Pharmacology

Question 1

3 ways to block neuromuscular transmission:

Answer 1

Presynaptically - inhibiting ACh synthesis or release

Postsynaptically

Question 2

How can you block neuromuscular transmission presynaptically through inhibiting ACh SYNTHESIS?

Answer 2

Block rate-limiting step of choline uptake

Question 3

How can you block neuromuscular transmission presynaptically through inhibiting ACh RELEASE?

Answer 3

Not much specificity

Question 4

How can you block neuromuscular transmission postsynaptically?

Answer 4

Interfering with actions of ACh on receptor - more specific

Question 5

What can you use to inhibit ACh release?

Answer 5

Local anaesthetics

General inhalation also anaesthetics

Inhibitors/competitors of calcium

Neurotoxins

Question 6

Examples of Inhibitors/competitors of calcium:

Answer 6

Magnesium ions

Some antibiotics

Question 7

Some examples of Neurotoxins:

Answer 7

Botulinum toxin

Question 8

What does BOTOX stand for?

Answer 8

Botulinum toxin - relaxes muscles underneath skin

Question 9

Clinical uses of neuromuscular blocking drugs:

Answer 9

Endotracheal intubation

During surgical procedures

Intensive care

During electroconvulsive therapy

Question 10

Structure of Nicotinic acetylcholine receptor:

Answer 10

Pore in centre

5x subunits

2 binding regions for ACh

Question 11

Types of blockers for Nicotinic ACh receptors:

Answer 11

Agonists - depolarising

Antagonists - non-depolarising

Question 12

Why are agonist drugs depolarising?

Answer 12

Stimulate pore opening

Question 13

Why are antagonists non-depolarising?

Answer 13

Prevent ACh binding - pore remains closed

Question 14

Examples of competitive non-depolarising antagonist blockers:

Answer 14

Tubocuraine

Atracurium

Question 15

How do antagonists result in no activation of muscle action potential?

Answer 15

Prevent ACh binding by occupying site

Decrease motor end plate potential

Decreases depolarisation of motor end plate region

Question 16

Example of depolarising agonist blocker:

Answer 16

Suxamethonium

Question 17

How do agonists over-stimulate the cell?

Answer 17

Not metabolised by Acetylcholine esterase- prolongs activity of ACh at neuromuscular junction

Question 18

How do depolarising agonist blockers result in no more action potentials being generated?

Answer 18

Persistent depolarisation of motor end plate and muscle membrane

Prolonged end plate potential

Question 19

What does the prolonged depolarisation of muscle membrane caused by depolarising agonists result in?

Answer 19

Membrane potential above threshold for resetting voltage-gated sodium channels

Channels remain refractory - can’t reset

Question 20

Phase 1 of depolarising block:

Answer 20

Muscle fasciculatations, then blocked

Repolarisation inhibited

Sodium channels remain inactivated

Question 21

Phase 2 of depolarising block:

Answer 21

Desensitisation blockade - no depolarisation as receptors are refractory

Question 22

Examples of non-depolarising blockers:

Answer 22

PARVM

P = Pancuronium (SE Tachycardia)

A = Atracurium (SE hypotension)

R = Rocuronium (SE Tachycardia)

V = Vecuronium (SE few)

M = Mivacurium (SE hypotension)

Question 23

Side effects of Suxamethonium:

Answer 23

Bradycardia

Question 24

Ways of degrading Atracurium:

Answer 24

Ester hydrolysis and Hofmann elimination

Rapid degradation

Question 25

Ways to degrade Mivacurium:

Answer 25

Plasma cholinesterases

Question 26

Ways to degrade suxamethonium:

Answer 26

Plasma cholinesterases

Question 27

Ways to degrade Pancuronium:

Answer 27

Hepatic metabolism Slow - longer duration of immobility

Question 28

Ways to degrade Vecuronium:

Answer 28

Hepatic metabolism Slow - longer duration of immobility

Question 29

Ways to degrade Recuronium:

Answer 29

Unchanged in bile/urine

Question 30

What do cholinesterases degrade?

Answer 30

Mivacurium Suxamethonium

Question 31

Types of cholinesterases:

Answer 31

Acetylcholinesterase - hydrolysis of ACh Plasma cholinesterases

Question 32

What inhibits cholinesterases enzymes?

Answer 32

Anticholinesterase drugs

Question 33

What do anticholinesterase drugs do?

Answer 33

Increase ACh at neuromuscular junction Decrease degradation - longer duration of ACh Reversible or irreversible effects on enzyme

Question 34

Effects of anticholinesterases:

Answer 34

CNS = convulsions ANS - many effects

Question 35

Effects of anticholinesterases on ANS:

Answer 35

SLUDGE ``` Salivation Lacrimation Urination Defecation GI upset Emesis ```

Question 36

Clinical uses of anticholinesterases:

Answer 36

Anaesthesia Alzheimer’s disease Myasthenia Gravis

Question 37

What is Myasthenia gravis?

Answer 37

Auto-immune reaction Block receptor to ACh -> muscle weakness

Question 38

What reverses effect of rocuronium and Vecuronium?

Answer 38

Selective binding agent