Neuromuscular Blocking Drugs

Question 1

What happens in NM transmission?

Answer 1

Production of ACh using CAT (choline acetyl esterase) -> AP propagation -> Ca2+ influx -> ACh excytosis -> ACh binds to type 1 receptors lading to Na+ influx -> ACh esterase breaks down ACh -> recycling by uptake

Question 2

What are the subunits in the Nicotinic ACh receptor?

Which ones does ACh bind to?

Answer 2

Alpha 1
Alpha 2 
Beta
Delta
Gamma

ACh only binds to alpha receptors

Question 3

Where is there a high density of nicotinic ACh receptors?

Answer 3

Motor-end plate

Question 4

What are the different sites of action of skeletal muscle relaxants?

Answer 4

Spasmolytics e.g diazepam/ baclofen

• target central processes within nerve cell
• spasmlytics relies spasm of muscle

Local anaesthetics
- inhibit influx if sodium so reduce propagation of AP along nerve

Hemicolinium e.g calcium entry blockers/neurotoxins
- inhibit re-uptake of choline

Tubocurarine/suxamethonium
- react on post-synaptic membrane

Question 5

Wha are the different types of post-synaptic NM-blocking drugs?

Answer 5

Non-depolarising (competitive antagonists)

• tubocurarine
• atracurium

Depolarising (agonists) - cause depolarising block
- suxamthonium/succinylcholine(good at stimulating du to very similar structure to ACh

Drugs don’t affect consciousness or pain sensation

Question 6

What are the features of suxamethonium?

Answer 6

Method of action:

• causes long depolarising block (long time to brea down)
• also cause fasciculation (brief twitches f muscle fibre) -> flacid paralysis

Pharmacokinetics:

• administration = IV
• duration of paralysis is short
• metabolised by pseudo-cholinesterase in liver and plasma

Uses:

• intubation (relaxes vocal chords)
• muscle relaxant for electroconvulsive therapy (ECT)

Unwanted effects:

• post-op muscle pains
• bradycardia (direct muscat is action on heart)
• hyperkalaemia (soft tissue injuries or burns -> ventricular arrhythmia/MI)
• increase in IOP (avoid in glaucoma patients)

Question 7

What are the features of tubocurarine?`

Answer 7

Method of action:

• competitive nAChr antagonist
• block of 70-80% necessary to cause effect of muscle relaxation

Effects:

• flacid paralysis then affects muscle in particular order
  1. Extrinsic eye muscle (double vision)
  2. Small muscles of face, limbs and pharunx
  3. Respiratory muscles
• recovery works backwards (eyes recover last)

Uses:

• relaxation of skeletal muscles during surgical operations (less anaesthetic needed)
• permitsartificial ventilation (relaxes resp. Muscles)

Pharmacokinetics:

• Administered via IV (highly charged)
• dosn’t cross BBB/placenta (can be used in pregnant women)
• long term paralysis
• not metabolised - excreted -> 705 urine, 30% bile (care needed if renal/hectic function is impaired)

Unwanted effects:
- causes ganglion block and histamine release
> hypotension (ganglion blockade lowers TPR and histamine release causes vasodilation)
> tachycardia (reflex tachycardia [hypotension] and also due to blockade of a vagal ganglia)
> broncospasm, excessive secretions (histamine release causing bronchoconstriction)
> apnoea (always assist repition)

**effects can be reversed using anticholinesterases e.g neostigmie)