Muscarinic Agonists and Antagonists Flashcards
What G protein receptor is used for M1, M2, and M3?
M1 and M3 - Gq
M2 - Gi
What is the postreceptor mechanism of Gq?
Phospholipase C, IP3, DAG mediated cascade, causes intracellular release of calcium
= muscle contraction
What is the postreceptor mechanism of Gi?
Blocks adenylylcyclase, causing inhibition of cAMP production and activation of K+ channels
= prevention of muscle relaxation
What drugs are muscarinic agonists?
Carbamylcholine (carbachol)
Acetyl-beta-methylcholine (methacholine)
Bethanechol
Pilocarpine
Which muscarinic agonist is not resistant to hydrolysis by AChE?
Acetyl-beta-methylcholine (methacholine)
Slowly hydrolyzed by AChE
Which muscarinic agonists are selective for specific muscarinic receptors?
None! No selective agonists
Which muscarinic agonist is more selective for nicotinic receptors than muscarinic?
Carbamylcholine (carbachol)
Which muscarinic agonist has best potency at M2 receptors (cardiac)?
Acetyl-beta-methylcholine (methacholine)
Which muscarinic agonist has no selectivity for nicotinic receptors?
Bethanechol
Which muscarinic agonist can penetrate the BBB and membranes?
Pilocarpine
What are symptoms of parasympathetic overstimulation?
DUMBBELSS Diarrhea Urination Miosis Bronchoconstriction Bradycardia Emesis Lacrimation Salivation Sweating
What are the clinical uses of carbamylcholine (carbachol)?
Glaucoma (constriction of sphincter and drainage of fluid)
What are the clinical uses of acetyl-beta-methylcholine (methacholine)?
When inhaled, causes bronchoconstriction (challenge test for asthma diagnosis)
What are the clinical uses of bethanechol?
GI disorders: postoperative ileus, congenital megacolon, GERD
Urinary retention
What are the clinical uses of pilocarpine?
Glaucoma (constriction of sphincter and drainage of fluid)
Xerostomia (dry mouth)
What are the clinical uses of miochol (just is drug name for ACh)?
Cataract extraction
What are contraindications to the use of muscarinic agonists?
Asthma - don’t want to bronchoconstrict
Hyperthyroidism - tendency for atrial fibrillation, don’t want to affect heart pacing
Coronary insufficiency - bradycardia, reduced cardiac output, reduced blood flow through coronary vessels
Peptic ulcer - activation of M1 receptors increases gastric secretion
Mechanical obstruction of GI tract - gastric motility contraindicated
What drugs are muscarinic antagonists?
Atropine Scopolamine Tropicamide Glycopyrrolate Cyclopentolate Pirenzepine Tiotropium, Ipatropium Tolterodine, Darifenacin
Which muscarinic antagonists are non-selective?
Atropine Scopolamine Tropicamide Glycopyrrolate Cyclopentolate
Which muscarinic antagonists are highly selective for M1?
Pirenzepine
Tiotropium, Ipatropium
Which muscarinic antagonists are highly selective for M3?
Tiotropium, Ipatropium
Tolterodine
Darifenacin
What are symptoms of blockade of parasympathetic stimulation?
Blocks DUMBBELSS, causing: Reduced GI motility Urinary retention Mydriasis Bronchodilation Tachycardia Lack of emesis Decreased lacrimation (dry eye) Decreased sweat (dry skin) Decreased salivation (dry mouth)
What muscarinic antagonists are used to treat respiratory illnesses like cold and chronic bronchitis and emphysema?
Tiotropium, Ipatropium
Opens bronchi, reduce secretions, but no effect on sputum viscosity
What muscarinic antagonists are used to treat GI hypermotility?
Glycopyrrolate
What muscarinic antagonists are used to treat stomach ulcers?
Pirenzepine
What muscarinic antagonists are used to treat overactive bladder?
Darifenacin, Tolterodine
M3 selective; have higher selectivity for M3 in detrussor muscle than in salivary glands
What muscarinic antagonists are used Pre-anesthesia (to inhibit salivation and respiratory secretions to put in endotracheal tube)?
Atropine
Glycopyrrolate
What muscarinic antagonists are used Post-anesthesia (prevent muscarinic activation by AChE inhibitor given to counteract muscle relaxant given earlier)?
Atropine
Glycopyrrolate
Scopolamine also used post anesthesia but used because at high doses it may tranquilize and produce amnesia following surgery
What muscarinic antagonists are used to cause mydriasis for eye examination?
Tropicamide
Cyclopentolate
What muscarinic antagonists are used to treat motion sickness?
Scopolamine
Transdermal patch behind ear allows diffusion of scopolamine to M1 receptors in inner ear
What are contraindications to the use of muscarinic antagonists?
Narrow-angle glaucoma - dilated iris blocks exit of aqueous humor through trabeculum
Cardiac arrhythmia - similar to muscarinic agonists, do not want to disrupt heart rhythm
Chronic lung disease - via drying effect
What is a common cause of muscarine poisoning?
Mushrooms, specifically Inocybe, Clitocybe, Amanita muscaria
What is the treatment for muscarine poisoning?
Atropine
