Pharm 10 - NMJ blocking drugs

Question 1

Somatic motor nervous system uses which neurotransmitter?

Answer 1

ACh. Only a single axon

Question 2

What enzyme is used for ACh synthesis?

Answer 2

CAT (cholinoacetyl transferase)

Question 3

Muscle type NAChR are different to ganglionic NAChR?

Answer 3

True

Question 4

ACh binds to the alpha subunits of the NAChR. Typically how many ACh must bind to the NAChR for it to open?

Answer 4

2

Question 5

Baclofen is a spasmolytic. It is a —— agonist

Answer 5

GABA

Question 6

What do local anaesthetics act on?

Answer 6

VGSC

Question 7

Dantrolene is a spasmolytic. Where does it work and what is its mode of action?

Answer 7

Inhibits release of Ca from Sarcoplasmic reticulum stores - less powerful muscle contraction

Question 8

What are the sites of action of drug action?

Answer 8

1. Central processes
2. Conduction of AP along motor neurone
3. ACh release
4. Depolarisation of motor end plate - AP initiation
5. Propagation of AP along muscle fibre + muscle contraction

Question 9

What drugs can be used to target central processes?

Answer 9

Spasmolytics - e.g. diazepam or Baclofen

Question 10

What drugs can be used to target the conduction of AP along motor neurone?

Answer 10

Local anaesthetics

Question 11

What drugs can be used to target ACh release?

Answer 11

1. Ca entry blockers
2. Neurotoxins (e.g. botulinum)
3. Hemicholinium

Question 12

What drugs can be used to target depolarisation of motor end plate ?

Answer 12

1. Tubocurarine

2. Suxamethonium

Question 13

What drugs can be used to inhibit propagation of the AP along muscle fibre?

Answer 13

Certain spasmolytics e.g. Dantrolene

Question 14

Do neuromuscular blocking drugs work presynaptically or postsynaptically?

Answer 14

Postsynaptically

Question 15

What are the 2 classes of neuromuscular blocking drug that work postsynaptically?

Answer 15

1. Non-depolarising (competitive antagonists)

2. Depolarising (agonists)

Question 16

Give an example of a non-depolarising NM blocking drug?

Answer 16

Tubocurarine

Atracurium

Question 17

Give an example of a depolarising NM blocking drug

Answer 17

Suxamethonium

Question 18

Do NM blocking drugs affect consciousness or pain sensation?

Answer 18

No

Question 19

What must always be assisted when giving NM blocking drugs in surgery?

Answer 19

Respiration

Question 20

What is the mode of action of suxamethonium?

Answer 20

Excessively stimulates NAchR on end plate - causing extended depolarisation. Suxamethonium takes 5/6 minutes to leave the synaptic cleft

This causes “depolarisation block” (aka Phase 1 block)

Question 21

What other drug can also cause depolarising block?

Answer 21

Ecothiopate

Question 22

What can happen in the first few minutes after administering suxamethonium?

Answer 22

Fasciculations - muscle twitches

Flaccid paralysis may follow - loss of tone in SkM

Question 23

How is suxamethonium administered?

Answer 23

Intravenously

Question 24

What is the duration of paralysis with suxamethonium?

Answer 24

5 minutes (SHORT)

Question 25

What is suxamethonium metabolised by?

Answer 25

Pseudo-cholinesterase

Question 26

Name 2 uses of suxamethonium

Answer 26

1. Endotracheal intubation | 2. Muscle relaxant for ECT

Question 27

What are some unwanted effects of suxamethonium?

Answer 27

1. Post-op muscle pains 2. Bradycardia due to direct muscarinic action on the heart (M2 receptors) but this is usually solved by coadministration of atropine 3. Hyperkalaemia - e.g. giving patients with soft tissue damage/burns patients is very dangerous - causes greater sodium influx and greater K efflux 4. Increased intraocular pressure - avoid for patients with eye injuries or glaucoma

Question 28

Why is it dangerous to give burns patients/soft tissue damage patients suxamethonium?

Answer 28

De-innervation up regulation of NAChR on SkM

Question 29

What can hyperkalaemia cause (in worst case scenarios)?

Answer 29

Ventricular arrhythmias and cardiac arrest

Question 30

What is a naturally occurring 4 Ammonium compound (alkaloid) found in S.American plants?

Answer 30

Tubocurarine

Question 31

What is the mode of action of tubocurarine?

Answer 31

Competitive NAChR antagonist - competes with endogenous ACh

Question 32

What % block is needed from tubocurarine to prevent the End plate potential firing an AP?

Answer 32

70-80% BLOCK

Question 33

What are the effects of tubocurarine?

Answer 33

Flaccid paralysis 1. Initially, extrinsic eye muscles relax (double vision) 2. Then small muscles of face, limbs, pharynx 3. Then, respiratory muscles

Question 34

What is tubocurarine used for?

Answer 34

1. SkM relaxation for surgery (means less General anaesthetic is needed) 2. Relaxes respiratory muscles, allows artificial ventilation

Question 35

What can non-depolarising blockers be reversed by?

Answer 35

Anticholinesterases (e.g. Neostigmine (+ Atropine))

Question 36

How is tubocurarine given?

Answer 36

IV

Question 37

Tubocurarine is not very lipid soluble so it doesn't cross which 2 things?

Answer 37

BBB or placenta

Question 38

What is the duration of paralysis with tubocurarine?

Answer 38

1-2 hours

Question 39

Is tubocurarine metabolised?

Answer 39

No, it is excreted (70% urine, 30% bile)

Question 40

If there are renal/hepatic problems in the patient, you don't give tubocurarine. What do you give instead?

Answer 40

Atracurium (15 mins DOA) - DOA not determined by liver or kidney function.

Question 41

What are the unwanted effects of giving tubocurarine?

Answer 41

1. Ganglion block and histamine release 2. Hypotension due to Ganglion block (TPR decrease) and histamine release (H1 receptor causing vasodilation) 3. Tachycardia - reflex tachycardia or blockade of vagal ganglia 4. Bronchospasm and excessive secretions (histamine release) 5. Apnoea (always assist respiration)

Question 42

What can basic drugs do to mast cells?

Answer 42

Cause them to release histamines