Neuromuscular Blocking Drugs

Question 1

pathway in neuromuscular transmission?

Answer 1

• 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

Question 2

why are drugs selectively made for the somatic nervous system?

Answer 2

NMJ nAChR is different in structure to the ganglionic (ANS) nAChR

Question 3

name a :
-competitive
-non-depolarising
NM blocking drugs (NMBD)

Answer 3

tubocurarine

atracurium

Question 4

depolarising NMBD

Answer 4

suxamethonium (succinylcholine)

Question 5

the subunits of nAChR

Answer 5

alpha 1
alpha 2
beta
delta 
gamma

Question 6

what subunit of the nAChR does ACh bind to?

Answer 6

only the alpha units

Question 7

domain of the nAChR

Answer 7

expanses across the phospholipid bilayer

larger extracellular domain than intracellular

Question 8

location and density of nAChR

Answer 8

very high density present on motor-end plates

Question 9

outline the pathway of motor action and the significance of these sites

Answer 9

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

Question 10

which drugs can target central processes?

Answer 10

spasmolytics e.g diazepam, baclofen

relieve spasm of muscles

Question 11

what can target the conduction of AP in motor neurone?

Answer 11

local anaesthetic

inhibits sodium influx to reduce propagation

Question 12

what can target the release of ACh?

Answer 12

hemicolinium
Ca2+ entry blockers
neurotoxins

these inhibit the re-uptake of choline and therefore its release later

Question 13

what can target the post-synaptic MEP?

Answer 13

tubocurarine

suxamethonium

Question 14

what can target the AP conduction along the muscle fibres?

Answer 14

spasmolytics e.g. dantrolene

Question 15

what type of drug is tubocurarine

another example of a drug of this category

Answer 15

non-depolarising
competitive nAChR antagonist

also eg. atracurium

Question 16

what type of drug is suxamethonium?

Answer 16

depolarising nAChR agonist causing a depolarising block

Question 17

do these drugs affect consciousness or pain sensation?

Answer 17

no analgesic effects, they just relax muscles

but they are administer by anaesthetist

Question 18

what aid must be provided due to the relaxant nature of NMBDs?

Answer 18

respiration must be assisted ,as the diaphragm is relaxed, until the drug is inactive or antagonised

Question 19

what is a depolarising block (that caused by suxamethonium)?

what are the consequences of this?

Answer 19

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)

Question 20

pharmokinetics of suxamethonium

Answer 20

IV administration as it is higher charged
duration of paralysis is ~5 min (short)
metabolised by pseudo-cholinesterase in the liver and plasma

Question 21

where and how is suxamethonium metabolised?

Answer 21

by pseudo-cholinesterase in the liver and plasma

Question 22

what are the two main uses of suxamethonium?

Answer 22

1) intubation by relaxing the vocal chords

2) muscle relaxant for electroconvulsive therapy

Question 23

what are the unwanted effects of suxamethonium?

Answer 23

• 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)

Question 24

what extent of blockage is needed for tubocurarine to be effective?

Answer 24

70-80% blockage is needed to cause skeletal muscle relaxation

Question 25

what is the effect of tubocurarine of different muscles

Answer 25

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

Question 26

2 main uses of NMBD tubocurarine

Answer 26

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

Question 27

what drugs reverse the effects of non-depolarising drugs like tubocurarine?

Answer 27

anticholinesterases e.g. neostigmine

Question 28

pharmokinetics of tubocurarine

Answer 28

• IV due to high charge
• does not cross BBB or placenta
• paralysis lasts ~40-60 mins (long)

Question 29

metabolism of tubocurarine

Answer 29

is not metabolised by excreted in urine (70%) and bile (30%)

Question 30

why is it hard to administer tubocurarine to renal or hepatic function impaired patients ?

Answer 30

due to the excretion pathways of tubocurarine in the urine and bile

Question 31

what should be given to the renally and hepatically impaired? why?

Answer 31

atracurium
lasts 15 mins
chemically unstable

Question 32

unwanted effects of tubocurarine?

Answer 32

• 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.

Question 33

NMBDs interferes with…

Answer 33

respiration

Question 34

why is suxamethonium contra-indicated in glaucoma?

Answer 34

increased IOP

Question 35

what is the main effect of NMDBs?

Answer 35

paralysis (flaccid)

Question 36

what is the difference in duration of action between depolarising and non-depolarising NMBDs?

Answer 36

depolarising drugs last a short time while non-depolarising (competitive) drugs last for a long time