Cholinergic Pharmacology Flashcards
What consists of the CND
Brain and Spinal Cord
Two parts of the PNS
Somatic (NMJ)
Autonomic
What chemical messengers are found in Somatic
ACh
What chemical messengers are found in autonomic
ACh and Noradrenaline
What chemical messenger acts in the Parasympathetic pathway
ACh
What neurotransmitter works in the sympathetic pathways
Noradrenaline
What can cholinergic receptors be categorised as
Nicotinic
Muscarinic
What type of receptor is Nicotinic
Ion channel
What type of receptor is Muscarinic
G-protein couples
Where are muscarinic receptors found
Parasympathetic system
Length of sympathetic preganglionic fibres vs parasympathetic
Sympathetic - shorter
Parasympathetic - longer
Why are sympathetic preganglionic shorter
Because the ganglia are closer to the spinal cord
Why are parasympathetic postganglionic fibres shorter
They synapse close to the target organ
What does ACh bind to in the somatic NS
Nicotinic receptors at the neuromuscular junction
Describe the processes that take place at the NMJ
- Acetyl CoA reacts with Choline to give ACh
- ACh stored in vesicles
- Vesicles fuses with membrane on pre-synapse
- ACh binds to Nicotinic cholingeric receptor
- Acetylcholinesterase breaks ACh to Choline and Acetate
Enzyme that catalyses process of choline + Acetyl CoA -> ACh
CAT (Choline acetyl transferase enzyme)
How does Botulinum Toxin effect the NMJ
Inhibits ACh vesicle release = paralysis by using proteases to degrade vesicle proteins
What two reasons do we use Botox for
- Cosmetic
2. Spasticity
Name a competitive NAChR antagonist
- Tubocurarine
How does Tubocurarine function
- Acts as a neuromuscular blockade by binding to 2 nicotinic ending sites preventing binding of ACh
Why do we give Tubocurarine
Has a muscle relaxant effect
2. Result in being conscious but aware of pain and paralysed
How do we reverse the block effect of Tubocurarine
Sugammadex
How does Sugammadex reverse block of Tubocurarine
Selective relaxant binding agent that encapsulates the blocker thereby preventing it from binding
Structure of Suxamethonium
2ACh stuck together
How does Suzamethonium effect the NMJ
Desensitises the receptor causing paralysis of skeletal muscle
How fast does Suxamethonium act
Fast and for short duration
Why does Suxamethonium stay in the NMj for a while
Poor substrate for ACH esterase can only be broken down by plasma cholinesterase
Name a reversible ACh esterase inhibitor
Neostigmine
How does Neostigmine work
Blocks Cholinesterase increasing ACh at the synaptic cleft
Remains for longer and stimulation lasts longer
When do we prescribe Neostigmine
Myasthenia Gravis - alors ACh to remain longer resulting in a stronger response
What is Myasthenia Gravis
Immune System produces antibodies against nAChR resulting in less receptors and weak skeletal muscles= response
How do irreversible inhibitors effect NMJs
Inhibit ACh Esterase causing ACh to build up
Twitching, severe weakness and paralysis at NMJ
How does irreversible inhibition effect mAChR
Salivation Defecation Urination Bradycardia Hypotension
How does ACh accumulation from irreversible inhibition effect CNS
Confusion
Loss of reflexes
Convulsions
Coma
Role of the autonomic nervous system
Fine tunes function of organs
Role of Pilocarpine
Stimulates saliva in patients with dry mouth
Causes constrictor muscle and ciliary muscles to contract (miosis)
Improved filtration of aqueous fluid
Lowers intraocular pressure
What is Pilocarpine an agonist of
M3 (partial agonist)
Define miosis
Excessive constriction of pupil
When do we give Pilocarpine for adjusting intraocular pressure
For Glaucoma
What receptors mediate the parasympathetic pathway in the lungs
M3
What happens during excessive M3 receptor activation in the lung
Bronchoconstriction
Where is bronchoconstriction mediated by M3 seen
COPD
Asthma
What two types of antagonists do we have for M3 receptors in the lung
Ipratopium (short acting) and tiotropium (Long acting)
these act as bronchodilators
Each action in the bladder
Contraction of the bladder
Result of bladder agonist
More bladder contraction (urinary retention)
Result of using a bladder antagonist
Relaxes bladder
Example of a bladder agonist
Bethanechol
Example of a bladder antagonist
Oxynutinin
How does ACh effect the GI tract
Increase GI motility
What are mebeverine and scopolamine examples of
Gi antagonists
Why would we prescribe mebeverine and scopolamine
Irritable Bowel Syndrome
What is the adverse effects of muscarinic agonists
D- diarrhoea U- rination M- iosis B- Radycardia E- mesis L- agrimation S- alivation
What is a competitive antagonist at the nAChR at the autonomic ganglia
Hexamethonium
How does hexamethonium work
Blocks both the parasympathetic and sympathetic divisions of the autonomic nervous system
Does hexamethonium effect the NMJ
No
Four effects of parasympathetic autonomic block
- Secretions reduced
- Constipation
- Urinart retention
- Blurred vision
What is a sympathetic block a marker of at the autonomic level
Hypotension
When is hexamethonium given
As an antihypertensive
What does ACh regulate in the brain
Vomiting centre
What drug is given for motion sickness treatment and why
Scopolamine (anti-muscarininc)
How do we treat Parkinsons
Benxatropine blocks reuptake of ACh and increases dopamine at cleft
Why does Alzheimers occur
Lack of cholinergic neurones and reduction in ACh
How do we treat Alzheimers
Donepezil to inhibit ACh esterase increasing ACh in CNS (only works in CNS)
