PHAR232 - Neuromuscular blockers Flashcards
Are neuromuscular blockers depolarising or non-depolarising? (located at neuromuscular junction)
Both - working on nAChRs
NO TONE
WET NOODLE
What are non-depolarising blockers?
nicotinic antagonists
What are depolarising blockers?
Nicotinic agonists
What was the first non-depolarising neuromuscular blocker?
Curare
‘kur-rah-ree
What is the active compound for morphine and codeine?
Alkaloids
What is the suffix associated with curarine or tubocurarine?
Things ending in curonium or curium
Non-depolarising NM blockers - KNOW THIS
Can non-depolarising neuromuscular blockers be overcome?
Yes - as they are agonist or competitive antagonists
e.g. acetylcholinesterase INHIBITOR to encourage ACh release to outcompete NM blocker
AChE inhibitor information
KNOW HOW AChE WORKS (antidote)
Tries to not let it get systemic for PSNS for side effects etc
PNS
- Tears
- Brochodilation
- Uncontrolable bladder
- Salivation etc
Is 4-aminopyridine an AChE inhibitor ?
No
It OUTCOMPETES NM blocker to ACTIVATE nAChRs on muscle cells
Is 4-aminopyridine a longer or shorter-acting?
Longer
Does 4-aminopyridine cross the BBB?
Yes
What do non-depolarising NM blockers tubocurarine, mivacurium, atracurium all have in common?
Induce histamine release
What can a significant histamine release induce?
Drop in BP
Cause bronchospasms
REVIEW AND UPDATE =- PRINT OUT ALL OF THE DIAGRAMS IN THE TEXT BOOK
are depolarising NM blockers agonists or antagonists?
They are nAChR agonists = they depolarise
What is the only clinically relevant compound for depolarising NM blockers for humans?
Suxamethonium (succinylcholine)
How long does suxamethonium aka succinylcholine have after depolarisation for desensitization?
30 sec desensitation
How does a depolarising NM blocker work e.g. suxamethonium for phase 1?
Continuous nicotinic ACh receptor depolarisation is overstimulated
- Prevents repolarisation
- Short acting paralysis (phase 1)
How does a depolarising NM blocker work e.g. suxamethonium for phase 2?
phase 2
- Repeated exposure = increased accumulation of metabolite SUCCINYLMONOCHOLINE
- Succinylmonocholine = antagonist curare action
= PHASE II blocker
CONTINUES as an antagonist and blocks NM nAChRs
Is phase II of depolarising NM blockers and non-DNM blockers the same actions?
yes - know the steps they are the same
What do all neuromuscular blockers paralyse?
Skeletal muscle
Are respiratory muscles under skeletal muscles?
Yes
Do all neuromuscular blockers cause respiratory paralysis?
Yes
What is the main target for muscle relaxants?
GABA
What does baclofen target as a muscle relaxant?
A GABA-B agonist
Learn GABA-B receptor signalling = for baclofen
MECHANISM OF ACTION FOR BACLOFEN
PKA is _________ dependent
cAMP dependent
What happens if you inhibit AdCy?
- decrease cAMP
- Decrease PKA
- Decrease VG-Ca2+ channels
- Decrease synaptic vesicle mobilisation
- Decrease NT release
Baclofen post-synaptic mechanism of action
Baclofen antispasmotic effect is mainly exerted through _________
Spinal cord
What does the activation of GABA-B receptors do post-synaptically?
- Activate inward K+ channels
- Increase efflux of K+
- Hyperpolarise post-synaptic motor neurons
Benzodiazepam therapeutic interventions
Benzodiazepines are ________________ modulators
positive allosteric modulator
What is a positive allosteric modulator?
Its easier to GABA to activate its own receptor
mehcniams of action of benzodiazepines (BDZ)
MECHANISM OF ACTION FOR DANTROLENE
Dantrolene is a _____________ and _____________ antagonist
Ryanodine receptor 1 (RyR1)
Ryanodine receptor 3 (RyR3)
What does dentrolene primarily act on?
Skeletal muscle receptors RyR1
Are RyR3 receptors found in the brain?
Yes
What is a ryanodine receptor channel pathway?
Ryanodine receptors are part of a channl to promote Ca2+ efflux from the SR in the cytoplasm
