Week 6 Pharmacology - ANS/PNS/CNS Flashcards
What are the different types of muscarinic receptors, and their effect?
Which doesn’t use the IP3 and DAG second messenger system?
M1 = CNS neurons
M2 = myocardium, smooth muscle, opening of K+ channels and inhibition of adenylyl cyclase (doesn’t use IP3/DAG system)
M3 = exocrine glands, blood vessels (smooth muscle and endothelium)
Also M4,5 –> CNS and CNS vasculature
What is the effect of a1 receptor stimulation?
GCPR: IP3+DAG –> inc. Ca2+
Smooth muscle contraction (vasculature, sphincter)
Pupil dilation
What is the effect of a2 receptor stimulation?
GPCR Inhibition of adenylyl cyclase and decreased cAMP
Most important function is presence on presynaptic nerve terminals, and binding to a2 will inhibit release of further noradrenaline from neuron
What is the effect of B1 receptor stimulation?
Stimulation of adenylyl cyclase, increased cAMP
Increased cardiac contractility and chronotropy
Increased renin release
What is the effect of B2 receptor stimulation?
GPCR increased cAMP
Smooth muscle relaxation (i.e. bronchial, vascular)
Potassium uptake
Activates gylcogenolysis
What receptor/neurotransmitter causes activation of sympathetic fibres from sympathetic chain?
Action of acetylcholine on nicotinic ion receptors, Na+ entry –> depolarisation
What are the two different categories of cholinomimetics?
Sympathomimetic
Parasympathomimetic
What is the difference between direct and indirect cholinomimetic agents?
Direct = ligand binding to cholinoceptors
Indirect = inhibition of cholinesterase –> increased endogenous ACh
What is the clinical usefulness of cholinesterase inhibitors (i.e. neostigmine, physostigmine) ?
Myasthenia gravis
Reversal of non depolarising neuromuscular blockers (rocuronium)
What is the mechanism of action of atropine?
Reversible blockage of muscarinic receptors by binding and inhibiting action of GPCR downstream signalling (IP3/DAG or adenylyl cyclase)
What receptors is atropine selective for? What is an example of selective M3 antagonist?
M1-M3
Oxybutinin is M3 antagonist
What is the reason for low dose atropine causing bradycardia?
In small doses it can block the post-ganglionic M1 receptors first which lead to increased ACh release from parasympthetic fibres before peripheral blockade occurs (why always start with big dose atropine in bradycardia)
What are the clinical effects of atropine/antimuscarinics?
Dry as a bone
Blind as a bat
Mad as a hatter
Red as a beet
Hot as a hare
Tachycardia
What are examples of a1 receptor agonists?
Phenylephrine
Milodrine
**Can cause reflex bradycardia
What is the mechanism of Metaraminol?
Indirect a1 actions via displacing noradrenaline from nerve endings.
In higher doses may have direct action.
