Pharm 10 - Neuromuscular Blocking Drugs Flashcards
Describe how impulses are transmitted across synapses.
Action potential propagates along the presynaptic neurone –> depolarisation of presynaptic membrane –> oprening of VGCC –> calcium influx –> vesicle exocytosis
What type of receptor is found at the neuromuscular junction?
nicotinic acetycholine receptors
Where are these receptors found on the muscle fibre?
Motor end plate
What does depolarisation of the motor end plate cause?
Causes a change in end plate potential
Graded potential
Once it reaches its threshold, action potential propagates in both directions away
Where is acetylcholinesterase found?
bound to basement membrane in the synaptic cleft
State the three main neuromuscular blockers.
Tubocurarine
Atracurium
Suxamethonium
State the two main types of nicotinic acetylcholine receptor.
Ganglionic
Muscle
Describe the structure of nicotinic acetylcholine receptors.
5 subunits
How many molecules of acetycholine are required to activate 1 nicotinic acetylcholine receptor?
2
Name 2 drugs that are used as spasmolytics.
Diazepam
Baclofen
Both help GABA transmission
GABA is inhibitory so reduce epilepsy etc
Give some examples of conditions in which spasmolytics may be used
cerebral palsy and spasticity
What do local anaesthetics have their effect on?
Conduction of action potentials in motor neurones
Describe the action of neurotoxins.
inhibit the release of acetylcholine and hence block the contraction of respiratory skeletal muscle causing death
Describe the difference between depolarising and non-depolarising NM blockers.
depolarising = suxamethonium = nicotinic acetylcholine receptor agonist
non-depolarising = tubocurarine + atracurium = nicotinic acetylcholine receptor antagonist
How do NM blockers affect conciousness and pain?
They DO NOT
What must you always do when giving NM blockers?
assist respiration
Describe the difference in structure between non-depolarising and depolarising NM blockers.
Non-depolarising = big, bulky molecules with limited movement around
their bonds
Suxamethonium = made up of two acetylcholine molecules that are
linked together. This is more flexible and allows rotation. As it is made
up of two acetylcholine molecules it can binds to the two alpha subunits
and activate the receptor.
Describe the mechanism of action of suxamethonium.
agonist
extended end plate depolarisation leading to depolarising block of the NMJ
What does Suxamethonium normally cause before causing the flaccid paralysis?
Fasciculations
What is the duration of paralysis of suxamethonium?
5 mins
How is suxamethonium metabolised?
by pseudocholinesterase in liver and plasma
What are some uses of suxamethonium?
Endotracheal intubation
Muscle relaxant
State 4 unwanted effects of suxamethonium.
1) Post surgical muscle pain because of fasciculations
2) hyperkalaemia
3) bradycardia
4) raised intraocular pressure
Describe the mechanism of action of tubocurarine.
competitive nicotinic acetylcholine receptor antagonist
need to block around 70-80% of receptors
State the order of relaxation of skeletal muscles when administering tubocurarine.
- extrinsic eye muscles
- small muscles of face limbs and pharynx
- resp muscles
State 2 uses of tubocurarine.
relaxation of muscles during surgical operations
permit artifical ventilation
How can the actions of NM blockers be reversed?
Give a anti-cholinesterase
What else would you give with an anticholinesterase?
atropine to stop some unwanted side effects
How are NM blockers administered?
iv
What is the duration of action of tubocurarine?
40 mins
Under which conditions would you get increased duration of tubocurarine?
Impaired renal or hepatic functions
What are the main unwanted effects of tubocurarine?
- hypotension
- tachycardia
- bronchospasm
- excessive secretions
- apnoea
