Patient: Cholinergic drugs Flashcards
Difference between muscarinic and nicotinic acetylcholine receptors
Muscarinic: G-protein coupled, slow
Nicotinic: ligand-gated ion channel, fast transmission
Name 3 sites of action for nicotinic acetylcholine receptors
CNS, NMJ, autonomic ganglia
Name 3 sites of action for muscarinic acetylcholine receptors
CNS, Parasympathetic nervous system, sympathetic nervous system
Describe nicotinic acetylcholine receptors using this:
1) -meric
2) number of subunits and receptor subtypes
3) built in/g protein
4) number of Ach sites
5) speed of response
1) Pentameric
2) 18 subunits of multiple types
3) built in ion channel
4) 2 Ach sites
5) microseconds to milliseconds
Describe muscarinic acetylcholine receptors using this:
1) -meric
2) number of subunits and receptor subtypes
3) built in/g protein
4) number of Ach sites
5) speed of response
1) Monomeric
2) M1-5 subtypes, 5 receptor sites
3) Binding site for G protein
4) 1 Ach site
5) milliseconds to seconds
Agonists of nicotinic acetylcholine receptors
nicotine, suxamethonium
Antagonists of nicotinic acetylcholine receptors
atracurium, tubocurarine, alpha-bugarotoxin
Agonists of muscarinic acetylcholine receptors
pilocarpine, muscarine
Antagonists of muscarinic acetylcholine receptors
atropine, hyoscine
Drugs acting at ACh
Paralyzing agents used in surgery* Drugs to treat nicotine addiction* Anti-emetic drugs* Anti-asthma drugs* Drugs used in eye exams Drugs used to treat glaucoma ?Alzheimer’s disease drugs* ?Parkinson’s disease drugs ?Anti-schizophrenia drugs
Drugs acting on ACh metabolism/release
ACh esterase (AChE) Drugs to treat myasthenia gravis* Drugs to treat Alzheimer’s disease* Drugs to treat glaucoma Nerve gases, insecticides* ACh release Botox*
Name two type of blockers to neuromuscular transmission
mechanism-wise
Competitive antagonists at nAChR (flaccid paralysis)
Depolarising blockers agonists at nAChR
How to reverse the effect of a competitive antagonist at the nAChR
Can be reversed by AChE inhibitors
Can depolarising blockers (agonists at nAChR) be reversed with AChE inhibitors?
No
Name a use of a neuromuscular transmission blocker
muscle relaxation in surgery
Muscle relaxation doing surgery.. name some drugs which use the competitive antagonist of nAChR route
Atracurium Pancuronium Vecruonium Gallamine Tubocurarine
Muscle relaxation doing surgery.. name some drugs which use the depolarising blocker agonists at nAChR route
Suxamethonium
Decamethonium
What is Suxamethonium hydrolysed by? How long does it work for?
serum ChE
fast recovery - 3 minutes
How does Atracurium break down?
Spontaneously breaks down
Duration of action for Pancuronium? Uses?
100-200 minutes
Used for euthanasia and executions
Tell me about a receptor involved in nicotine addiction/smoking cessation
Receptor containing α4 and β2 subunits may be important in nicotine addiction
Varenicline (Champix) = partial agonist at α4β2 receptor.
NICE concludes it is cheaper long term than NRT or bupropion
Are agonists used with muscarinic drugs? Name two
Agonists not widely used apart from Pilocarpine in glaucoma and bethanechol in bladder disorders
Name 3 general effects of muscarinic antagonists
- tachycardia
- inhibits secretions (saliva, gastric acid)
- relaxes smooth muscle (GI tract, bronchi)
Name some therapeutic effects of muscarinic antagonists
Anti-emetic
Anti-parkinsonian
(Amnesia, sedation)
Name some muscarinic antagonists
Atropine
Tiotropium, ipratropium
Hyoscine
Darifenacin, solifenacin
Use of Atropine
Prevent bronchial secretions during surgery
Use of Tiotropium and ipratropium
Inhaled bronchodilators in asthma
quaternary ammonium salts so not absorbed systemically
Use of Hyoscine
treat motion sickness
Use of Darifenacin and Solifenacin
Treat M3 selective bladder hyperactivity
How does botulinum toxin work?
Blocks release of ACh by breaking down SNARE proteins
Effects of botulinum
Paralysis of skeletal muscle, autonomic block
systemic effects can cause death
Use of botulinum
Can be used to paralyse muscles on a local basis
muscle spasm treatment and cosmetic wrinkle removal
List some irreversible acetylcholinesterase inhibitors
Sarin, VX
What are sarin and VX used for?
irreversible acetylcholinesterase inhibitors
nerve gases and insecticides
causes muscle paralysis and over-activation of the autonomic nervous system (especially the parasympathetic route)
How to counteract the effects of sarin and VX
Atropine can counter some symptoms via mAChR
Pralidoxime regenerates enzyme if administered within five hours.
Name some competitive reversible AChEsterase inhibitors
Edrophonium
Physostigmine
Neostigmine
Rivastigmine
Name some non-competitive reversible AChEsterase inhibitors
Tacrine
Donepezil
When are reversible AChEsterase inhibitors used?
In situations where there needs to be a boost cholinergic transmission
Clinical uses of reversible AChEsterase inhibitors
Reversal of non-depolarizing NMJ blocker e.g. pancuronium
Autoimmune myasthenia gravis
immune attack on nAChR in NMJ. Increasing ACh boosts transmission via remaining receptors
increases muscle strength
edrophonium (test); pyridostigmine, neostigmine, physostigmine
Alzheimer’s disease
loss of cholinergic neurons
tacrine, donepezil
