PHAR232 - Neuromuscular blockers

Question 1

Are neuromuscular blockers depolarising or non-depolarising? (located at neuromuscular junction)

Answer 1

Both - working on nAChRs

NO TONE
WET NOODLE

Question 2

What are non-depolarising blockers?

Answer 2

nicotinic antagonists

Question 3

What are depolarising blockers?

Answer 3

Nicotinic agonists

Question 4

What was the first non-depolarising neuromuscular blocker?

Answer 4

Curare

‘kur-rah-ree

Question 5

What is the active compound for morphine and codeine?

Answer 5

Alkaloids

Question 6

What is the suffix associated with curarine or tubocurarine?

Answer 6

Things ending in curonium or curium

Question 7

Non-depolarising NM blockers - KNOW THIS

Answer 7

Question 8

Can non-depolarising neuromuscular blockers be overcome?

Answer 8

Yes - as they are agonist or competitive antagonists

e.g. acetylcholinesterase INHIBITOR to encourage ACh release to outcompete NM blocker

Question 9

AChE inhibitor information

Answer 9

KNOW HOW AChE WORKS (antidote)

Question 10

Tries to not let it get systemic for PSNS for side effects etc

Answer 10

PNS
- Tears
- Brochodilation
- Uncontrolable bladder
- Salivation etc

Question 11

Is 4-aminopyridine an AChE inhibitor ?

Answer 11

No
It OUTCOMPETES NM blocker to ACTIVATE nAChRs on muscle cells

Question 12

Is 4-aminopyridine a longer or shorter-acting?

Answer 12

Longer

Question 13

Does 4-aminopyridine cross the BBB?

Answer 13

Yes

Question 14

What do non-depolarising NM blockers tubocurarine, mivacurium, atracurium all have in common?

Answer 14

Induce histamine release

Question 15

What can a significant histamine release induce?

Answer 15

Drop in BP
Cause bronchospasms

Question 16

REVIEW AND UPDATE =- PRINT OUT ALL OF THE DIAGRAMS IN THE TEXT BOOK

Question 17

are depolarising NM blockers agonists or antagonists?

Answer 17

They are nAChR agonists = they depolarise

Question 18

What is the only clinically relevant compound for depolarising NM blockers for humans?

Answer 18

Suxamethonium (succinylcholine)

Question 19

How long does suxamethonium aka succinylcholine have after depolarisation for desensitization?

Answer 19

30 sec desensitation

Question 20

How does a depolarising NM blocker work e.g. suxamethonium for phase 1?

Answer 20

Continuous nicotinic ACh receptor depolarisation is overstimulated
- Prevents repolarisation
- Short acting paralysis (phase 1)

Question 21

How does a depolarising NM blocker work e.g. suxamethonium for phase 2?

Answer 21

phase 2

• Repeated exposure = increased accumulation of metabolite SUCCINYLMONOCHOLINE
• Succinylmonocholine = antagonist curare action
  = PHASE II blocker

CONTINUES as an antagonist and blocks NM nAChRs

Question 22

Is phase II of depolarising NM blockers and non-DNM blockers the same actions?

Answer 22

yes - know the steps they are the same

Question 23

Answer 23

Question 24

Question 25

What do all neuromuscular blockers paralyse?

Answer 25

Skeletal muscle

Question 26

Are respiratory muscles under skeletal muscles?

Answer 26

Yes

Question 27

Do all neuromuscular blockers cause respiratory paralysis?

Answer 27

Yes

Question 28

What is the main target for muscle relaxants?

Answer 28

GABA

Question 29

What does baclofen target as a muscle relaxant?

Answer 29

A GABA-B agonist

Question 30

Learn GABA-B receptor signalling = for baclofen

Answer 30

MECHANISM OF ACTION FOR BACLOFEN

Question 31

PKA is _________ dependent

Answer 31

cAMP dependent

Question 32

What happens if you inhibit AdCy?

Answer 32

- decrease cAMP - Decrease PKA - Decrease VG-Ca2+ channels - Decrease synaptic vesicle mobilisation - Decrease NT release

Question 33

Baclofen post-synaptic mechanism of action

Question 34

Baclofen antispasmotic effect is mainly exerted through _________

Answer 34

Spinal cord

Question 35

What does the activation of GABA-B receptors do post-synaptically?

Answer 35

- Activate inward K+ channels - Increase efflux of K+ - Hyperpolarise post-synaptic motor neurons

Question 36

Benzodiazepam therapeutic interventions

Question 37

Benzodiazepines are ________________ modulators

Answer 37

positive allosteric modulator

Question 38

What is a positive allosteric modulator?

Answer 38

Its easier to GABA to activate its own receptor

Question 39

mehcniams of action of benzodiazepines (BDZ)

Question 40

MECHANISM OF ACTION FOR DANTROLENE

Question 41

Dantrolene is a _____________ and _____________ antagonist

Answer 41

Ryanodine receptor 1 (RyR1) Ryanodine receptor 3 (RyR3)

Question 42

What does dentrolene primarily act on?

Answer 42

Skeletal muscle receptors RyR1

Question 43

Are RyR3 receptors found in the brain?

Answer 43

Yes

Question 44

What is a ryanodine receptor channel pathway?

Answer 44

Ryanodine receptors are part of a channl to promote Ca2+ efflux from the SR in the cytoplasm