Neuromuscular Blocking Drugs Flashcards
pathway in neuromuscular transmission?
- ACh produced via cholineacetyl transferase (CAT)
- Ca2+ influx
- ACh excytosis
- ACh binds to receptors
- Na+ influx into muscle
- AChesterase breaks own ACh
- recycling by uptake
why are drugs selectively made for the somatic nervous system?
NMJ nAChR is different in structure to the ganglionic (ANS) nAChR
name a :
-competitive
-non-depolarising
NM blocking drugs (NMBD)
tubocurarine
atracurium
depolarising NMBD
suxamethonium (succinylcholine)
the subunits of nAChR
alpha 1 alpha 2 beta delta gamma
what subunit of the nAChR does ACh bind to?
only the alpha units
domain of the nAChR
expanses across the phospholipid bilayer
larger extracellular domain than intracellular
location and density of nAChR
very high density present on motor-end plates
outline the pathway of motor action and the significance of these sites
central processes conduction of nerve AP in motor neurone ACh release depolarisation of MEP AP initiation AP propagation along muscle fibre muscle contraction
these are all possible sites of drug actions to cause skeletal muscle relaxation
which drugs can target central processes?
spasmolytics e.g diazepam, baclofen
relieve spasm of muscles
what can target the conduction of AP in motor neurone?
local anaesthetic
inhibits sodium influx to reduce propagation
what can target the release of ACh?
hemicolinium
Ca2+ entry blockers
neurotoxins
these inhibit the re-uptake of choline and therefore its release later
what can target the post-synaptic MEP?
tubocurarine
suxamethonium
what can target the AP conduction along the muscle fibres?
spasmolytics e.g. dantrolene
what type of drug is tubocurarine
another example of a drug of this category
non-depolarising
competitive nAChR antagonist
also eg. atracurium
what type of drug is suxamethonium?
depolarising nAChR agonist causing a depolarising block
do these drugs affect consciousness or pain sensation?
no analgesic effects, they just relax muscles
but they are administer by anaesthetist
what aid must be provided due to the relaxant nature of NMBDs?
respiration must be assisted ,as the diaphragm is relaxed, until the drug is inactive or antagonised
what is a depolarising block (that caused by suxamethonium)?
what are the consequences of this?
a long time is taken to breakdown in the synaptic cleft
therefore causes fasciculations (brief twitches of muscles fibres) and eventually flaccid paralysis (loss of tone)
pharmokinetics of suxamethonium
IV administration as it is higher charged
duration of paralysis is ~5 min (short)
metabolised by pseudo-cholinesterase in the liver and plasma
where and how is suxamethonium metabolised?
by pseudo-cholinesterase in the liver and plasma
what are the two main uses of suxamethonium?
1) intubation by relaxing the vocal chords
2) muscle relaxant for electroconvulsive therapy
what are the unwanted effects of suxamethonium?
- post-op muscle pains
- bradycardia (direct muscarinic action of the heart)
- hyperkalaemia due to soft tissue injuries or burns–> ventricular arrhythmias/MI
- increase in IOP (therefore avoid treating with glaucoma patients)
what extent of blockage is needed for tubocurarine to be effective?
70-80% blockage is needed to cause skeletal muscle relaxation
what is the effect of tubocurarine of different muscles
flaccid paralysis in order:
1) extrinsic muscles of the eye (causes double vision)
2) small muscles of the face, limbs and pharynx
3) respiratory muscles
recovery works backwards in rewinding the effects i.e. eye muscles are blocked first and recover last
2 main uses of NMBD tubocurarine
1) relaxation of skeletal muscles during surgical op
- so less anaesthetic can be used
2) allows for artificial respiration to be given as it relaxes the resp muscles
what drugs reverse the effects of non-depolarising drugs like tubocurarine?
anticholinesterases e.g. neostigmine
pharmokinetics of tubocurarine
- IV due to high charge
- does not cross BBB or placenta
- paralysis lasts ~40-60 mins (long)
metabolism of tubocurarine
is not metabolised by excreted in urine (70%) and bile (30%)
why is it hard to administer tubocurarine to renal or hepatic function impaired patients ?
due to the excretion pathways of tubocurarine in the urine and bile
what should be given to the renally and hepatically impaired? why?
atracurium
lasts 15 mins
chemically unstable
unwanted effects of tubocurarine?
- ganglionic block
- histamine release
therefore:
1) Hypotension –
- ganglion blockade lowers TPR
- histamine release causes vasodilation.
2) Tachycardia –
- reflex tachycardia (hypotension)
- also due to blockade of vagal ganglia.
3) Bronchospasm, excessive secretions –
- histamine release causing bronchoconstriction.
4) Apnoea – thus ALWAYS assist respiration.
NMBDs interferes with…
respiration
why is suxamethonium contra-indicated in glaucoma?
increased IOP
what is the main effect of NMDBs?
paralysis (flaccid)
what is the difference in duration of action between depolarising and non-depolarising NMBDs?
depolarising drugs last a short time while non-depolarising (competitive) drugs last for a long time
