Neuromuscular Blocking Drugs

Question 1

NAchR at neuromuscular junction = different to ganglionic nAChR

Answer 1

Selectivity

Question 2

Sites of drug action at the neuromuscular junction

Answer 2

Central processes
      - spasmolytics (diazepam, baclofen)
Conduction of nerve AP in motor neuron
      - local anaesthetics
ACh release
      - hemicholinium
      - Ca2+ entry blockers
      - neurotoxins
Depolarisation of motor end-plate —> AP initiation
      - tubocurarine
      - suxamethonium
Propagation of AP along muscle fibre + muscle contraction
     - spasmolytics (dantrolene)

Question 3

What are the two types of neuromuscular blocking drugs?

Answer 3

Non-depolarising (competitive antagonist)

Depolarising (agonists)

Question 4

TRUE OR FALSE

Neuromuscular blocking drugs affects consciouness

Answer 4

FALSE

They DO NOT affect consciousness

Question 5

TRUE OR FALSE

NM blocking drugs do not affect pain sensation

Answer 5

TRUE

Question 6

NM blocking drugs always assist respiration (until drug inactive or antagonised)

Answer 6

CLOZE

They’re used before surgery to relax the skeletal muscle

Question 7

Give an example of a depolarising NM blocker

Answer 7

Suxamethonium

Question 8

What is the mechanism of action of suxamethonium?

Answer 8

Extended end plate depolarisation —> ‘depolarisation block’ (phase 1)
Overstimulate nicotinic receptors
Receptors shut down (don’t like being overstimulated)
Nicotinic receptor agonist
Diffuses slowly into muscle
Fasciculations (muscle twitching) —> flaccid paralysis
Not rapidly broken down like ACh
Muscles relax

Question 9

Neuromuscular lblocking drugs have postsynaptic action

Answer 9

CLOZE

Question 10

What are the pharmacokinetics of suxatmethonium?

Answer 10

Route of administration = IV (highly charged)
Duration of paralysis = around 5 min (short)
Metabolised by pseudo-cholinesterase in liver and plasma

Question 11

What are the uses of suxamethonium?

Answer 11

Endotracheal intubation

Muscle relaxant for ECT (electro convulsive therapy - used for severe clinical depression)

Question 12

What are the unwanted effects of suxamethonium?

Answer 12

Post-operative muscle pains
Bradycardia
- direct muscarinic action on heart (atropine)
Hyperkalaemia
- soft tissue injury or burns (leads to denervation supersensitivity) —> ventricular arrhythmias.cardiac arrest
- avoid suxamethonium to avoid hyperkalaemia (give non-depolarising instead)
Increased intra-ocular pressure
- avoid for eye injuries, glaucoma

Question 13

Name a non-depolarising NM blocker

Answer 13

Tubocurarine

NOTE: non-depolarising NM blockers all have the same mechanism of action, only differs in duration of action

Question 14

What is the mechanism of action of tubocararine?

Answer 14

Competitive nAChR antagonist

70-80% block necessary for maximum flaccid paralysis

Question 15

What are the effects of tubocararine?

Answer 15

Flaccdi paralysis

Order of effects:
1. Extrinsic eye muscles (double vision)
2. Small muscles of face, limbs, pharynx
3. Respiratory muscles
During recovery, order is reversed

Slide 11 [pic]

Question 16

What are the uses of tubocararine?

Answer 16

Relaxation of skeletal muscles during surgical operations (=less anaesthetic)
Permit artificial ventilation

Question 17

Actions of non-depolarising blockers can be reversed by anticholinesterases

Answer 17

CLOZE
E.g. neostigmine (and atropine)
Atropine = damps down muscarinic receptor overstimulation
Raise endogenous ACh, overcome competitive block

Question 18

Whata re the pharmacokinetics of tubocararine?

Answer 18

Route of action = IV (highly charged0
Does not cross BBB or placenta
Duration of paralysis = 1-2 hours (long)
Not metabolised
Excretion: 70% in urine, 30% bile (care if renal or hepatic function impaired)
- Atracurium (15min, chemically unstable)
- designed to be chemically unstalbe at physiological pH
- hydrolysed to 2 inactive fragments over a 15 min period
- used for people with impaired hepatic or renal function

Question 19

What are the unwanted effects of tubocararine?

Answer 19

Ganglion block and histamine release

Hypotension
     - ganglion blockade (lowers TPR)
     - histamine release from mast cells (leakage of histamine as tubocararine = basic)
Tachycardia (may —> arrhythmias)
     - reflex
     - blockade of vagal ganglia
Bronchospasm (histamine release)
Excessive secretions (bronchial and salivary) (histamine release)
Apnoea (always assist respiratory)

Question 20

The clincial use of neuromuscular blocking drugs will most likely involve interference with which of the follwoing phsyiological processes?

1. Kidney functiono
2. Consciousness
3. Body temperature regulation
4. Pain sensation
5. Respiration

Answer 20

5

Question 21

Which of the following effects would be observed with a non-depolarising nuermomusclar block?

1. Initial muscle fasciculations
2. Irreversible nAChR blockade
3. The block would be enhanced by anticholinesterase drugs
4. A flaccid paralysis
5. Increased arterial pressure

Answer 21

4