ANS - Cholinergic Pharmacology I Flashcards
Are there muscarinic receptors in the brain?
Yes, M5 and M1 (M1 will be discussed in GNE part of enteric system as well)
What are the multiple locations of muscarinic recptors?
CNS, and receptors of parasympathetic postganglia
What do muscarinic agonists activate?
Muscarinic agonists will activate everything the parasympathetics would do regardless if it’s an appropriate response
What was the first identified agonist of muscarinic receptors?
Muscarine - from mushrooms (mimicry)
Why would the skin be effected by exogenous acetylcholine?
There are muscarinic receptors on a lot of blood vessels regardless whether there is parasympathetic nerves their or not, mismatch between parasympathetic and sympathetic
What are organ system effects of acetylcholine?
Same as parasympathetic response
Why does acetylcholine itself have virtually no therapeutic applications?
Acetylcholine has virtually no therapeutic applications because its actions are diffuse (activates everything) and because its hyrolysis (acetylcholinesterase, plasma butyrylcholineesterase) is rapid.
Why are bethanechol and pilocarpine therapeutically-useful muscarinic agonists?
Resistant to cholinesterases, limited (or no) nicotinic activity, retain activty at relevant organ systems
Carbachol
Muscarinic/Nicotinic Agonist, Clinical Applicatiion - Glaucoma, open-angle, Adverse Effects - Sweating, shivering, nausea, dizziness, increased frequency of urination, rhinitis (oral formulation), Contraindications - Acute iritis or glaucoma after cataract extraction, Narrow-angle (angle-closure) glaucoma, Considerations - Enhanced nicotinic action relative to other choline esters, cannot be use systemically b/c of unpredictable action at autonomic ganglia, topical applciaton of carbachol to teh cornea of the eye results in both pupillary constriction (miosis) and decreased intraoccular pressure
Bethanechol
Muscarinic Agonist - longer acting, Clinical Application - post operative abdominal distention (oral), gastric atony (oral), non-obstructive urinary retention (sub cutaneous), Adverse effects - Sweating, shivering, nausea, dizziness, increased frequency of urination, rhinitis (oral formulations), Contraindication - obstructive urinary retention, Considerations - Resistant to Acetylcholinesterase, no nicotinic activity
Pilocarpine
Muscarinic Agonist, Clinical Application - Xerostomia ‘dry mouth’ (oral) - Sjorgen syndrome or radiation to head and neck, initial treatment of glaucoma both open angle and closed angle (instilled in eye), potent stimulator of sweat, tear, saliva Considerations - resistant to Acetylcholinesterase, can cross blood brain barrier - tertiary amine
Methocholine
Muscarinic Agonist - short acting, Clinical Application - Stimulates muscarinic receptors in airway when inhaled, diagnosis of asthma, Adverse effects - Dyspnea, lightheadness, headache, pruritus, throat, irritation Contraindications - recent heart attack or stroke , aortic aneurysm, uncontrolled hypertension, Considerations - Methacholine is highly resistant to acetylcholineesterase but retains some susceptibility (this exploited for challenge test for astham diagnosis), relatively selective for cardiovascular muscarinic cholinergic receptors
How does pilocarpine treat narrow angle glaucoma attack?
Miotic action - It causes the ciliary muscle (M3 receptors) to contract produces accomodation, this is due to relaxation of suspensory ligaments, allowing lens to become more convex, and shift forward slightly. This leads to increased drainage of aquesous humor, by widening Canal of Shclemm, decreasing introcular pressure
How do you reverse mydriasis produced by atropine?
Pilocarpine
What should you watch for in administration of muscarnic agonists?
Exacerbation of COPD, asthama, and peptic ulcers
Why are muscarinic agonist contraindicated in asthma?
Increase bronchial secretion, stimulate bronchial smooth muscle contraction, precipiate asthma attack
Why are muscarinic agonist contraindicated in peptic ulcer disease?
Increase acid secretion
What is the classic muscarine receptor antagonist?
Atropine
What is atropine?
Plant alkaloid (found in belladonna, jimson weed), potent and selective antagonist of muscarinic acetylcholine receptors
How does atropine dialate the pupil?
Blocks muscarinic receptors, blocks Ach action on circular fibers, circular fibers relax, pupil diameter increases
What are organ system effects of muscarinic antagonists?
Insert slide (similar to sympathetic response)
What muscarinic receptor antagonist has some selectivity?
Pirenzipine (M1>M2>M3)
Pirenzepine
Muscarinic Antagonist, Clinical Application - Peptic Ulcer Disease, Adverse Effects - Cardiac arrhythmia, malignant hyperthermia, anaphylaxis, seizure, Contraindications - Gastrointestinal obstruction, Considerations - Alternative or additive agents to standard peptic ulcer disease therapies (replace by proton pump inhibitors for H.pylori)
What muscarinic antagonist can be used to treat peptic uclers and why?
Pirenzipine - a muscarinic antagonist so you are stopping acid secretion (parasympathetic action)
