Neuromuscular blocking drugs

Question 1

what branch of the NS is neuromuscular transmission dealing with?

Answer 1

• SOMATIC

Question 2

describe NM transmission

Answer 2

• production of ACh using CAT
• AP propagation
• Ca2+ influx
• ACh exocytosis
• ACh binds to receptors and Na+ influx
• ACh esterase breaks down ACh
• recycling by uptake

Question 3

name the 3 most important NM-blocking drugs

Answer 3

competitive - tubocurarine, atracurium

depolarising - suxamethonium

Question 4

what makes up the nicotinic acetylcholine receptor?

Answer 4

5 subunits: alpha 1, alpha 2, beta, delta, gamma

ACh only binds to alpha receptor

Question 5

where is the density of these receptors high?

Answer 5

motor end plate

Question 6

give examples of spasmolytics and their MoA

Answer 6

e. g. Diazepam, Baclofen
- target central processes within nerve cell
- spasmolytics relieve spasm of muscles

Question 7

what is the MoA of local anaesthetics?

Answer 7

inhibit influx of Na and so reduce propagation of AP along nerve

Question 8

what does Hemicolinium do?

Answer 8

• Ca2+ entry blockers
• neurotoxins
• inhibit re-uptake of choline

Question 9

what are non-depolarising NM-blocking drugs?

Answer 9

competitive antagonists

e.g. Tubocurarine, Atracurium

Question 10

what are depolarising NM- blocking drugs?

Answer 10

• agonists
• cause depolarising block
• Suxamethonium
• good at stimulating due to its VERY similar structure to ACh

Question 11

what is important to remember with these drugs?

Answer 11

• do not affect consciousness or pain sensation

- respiration must always be assisted

Question 12

what is the MoA of suxamethonium?

Answer 12

• causes a long depolarising block (takes a long time to break down in synaptic cleft)
• causes fasciculations –> flaccid paralysis

Question 13

what are the pharmacokinetics of suxamethonium?

Answer 13

• IV admin
• duration of paralysis is short (around 5 mins)
• metabolised by a pseudo-cholinesterase in liver and plasma

Question 14

what are the uses of suxamethonium?

Answer 14

• intubation (relaxes vocal chords)

- muscle relaxant for ECT

Question 15

what are the unwanted effects of suxamethonium?

Answer 15

• post op muscle pains
• bradycardia
• hyperkalaemia
• inc. in IOP

Question 16

what is the MoA of tubocurarine?

Answer 16

• competitive nAChR antagonist

- block of 70-80% needed to cause effect of skeletal muscle relaxation

Question 17

what are the effects of tubocurarine?

Answer 17

• flaccid paralysis

- flaccid paralysis affects muscles in specific order

Question 18

what is the order in which muscles are affected?

Answer 18

• extrinsic eye muscles
• small muscles of face, limbs, pharynx
• resp muscles
• recovery of this effect works backward

Question 19

what are the uses of non-depolarising NM-blockers?

Answer 19

• relaxation of skeletal muscles during surgical operations

- permits artifical ventilation

Question 20

how are these effects reversed?

Answer 20

using anticholinesterases

Question 21

what are the pharmacokinetics of tubocurarine?

Answer 21

• administered via IV
• does not cross BBB or placenta
• paralysis lasts long time (60 mins)
• not metabolised, excreted 70% urine, 30% bile

Question 22

what are the unwanted effects of tubocurarine?

Answer 22

causes ganglion block and histamine release

• hypotension (ganglion blockade lowers TPR and histamine release = vasodilation)
• tachycardia (reflex tachycardia)
• bronchospam, excessive secretions (histamine release causing bronchoconstriction)
• apnoea