Cholinergic effect Flashcards
Comment on pre-ganglionic nerve of cholinergic nerve
• Have a long pre-ganglionic nerve
What are parasympathomimetics?
Compound that mimics the stimulation of parasympathetic nerves
List of cholinoreceptors and what do they do?
○ List of cholinesterase inhibitors and they will all boost the level of Ach in the vincity of the receptor § Neostigmine § Physostigmine § Edrophonium § Parathion
What are cholinoreceptors separated into?
○ Cholinoreceptors are serperated into two branches
§ Nicotonic Ach receptors are LGICR
□ N1 or NM- Skeletal muscle
□ N2 or NN- Autonomic Ganglia(CNS)
§ Muscarinic receptors which are GPCR
□ M1- CNS, peripheral neurones, gastric pariteal cells
□ M2- Atria, SAN, AVN
□ M3- Visceral smooth muscle, secretory glands, endothelial cells
□ M4- CNS
□ M5- CNS
Nicotinic selective agonists
○ Nicotine
○ Lobeline
Nicotinic selective antagonists
○ Tubocararine
○ Hexamethonium
○ Pancuronium
Muscaranic selective agonists
○ Muscarine
○ Bethanecol-relatively resistant to cholinesterase’s
Pilocarpine
Muscaranic selective antagonists
○ Atropine
○ Hyoscine
○ Pirenzepine
○ Ipratopium
Muscaranic selective antagonists
○ Atropine
○ Hyoscine
○ Pirenzepine
○ Ipratopium
Stimulation of nAChr and its termination
- Ach binding produces a conformational change that opens channel pores
- Allows influx of cations
- Produces an excitatory junction potential in the target cell
- Effect terminated by unbinding of Ach
Main parasympathetic effects
- Reduce heart rate
- Vasodilation
- Increased saliva and gastric acid production
- Increased tear formation
- Visceral smooth muscle contraction
- Pupil constriction
What is limited in cardiac cells?
• Limited parasympathetic innervation to the heart
Where does parasympathetic innervation only go to in the heart?
• Only goes to atria and pacemaker cells
What parts of the heart does the vagus nerve effect
SAN and atria
When vagus nerve stimulated…
○ Membrane potential hyperpolarises
○ Frequency slows
○ Aps decrease
How is the heart rate reduced?
• M2 receptor in heart is negatively coupled to cAMP
○ Less cAMP so pacemaker channels will be less active
○ Less PKA so less calcium channel activity
○ The beta-gamma subunits dissociate and interact with a potassium channel(GIRK)
○ Potassium channel is open all the time and will drive the membrane potential more negative
○ Also suppresses action potentials so more depolarisation needed to get the action potential hence heart rate slows down
What are the vascular effects?
Arterial relaxation
How are smooth muscles relaxed?
• Arteries do express M3 receptors
○ Receptors located on endothelial cells of blood vessels
○ Endothelium releases NO which is made from arginine by NO synthase
○ No synthase is calcium activated
○ NO binds to guanylyl cyclase
○ GTP goes to cGMP
○ Leads to rapid relaxation of smooth muscle cells
Equation for blood pressure
Blood pressure=cardiac output x peripheral resistance
Contraction of non-vascular smooth muscles(Activation of M3 receptors)
○ Increased activation of phospholipase C
○ Calcium release
Examples of non-vascular smooth muscles
GI tract
Bladder
Airways
Effects on secretory cells and the receptor stimulated
• Acetylcholine from vagus augments acid production(M1)
• Salivary glands(M3)
• Sweat glands(M3)
○ Are under sympathetic control
Effects on eye
Where are parasympathetic nerves found?
• Parasympathetic receptors found on circular muscle
Effects on eye
What do sympathetic nerves innervate?
• Sympathetic nerves innervate the radial muscle
What does the stimulation of cholinergic receptors in eyes do?
• Contraction of ciliary muscle
• Relaxes suspensory ligaments
Allows lens to bulge
How is glaucoma arisen and what is it often due to
- Glaucoma stems from poor drainage of fluid through trabecular network
- Often due to a dilated iris
Directly acting parasympathomimetics
○ Piolocarpine(mAchR agonist) § Used to treat glaucoma and dry mouth § Used in sweat tests ○ Bethanecol(mAchR agonist) § Occasionally used to aid bladder/gastric emptying ○ Succinylcholine § High affinity nAChR agonist which is used in surgery § Depolarising paralysis
Clinical uses of muscaranic blockers
- Premedication before anaesthesia to reduce secretions, sedations(hyoscine), prevent vagal effects
- In the heart, they block to increase AV conduction
- Ophthalmology-used to produce mydriases for examination
- Bronchodilation in COPD
- Anti-spasmodic in GI colic
- Treatment of antiChE poisoning
- Motion sickness
Clinical uses of nicotinic blockers
• Muscle relaxants
• Direct nAChR blocker:
○ Tubocurarine
○ Pancuronium
○ Vecuronium
○ Atacurium
• Depolarising blockers
• Direct nAchR agonists
Suxamethonium
