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Pharm > Neuromuscular blocking drugs > Flashcards

Neuromuscular blocking drugs Flashcards

1
Q

How does excitation differ in post synaptic membrane in muscle vs ganglionic

A

Differenct nAChR for muscle vs ganglionic nAChR…..

these are muscle type nicotinic receptors, different to ganglionic neurone nicotinic recepor (so some selectivity can be developed)

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2
Q

What nervous system do NM blocking drugs affect

A

Somatic NS –> alpha motor neurons coming from the spinal cord….

A single axon innervating skeletal muscle fibres

Cholinergic

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3
Q

How is acetylcholine made

A

Acetyl CoA + choline

by cholineacetyl transferase (CAT)

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4
Q

Where else is cholineacetyl transferase found in the body other than cholinergic neurons

A

Nowhere else

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5
Q

What type of receptor is present on muscle fibre

A

Nicotinic Acetylcoline receptor…..

It is a cation channel (most sodium influx but also escape of K+ and small amount of Ca2+ comes in too)

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6
Q

What is the name of the depolarisation in the post synaptic membrane

A

The end plate potential

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7
Q

Differentiate end plate potential to action potential

A

End plate potential is graded (dependent on concentration of nicotinic receptor and amount of ACh),

AP is all or nothing

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8
Q

Where is the highest concentration of nicotinic receptors in skeletal muscle

A

Centre of the muscle

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9
Q

How is acetylcholine broken down

A

by acetylcholineesterase…. into acetic acid and choline…..
Choline taken back up by transporter in presynaptic membrane

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10
Q

State the 2 types of NM blocking drugs

A

Competitive antagonist (non depolarising)

Depolarising blockers (AGONISTS of nAChR)

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11
Q

How many subunits in the type 1 receptors

A

5

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12
Q

Where does acetylcholine bind to the receptors

A

Onto the TWO alpha subunits of the nicotinc receptor

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13
Q

Differentiate the composition of muscle type and ganglion type nicotinc receptors

A

Muscle type: 2a b d e
Ganglion: 2a, 3b

Note that each subunit is comprised of 4 TM segments
Also note that there are 5 potential subunits: a, b, d, e and g

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14
Q

Example of drugs that work on central processes to reduce outflow from CNS to affect muscle

A

SPASMOLYTICS (diazepam and baclofen) they reduce outflw from CNS to allow relaxation in spasticity e.g. due to MS

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15
Q

Example of drug affecting conduction of nerve AP in motor neurone to affect muscle

A

Local anaesthetic (meant to block action potential in sensory fibres, but can also affect motor)

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16
Q

Which drugs can affect ACh release from the presynaptic neuron to affect muscle

A

Ca2+ entry blockers (required to release NT)

Neurotoxins (e.g. venom) can cause paralysis e.g. botulinum toxin which prevents release ACh release from presynaptic cell

Hemicholinim (stops reuptake of choline to reduce ACh synthesis and thus release form the presynaptic membrane)

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17
Q

What drugs affect DEPOLARISATION OF MOTOR END-PLATE causing AP INITIATION to affect muscle

A

TUBOCURARINE

SUXAMETHONIUM

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18
Q

What drugs affect PROPAGATION OF AP ALONG MUSCLE FIBRE + MUSCLE CONTRACTION to affect muscle

A

Spasmolytic dantrolene (reduces release of Ca2+ from the SR reducing propogation)

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19
Q

Where is the action of NM blockin drugs

A

POST synaptic….. end place receptors

20
Q

Give an example of each type of NM blocking drug

A

Competitive antagonist (non depolarising) –> tubocuarine and atracurium

Depolarising blockers (AGONISTS of nAChR) –> suxamethonium (=succinylcholine)

21
Q

What is done when NM blocking drugs are used

A

Assist respiration

22
Q

Differentiate chemical structure of competitve antagonists vs depolarising blockers

A

Ach has quarternary ntirogen

The suxamethonium basically 2 molecules of ACh stuck together. It has 2 quartnery nitrogens, so it can stimulate both of the a subunits at the same time this increases efficacy. There is efficacy and affinity for ACh receptor (agonist)

competitve antagonists have more rigid structures than depolarising blockers with less rotation about the double bond. Tubocuranine still has quarternary nitrogen but only has affinity and no efficiacy for the receptor

23
Q

What is the strucutre of the succinylcholine (=suxamethonium)

A

Basically 2 acetylcholines stuck together (so they have efficacy and affinity)

24
Q

MOA of depolarising blocker

A

Overstimulation of the nicotinic receptor suxamethonium stays in the synaptic cleft for a long period of time, rather than rapid removal like ACh

EXTENDED E.P. DEPOLARISATION –> ‘DEPOLARISATION BLOCK’ (PHASE 1)

FASCICULATIONS –> FLACCID PARALYSIS (loss of tone , compared with spastic paralysis) (as it stimulates individual fibres as it diffuses through)

25
Q

State the suxamethonium pharmacokinetics

A

IV (highly charged due to two quarternary nitrogens)

Duration of paralysis is 5 minutes (SHORT)

METABOLISED BY PSEUDO-CHOLINESTERASE IN LIVER & PLASMA

26
Q

Uses of suxamethonium

A

Both Es and both brutal

Endotracheal intubation –> to relax muscle to intubate for investigation

Muscle relaxant for ECT –> electoconvulsive therapy involves stimuation across temporal lobes…. it prevents muscle contraction during this treatment of sever depression

