Neuromuscular blocking drugs Flashcards
Recall what neurotransmitter is used at the NMJ?
ACh from motor neuron (straight from spinal chord ventral horn)
Nothing to do with autonomic nervous system
Recall how ACh transmits the AP across the NMJ?
As AP arrive to presynapse-Ca enters the cells-cause release of ACh vesicles into junction
ACh releases activates Na+ channels on post synpatic, depolarise other cell (graded potential-depends on the amount of ACh released)
Then ACh breakdown by cholinesterase then recycled
Are the NMJ ACh receptors the same as in the ANS ganglions?
No-both nicotinic receptors but have a slight different structure–drugs can target them independently
(alpha subunits of nicotinic-remember 5 subunits etc)
Theoretically, where could drugs interefere with Neuromuscular transmission?
Central processes-Spasmolytics
Conduction of the nerve-local anesthetics (block Na+)
ACh release-Ca2+ entry blockers
Depolarisation of motor end-plate-Tubocurarine
Propagation of AP along muscle-Spasmolytics
What are the main NM blocking drugs?
2 classes-postsynaptic action
1-non depolarising blocker (competitive antagonists)-Tubocurarine
2-depolarising (agonists) -> Suxamethonium
Do NM blockers affect pain and consciousness?
No, neither of them do on either
when given always assist respiration
What are the mechanisms of action of suxamethonium?
nAChR---agonist -causes Extended and disorganised depolarisation, which causes a depolarisation block (Phase 1)-shut down because over stimulated initially twitches (fasciculations)-Causes flaccid paralysis
What are the pharmacokinetics of suxamethonium?
Acts about over 5min (short acting)-
metabolised by pseudo-cholinesterase in liver and plasma
What are the main uses of Suxamethonium?
endotracheal intubation-to put tube for investigation, anaeatetics, etc
Muscle relaxant for ECT (Therapy for depression that doesnt respond to drugs-electroconvuslive therapy)
What are the main side effects of Suxamethonium?
Post operative muscle pain (due to fasciculations)
Bradycardia (muscarinic action on heart-atropine to fight it)
Hyperkalemia (in some injury, damage to NMJ can reduce input-and more Nicotinic receptors around-injury hypersensisivity-and when give drugs cause massive Na influx-can cause arrythmia)
Intra-occular pressure rise-avoid in eye injury/glaucoma
What is the mechanism of action of Tubocurarine (Non depolarising blockers)?
Tubocurarine is naturally occuring (now have synthetic)
Competitive nAChR antagonist-need to block 70%/80% blockage to affect the blockage
No muscle twithc-but flaccid paralysis
(Extrinsic eye muscle -> small muscle of face, limbs, pahrynx -> respiratory -> (inverse when recover)
What are the uses of Tubocurarine?
Relaxation of skeletal muscle during surgery-less anesthetics needed
To allow fully automated ventilation
What can reverse the actions of tubocurarine?
All non-depolarising drugs can be reversed by anticholinesterases
Neostigmine (+Atropine)
What are the main pharmacokinetics of Tubocurarine?
Does not cross BBB/plasma
Acts for about 1-2h
is NOT metabolised but excreted in urine (70%) and bile (care if impaired)-instead use atrocurine (unstable-so breaks fast)
What are the side effects of Tubocurarine?
Hypotension-ganglion blockage+release of histamine (leaks as tubo is alkaline)
Tachycardia-reflex to hypotens and blockage of vagal ganglia
Bronchospasm, excressive secretion (histamine release)
Apnoae (always assist respiration
