neuromuscular blocking drugs

Question 1

nAChR at NMJ compared to at ganglion

Answer 1

different to ganglionic nAChr, hence drugs can be produced which are MORE selective for these receptors (present on skeletal muscle ie NOT ANS)

Question 2

ACHR- what type and subunits

Answer 2

nicotinic receptor with 2 alpha subunits (where ACh) binds, and 1 beta, gamma and delta

Question 3

sites of drug action and drugs involved

Answer 3

spinal cord- spasmolytics eg diazepam (reduces production of A.P’s) conduction of nerve via motor neurone- local anaesthetics (block sodium channels) ACH release- neurotoxins + Ca2+ blockers depolarisation and NMJ- TUBOCURARINE and SEXAMETHONIUM AP propagation within muscle fibre- spasmolytics eg dantrolene (block Ca2+ release from SR)

Question 4

what neuromuscular blocking drugs do, types and what they don’t do

Answer 4

always work on postsynapatic membrane- dont affect ACH release or propagation either non-depolarising eg tubocurarine/atracurium (COMPETITIVE antagonists) or depolarising eg sexamethonium (AGONIST) don’t cause loss of conciousness OR pain

Question 5

molecular structures of tubocurarine and sexamethonium

Answer 5

tubo has quarternary ammonium group- similar in strucutre, so binds, but no effficacy sexa is 2 ACH molecules bound together

Question 6

sexamethonium- how it works

Answer 6

agonist, so overstimulates nicotinic receptor, leading to receptors shutting down- initially causes muscle twitches (fasciculations), then FLACCID paralysis (muscle relaxes)

Question 7

pharmacokinetics of sexamethonium

Answer 7

given intravenously rather than orally as highly charge- broken down by pseudocholinesterase , so has a SHORT duration of paralysis

Question 8

uses of sexamethonium

Answer 8

endotracheal intubation- relaxes muscles in trachea to allow tube to go down for eg general anaesthetics muscle relaxant for ECT (therapy for severe depression)

Question 9

unwanted effects of sexamethonium

Answer 9

muscle pains (due to fasciculations) bradycardia- it can bind to muscarinic receptors in heart hyperkalemia- patients with burns will have hypersensitive muscle ie more receptors, hence AP causes large K+ efflux= heart issues increase in intraocular pressure- avoid for glaucoma

Question 10

tubocurarine mechanism effects DIAGRAM

Answer 10

simply competitive agonist- leads to flaccid paralysis as well but no fasiculatons- end plate potential (after stimulus artefact) on diagram not enough to fire A.P efffects extrinsic eye muscles first, then muscles of face, pharynx and limbs, then respiratory muscles- in recovery, other way round: respiratory recover first

Question 11

uses of tubocurarine and what can reverse it

Answer 11

relaxes muscles during surgery= less anaesthetic needed= safer allows articificial ventilation by switching off respiratory muscles reversed by anticholinesterase= more ACH

Question 12

pharmacokinetics of tubocurarine and when atracurium given instead

Answer 12

given intravenously as well, but longer duration of action excretion occurs via urine or bile, so if renal/liver failure, duration of action longer, so atracurium given instead

Question 13

side effects of tubocurarine

Answer 13

hypotension- high dosage can spill over to ganglia as well, blocking it, as well as causing histamine release tachycardia- in response to hypotension, and fact that vagus ganglia blocked bronchospasm and excessive secretions due to histamine release apnoea- due to respiratory muscles relaxation, so artificial ventilation often given