Pharmacology Flashcards
3 ways to block neuromuscular transmission:
Presynaptically - inhibiting ACh synthesis or release
Postsynaptically
How can you block neuromuscular transmission presynaptically through inhibiting ACh SYNTHESIS?
Block rate-limiting step of choline uptake
How can you block neuromuscular transmission presynaptically through inhibiting ACh RELEASE?
Not much specificity
How can you block neuromuscular transmission postsynaptically?
Interfering with actions of ACh on receptor - more specific
What can you use to inhibit ACh release?
Local anaesthetics
General inhalation also anaesthetics
Inhibitors/competitors of calcium
Neurotoxins
Examples of Inhibitors/competitors of calcium:
Magnesium ions
Some antibiotics
Some examples of Neurotoxins:
Botulinum toxin
What does BOTOX stand for?
Botulinum toxin - relaxes muscles underneath skin
Clinical uses of neuromuscular blocking drugs:
Endotracheal intubation
During surgical procedures
Intensive care
During electroconvulsive therapy
Structure of Nicotinic acetylcholine receptor:
Pore in centre
5x subunits
2 binding regions for ACh
Types of blockers for Nicotinic ACh receptors:
Agonists - depolarising
Antagonists - non-depolarising
Why are agonist drugs depolarising?
Stimulate pore opening
Why are antagonists non-depolarising?
Prevent ACh binding - pore remains closed
Examples of competitive non-depolarising antagonist blockers:
Tubocuraine
Atracurium
How do antagonists result in no activation of muscle action potential?
Prevent ACh binding by occupying site
Decrease motor end plate potential
Decreases depolarisation of motor end plate region
Example of depolarising agonist blocker:
Suxamethonium
How do agonists over-stimulate the cell?
Not metabolised by Acetylcholine esterase- prolongs activity of ACh at neuromuscular junction
How do depolarising agonist blockers result in no more action potentials being generated?
Persistent depolarisation of motor end plate and muscle membrane
Prolonged end plate potential
What does the prolonged depolarisation of muscle membrane caused by depolarising agonists result in?
Membrane potential above threshold for resetting voltage-gated sodium channels
Channels remain refractory - can’t reset
Phase 1 of depolarising block:
Muscle fasciculatations, then blocked
Repolarisation inhibited
Sodium channels remain inactivated
Phase 2 of depolarising block:
Desensitisation blockade - no depolarisation as receptors are refractory
Examples of non-depolarising blockers:
PARVM
P = Pancuronium (SE Tachycardia)
A = Atracurium (SE hypotension)
R = Rocuronium (SE Tachycardia)
V = Vecuronium (SE few)
M = Mivacurium (SE hypotension)
Side effects of Suxamethonium:
Bradycardia
Ways of degrading Atracurium:
Ester hydrolysis and Hofmann elimination
Rapid degradation
Ways to degrade Mivacurium:
Plasma cholinesterases
Ways to degrade suxamethonium:
Plasma cholinesterases
Ways to degrade Pancuronium:
Hepatic metabolism
Slow - longer duration of immobility
Ways to degrade Vecuronium:
Hepatic metabolism
Slow - longer duration of immobility
Ways to degrade Recuronium:
Unchanged in bile/urine
What do cholinesterases degrade?
Mivacurium
Suxamethonium
Types of cholinesterases:
Acetylcholinesterase - hydrolysis of ACh
Plasma cholinesterases
What inhibits cholinesterases enzymes?
Anticholinesterase drugs
What do anticholinesterase drugs do?
Increase ACh at neuromuscular junction
Decrease degradation - longer duration of ACh
Reversible or irreversible effects on enzyme
Effects of anticholinesterases:
CNS = convulsions
ANS - many effects
Effects of anticholinesterases on ANS:
SLUDGE
Salivation Lacrimation Urination Defecation GI upset Emesis
Clinical uses of anticholinesterases:
Anaesthesia
Alzheimer’s disease
Myasthenia Gravis
What is Myasthenia gravis?
Auto-immune reaction
Block receptor to ACh -> muscle weakness
What reverses effect of rocuronium and Vecuronium?
Selective binding agent
