Neuromuscular Blocking Drugs

Question 1

Describe the stages of NM transmission

Answer 1

ACh is produced using CAT -> AP propagation -> Ca2+ influx -> ACh exocytosis -> ACh binds to receptors and Na+ influx -> ACh esterase breaks down ACh -> recycling uptake

Question 2

What are the 3 most important NM blocking drugs?

Answer 2

Tubocurarine, atracurium, suxamethonium

Question 3

Give examples of competitive (antagonists) NM blocking drugs

Answer 3

Tubocurarine and atracurium

Question 4

Give an example of a depolarising NM blocking drugs (cause depolarising block)

Answer 4

Suxamethasonium

Question 5

What factor means that it is possible to produce selective drugs for the somatic nervous system?

Answer 5

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

Question 6

What are the different subunits to the nicotinic acetylcholine recepor?

Answer 6

Alpha 1, Alpha 2, Beta, Delta and Gamma

Question 7

What is the structure of the nicotinic acetylcholine receptor?

Answer 7

There is a large extracellular domain and a slightly smaller intracellular domain

Question 8

What is the density of nicotinic acetylcholine receptors on the motor end plate like?

Answer 8

Very High

Question 9

What are sites of action of skeletal muscle relaxants?

Answer 9

• Central processes
• Conduction of nerve AP in motor neurone
• ACh release
• Depolarisation of motor end plate - AP initiation
• Propagation of AP along muscle fibre and muscle contraction

Question 10

What are examples of drugs that target the central processes of skeletal muscles?

Answer 10

Spasmolytics eg Diazepan and Baclofen

Question 11

What are examples of drugs that target the conduction of nerve AP in motor neurones in skeletal muscles?

Answer 11

Local anaesthetics

Question 12

What are examples of drugs that target ACh release in skeletal muscles?

Answer 12

HEM Ca2+ entry blockers
Icholinium
Neurotoxins

Question 13

What are examples of drugs that target depolarisation of motor end plate and AP initiation

Answer 13

Tubocurarine

Suxamethonium

Question 14

What are examples of drugs that target AP propagation along muscle fibres and muscle contraction?

Answer 14

Spasmolytics eg dantrolene

Question 15

How do postsynaptic NM blocking drugs affect consciousness and pain sensation

Answer 15

These drugs do not affect consciousness or pain sensation

Question 16

What must always be assisted when taking post synaptic NM blocking drugs and give examples of these drugs?

Answer 16

Respiration must be assisted eg taking tubocurarine, atracurium, suxamethonium or succinylcholine

Question 17

What is the method of action of suxamethonium?

Answer 17

It causes a LONG DEPOLARISING BLOCK as it takes a long time to break down in the synaptic cleft and causes FASCICULATIONS then leading to a flaccid paralysis

Question 18

What is a fasciculation?

Answer 18

Brief twitch of muscle fibre

Question 19

How is suxamethonium administered? why is it done like this?

Answer 19

IV (highly charged so IV best way)

Question 20

What is the duration of paralysis of suxamethonium?

Answer 20

Short at approx 5 mins

Question 21

How is suxamethonium metabolised?

Answer 21

By a pseudo-cholinesterase in the liver and plasma

Question 22

What are uses for suxamethonium?

Answer 22

Intubation to relax vocal chords and as a muscle relaxant for electroconvulsive therapy

Question 23

What are unwanted effects of suxamethonium?

Answer 23

Post op muscle pains
Bradycardia due to direct muscarinic action to the heart
Hyperkalaemia
Increase in IOP (therefore dont give to glaucoma patients)

Question 24

What is the method of action of tubocurarine?

Answer 24

It is a competitive nAChR antagonist that blocks 70-80% of what is necessary to cause skeletal muscle relaxation

Question 25

What are the effects of tubocurarine?

Answer 25

Flaccid paralysis which affects the muscles in a particular order:

1. Extrinsic eye muscles (double vision)
2. Small muscles of the face, limbs and pharynx
3. Respiratory muscles

Question 26

In what order do the muscles recover from the effects of tubocurarine?

Answer 26

In a backwards order to how the muscles are effected so the resp muscles recover first and eye muscles recover last

Question 27

What are the clinical uses of tubocurarine?

Answer 27

Relaxation of skeletal muscles during surgical operations

Permits artificial ventilation as it relaxes the resp muscles

Question 28

How can the effects of non depolarising NM blockers be reversed?

Answer 28

Using anticholinesterases eg neostigmine

Question 29

How is tubocurarine administered? Why is it administered this way

Answer 29

Via IV as highly charged

Question 30

How long does the paralysis from tubocurarine last?

Answer 30

A long time approx 40-60 mins

Question 31

How is tubocurarine removed from the body?

Answer 31

It is not metabolised but excreted via urine and bile

Question 32

Why can atracurium be used in patients with renal or hepatic impairment and how long does it last?

Answer 32

It is chemically unstable and lasts 15 mins

Question 33

What are the unwanted effects of tubocurarine?

Answer 33

Causes a ganglion block and histamine release leading to:
Hypotension
Tachycardia
Bronchospasms
Excessive secretions
Apnoea

Question 34

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

1. initial muscle fasciculations
2. irreversible nAChR blockade
3. The block would be enhanced by anticholinesterase drugs
4. Flaccid paralysis
5. Increased arterial pressure

Answer 34

4

Question 35

The clinical use of NM blocking drugs will must likely involve interference with which of the following physiological processes?

1. kidney function
2. conciousness
3. body temperature regulation
4. pain sensation
5. respiration

Answer 35

5