27
Q

Unwanted effects of suxamethonium

A

POST-OPERATIVE MUSCLE PAINS

BRADYCARDIA

HYPERKALAEMIA…

INCREASE INTRA-OCULAR PRESSURE

I Hurt P Bum

28
Q

How do non-depolarsing NM blocker work

A

NATURALLY OCCURING 4° AMMONIUM COMPOUND (ALKALOID) e.g. tubacuranine

Competitive nAChR anagonist

(all non deplarising NM blocking drugs use same mechanism)

(there is a quarternary nitrogen group like ACh so binding to the receptor can occur but there is no efficacy

29
Q

What block is achieved in non-depolarising NM blockers

A

70 - 80% BLOCK NECESSARY… in this case you don’t get a suffieicnet end plate potential to reach an action potential

30
Q

Effets of non depolarising NM blockers, and which muscles are blocked at low to high dosage

A

Flaccid paralysis

Extrinsic eye muscle (double vision) 
THEN 
Small muscle of face limbs and pharynx 
THEN 
respiratory muscles

(RECOVER IN OPPOSITE DIRECTION)

31
Q

Eplain why in number 3 on the tubocurarine is there an action potential but nothing further down the muscle fibre

A

The endplate potneital is not sufficient to cause action potential (which is all or nothing) so there is no depolarisation

32
Q

Use of non-depolarising NM blocker

A

RELAXATION OF SKELETAL MUSCLES DURING SURGICAL OPERATIONS (= LESS ANAESTHETIC) incl. abdominal muscle… use less general anaesthetic because although GA causes relaxation too, we can use less GA if we use muscle relaxant

PERMIT ARTIFICIAL VENTILATION

33
Q

How can the action of non-repolarising blockers be reversed

A

ACTIONS OF NON-DEPOLARISING BLOCKERS CAN BE REVERSED BY ANTICHOLINESTERASES
e.g. neostigmine AND atropine (to block the increased effect at the muscarinic receptors)

34
Q

Pharmacokinetics of tubocurarine

A

IV
Does not cross BBB or placenta (due to quarternary ammonium)
Paralysis is 1-2hrs (long)
Not metabolised
Excreted 70% in urine and 30% in the bile

35
Q

When might we not use tubacuranine? What is used instead

A

If renal or hepatic function is impaired, because this will EXTEND the duration of action of this drug.

In this case, we give atracurium which is chemically unstable (and is hydrolysed in the plasma into 2 inactive components spontaneously, not dependent on renal or kidney function for its DOA)

Compare to tubacurarine which is excreted UNmetabolised.

36
Q

What are the unwanted effects of tubocurarine

A

Due to 1. Ganglion block and 2. Histamine release:

BATH

Bronchospasm and excessive secretions due to HISTAMINE RELEASE

Apnoea- due to blockade of respiratory muscles (so assist respiration)

Tachycardia- block of vagal ganglia and reflex tachycardia due to vasodilation may lead to arrhythmias

Hypotension –> reduction in TPR because of block of ganglionic nAChR + histamine from mast cells

37
Q

Why does suxamethonium cause muscle pain post operatively

A

Due to the fasciculations (make sure you know why fasciaulations occur)

38
Q

Why does suxamethonium cause bradycardia. What is the solution

A

suxamethonium also stimulates M2 receptors on the heart…. but atropine include in pre-medication. Atropine BLOCKS the muscarinic receptor

39
Q

Why does suxamethonium cuase hyperkalaemia. When would you not use suxamethonium and why

A

It increases NAChR stimulating (as it is an agonist), increasing sodium influx and potassium efflux (then it causes depolarisation block)

WOULD NOT USE in burns patients or other soft tissue injury, as here denervation happens, so receptors become more sensitive (denervation hypersensitivity), so more potassium is released. Can lead to ventricular arrhythmias and cardiac arrest.

40
Q

When else would you not use suxamethonium

A

Burns or glaucoma/eye injury

41
Q

Why does suxamethonium cause raised intraocular pressure

A

due to contraction of skeletal muscle around the eye…. avoid for glaucoma and eye injuries

42
Q

Outline 2 drug groups which cause depolarisation block

A

Suxamethonium is an agonist and isn’t broken down by acetylcholinestease so remain so in the synapse causing the phase 1 block

Ecothiopate is an organophosphate and is a irreversible indirectly acting cholimomimitetic (ie irreversibly inhibits acetylcholinesterase) which causes build up of ACh in the synapse and also causes depolarising block

43
Q

Tubocurarine is given in surgery as a muscle relaxant to permit easier surgery. Once the operation is complete, what could then be given to reverse the effect of this drug

A

It is a NM blocking drug, so it is working on the ACh receptors.

It is REVERSIBLE, so it can be surmounted. If you use a reversible anticholinesterase e.g Neostigmine.

However giving neostigmine could increase transmission at muscarinic receptors, so atropine is given to block any of these effects

44
Q

Which NM blocker is long acting and which is short

A

Long: tubacurarine

Short: suxamethonium

45
Q

T/f tubocurarine can be used during obstetric surgery

A

T…. it cannot cross the placenta or the BBB as it is very highly charged

46
Q

Why does tubocurarine cause histamine release

A

Because it is a base, it can cause histamine release from mast cells (not a receptor mediated effect)

Pharm (33 decks)

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