNS applications
Quaternary amines/ammonium of antimuscarinic drugs
- mainly used in GI tract and peripheral applications
Long lasting tertiary amines
- atropine and scopolamine
Description of long lasting tertiary amines
- nonselective antagonists
- tertiary compounds can penetrate CNS
Scopolamine description
- naturally occurring
- CNS penetration better than atropine
- drowsiness(low doses) or hallucinations(high doses)
- side effects include confusion, dilated pupils, tachycardia
Scopolamine uses
- motion sickness
- reduce nausea
Side effects of scopolamine
- amnesia
Administration of Scopolamine
- patch
- 1.5mg patch will deliver 1mg over 3days transdermally
Scopolamine not recommended for
- for children or the elderly due to toxicity
Withdrawal from scopolamine
- receptor sites are sensitized over time
- cholinergic neurotransmitters are accumulated
- rebound effects when scopolamine is stopped, causing overstimulation of vestibular nuclei and reticular formation
Symptoms of withdrawal from scopolamine
nausea
headache
blurred vision
Treatment options for withdrawal of scopolamine
- bonine(mezcline) is antihistamine
- dramamine
Shortacting tertiary amines
Tropicamide(0.25day)
Homatropine(1-3day)
Effect of tropicamide
used in optical applications
causes cycloplegia and mydriasis
shorter duration than atropine
Cycloplegia description
paralysis of the ciliary muscle of the eye, resulting in loss of accommodation
Muscarinic antagonists commonly used for
dilation of pupil for eye exams
Types of urinary incontinence
stress
urge
outflow
functional
Stress incontinence description
laxity of pelvic floor muscle
leak with cough or laughing
history of vaginal childbirth
treat with adrenergic agonist
Urge incontinence description
increased detrusor muscle activity(overactive bladder)
nocturia, small volume, increased frequency
treat with anticholinergics
Outflow incontinence description
urinary retention secondary to obstruction or bladder anatomy
nocturia, small volume, increased frequency
treat with cholinergics(atony), alpha antagonists(obs.)
Functional incontinence description
due to large volume intake
Diabetes effect on incontinence
- overweight and pressure on bladder
- diabetic neuropathy
1. diabetic bladder dysfunction: overactive bladder: urge- diabetic cystopathy: decreased bladder sensation, increased capacity: outflow
- gestational diabetes; increased baby weight; damage to bladder sphincter
- CHF; retain water; create too much urine at night; nocturia
- constipation common in diabetes
- leftover urine can cause UTI; increase urge and frequency
Muscarinic antagonist for urinary incontinence; tertiary amines
suppress involuntary bladder contraction
increase maximal urine volume
M3 selective for urinary incontinence
Darifenacin, Solifenacin
longer acting than oxybutinin
M2/M3 selective for urinary incontinence
Tolterodine
fewer side effects than oxybutinin
M1/M3 selective for urinary incontinence
Oxybutinin
ER or patch with dry mouth side effect
Quarternary amines used for GI disorders
Probanthine
used to treat gastric disorders(GI spasm, peptic ulcers)
charged N makes crossing gut difficult
peripherally restricted
Antispasmotics for IBS
Atropine - Saltropine
Dicyclomine - Bentyl
Hyoscyamine - Levsin
Contraindications for antispasmotics
glaucoma
long term/continuous use
M3 receptors and bronchial smooth muscle action
M3 receptors mediate constriction of bronchial smooth muscle.
M3 antigonist function on bronchial smooth muscle
block Ach-mediated constriction and open the airways
M3 antagonist and COPD
- used as inhalant drug for COPD, asthma
- less effective as a mono therapy, but enhances the therapeutic effect of beta-adrenergic agonists in COPD
Ipratropium description
- short acting, rescue inhaler
Tiotropium description
- long acting, daily inhaler
Tertiary amines used for Parkinson’s disease
- action through CNS M1 receptor
- used as an adjunct therapy with LDOPA in PD patients
- improve balance between dopaminergic and cholinergic neurotransmission
- disruption of Ache => increase Ach, decrease DA
- treat extrapyramidal side effects of antipsychotics
Antipsychotics drugs with anticholinergic activity
chlorpromazine - thorazine clozapine - Clozaril mesoridazine - serentil olanzapine - zyprexa promazine - sparine quetiapine - seroquel thioridazine - mellaril
Tricyclic antidepressants with anticholinergic activity
amitriptyline - elavil desipramine - norpramin doxepin - sinequan imipramine - tofranil nortriptyline - aventyl, pamelor
Antiarrythmics with anticholinergic activity
discopyramide - norpace
procainamide - pronestyl
quinidine - quinaglute, quinidex
Antihistamine with anticholinergic activity
azatadine - optimine
chlorpheniramine - chlortrimeton
clemastine - tavist
diphenydramine - tylenol, sominex, benadryl
Contraindications for antimuscarinic drugs
- open/narrow angle glaucoma
- tachycardia; increase HR
- ileus obstruction
- urinary obstruction
