Parasympathetic Pharmacology Flashcards
What are the characteristics of muscarinic receptors?
Activated by muscadine
All via metabotropic events
3 members family (M1 in brain, M2 in heart, M3 in SM)
Use second messenger
Where are the M subtypes localised and what is their effect
M2 in heart (SA node and atrial muscle) to decrease rate and force of contraction
M3 everywhere else
Bronchi (SM and glands) for constriction and secretion
GI tract (SM and glands) for contraction, increase motility and secretion
Bladder for contraction
Eye (pupil and ciliary muscle ) for constriction
Salivary glands for secretion
Lacrimal glands for secretion
What is the molecular mechanism of M2 receptors?
Indirect effect: G protein coupled to Gi so decrease d]adenylate cyclase upon binding so decrease cAMP and PKA so less contraction
Direct effect: open K+ channel to decrease membrane potential and therefore decrease firing of action potentials
What is the difference in mechanism between M3 and M2?
M3 (glandular) increase calcium to cause exocrine secretion and SM contraction
M2 (cardiac) decrease cAMP, PKA and phoshorylation of calcium channels therefore rendering them inactive . Also activates K+ channels for hyperpolarization. Result is bradychardia
What is the therapeutic use of muscarinic receptor antagonists?
Oxybutynin, non-selective M2 and M3
Prevent unwanted bladder contraction
SE: blurred vision, tachycardia, dry mouth
Give an example of a muscarinic (M3) agonist and antagonist
Agonist: pilocarpine
Antagonist: atropine
What is pilocarpine used for?
Treat glaucoma (build up of intraocular pressure which can compress the optic nerve, also XS aqueous humour) Pilocarpine constrict the circular muscle and opens up drainage channel to increase drainage of aqueous humour therefore decreasing intraocular pressure
What is tropicamide?
Muscarinic antagonist used to facilitate ocular examination by causing mydriasis
What is scopolamine (hyoscine)?
Non selective musc receptor antagonist
Crosses BBB to depress the CNS
Used for sedation, motion sickness prevention, reduce bowel colic and inhibition of SM motility
How does one terminate Ach neurotransmission?
Using AChE which hydrolyse Ach into acetate and choline
Give examples of anti-AChE and their use
Physostigmine (increase mitosis in treatment of glaucoma, stimulate bladder urinary retention, treat atropine poisoning)
Neostigmine (polar and less lipophilic) acts peripherally and more effective at NMJ, used to treat myasthenia gravies
Give example of irreversible AChE
Dyflos.
Non-competitive inhibitor of AChE
Binds to enzymes and make it lose function
Uses as pesticides and insecticides
Can cause poisoning which is treated with atropine and oximes (like pralidoxime) which can dephosphorylate AChE and make it active again therefore reducing effects of organophosphate poisoning.
