Neuromuscular blocking drugs Flashcards
What is the neurotransmitter at the skeletal NMJ? What receptor type does it act on?
Acetyl choline
Nicotinic acetyl choline receptors on the motor end-plate
What are the clinical uses of neuromuscular blocking agents?
Suxamethonium:
Endotracheal intubation - relaxes airway skeletal muscle
Muscle relaxant for electroconvulsant therapy for severe clinical depression
Tubocurarine:
Relaxation of skeletal muscles during surgery (less anaesthetic needed)
Permit artificial ventilation
What are unwanted effects of tubocurarine?
- Ganglion block
- Histamine release from mast cells
- Hypotension
- Tachycardia –> arrhythmias
- Bronchospasm
- Excessive secretions
- Apnoea - tf assist breathing
How does tubocurarine work?
- Competitive nicotinic AChR antagonist
- Need about 70-80% block to achieve full relaxation of muscles
- If you block enough receptors, EPP generated does not reach threshold
Describe the pharmacokinetics of tubocurarine
- IV
- Does not cross BBB or placenta
- Long duration of paralysis: 40-60 mins
- Not metabolised
- Excreted in urine (70%) and bile (30%)
- Any impairment in hepatic or renal fn increases duration of action
How does tubocurarine alter the log dose-response curve showing the response of skeletal muscle to increasing [ACh]?
Moves curve right without reducing the maximal response to ACh
How long does the paralysis caused by tubocurarine last?
40-60 minutes
Are NM blockers metabolised?
Depolarising - yes
Non-dp - no
Does tubocurarine cross the BBB?
No
Is tubocurarine metabolised?
Not at all
How does any impairment of hepatic or renal function affect the effects of tubocurarine?
Increases their duration of action
What should be coadministered with tubocurarine if there is any impairment of hepatic or renal function?
Atracurium (15 mins duration of action)
Then effects of tubocurarine effects are not affected by lack of liver/kidney function
What is the main effect of NM blockers?
Flaccid paralysis (no muscle tone)
How does suxamethonium work?
- Depolarising
- Nicotinic AChR agonist
- Causes extended end plate DP
- Leads to a depolarisation block of NMJ caused by overstimulation (phase 1 block)
- Isn’t metabolised as rapidly as ACh so remains bound to AChRs - receptors quickly switch off
What are the effects of non-depolarising NM blockers?
Flaccid paralysis (no muscle tone) in particular order (reverse back to normal):
- Extrinsic eye muscles
- Small muscles of face, limbs, pharynx
- Respiratory muscles
- Fasciculations
Does suxamethonium cross the BBB?
No
What are the unwanted effects of suxamethonium?
Post-operative muscle pains - due to initial fasciculations
Bradycardia - direct muscarinic action on heart
Hyperkalaemia - soft tissue injury or burns can lead to ventricular arrhytmias, cardiac arrest
Raised intraocular pressure
How is unwanted bradycardia usually prevented when giving suxamethonium?
Suxamethonium has direct muscarinic action on heart
Suxamethonium is given after GA
Atropine - competitive muscarinic antagonist - given in pre med
What is the target of NM blockers?
Post-synpatic nictonic AChRs on motor end plate
What are the 2 groups of NM blockers with examples?
- Non-depolarising - competitve nicotinic receptor antagonists
E.g. tubocurarine, atracurium - Depolarising - nicotinic receptor agonists
E.g. suxamethonium
Why do you always assist respiration when giving NM blockers?
NM blockers affect respiratory muscles and cause apnoea
Compare the structure of non-depolarising and depolarising NM blockers
Non-depolarising:
Big, bulky molecules
Restricted movement around bonds
DP:
2 ACh molecules linked together
Flexible, allows rotation
What are the pharmacokinetic features of suxamethonium?
- i.v. (highly charged)
- Duration of paralysis = 5 mins
- Metabolised by pseudocholinesterase in liver + plasma
