Neuromuscular Blockers Flashcards
Use of the “oniums?”
- adjunct for general surgery
- helps manage diaphragm, so don’t have to use as much anesthetic
Difference between nicotinic and muscarinic acetylcholine receptors?
- nicotinic is comprised of multiple subunits
- ligand gated ion channel
- two alpha subunits need to be bound by acetylcholine to activate it
Role of skeletal muscle blocking drugs?
- block effects of ACh at nicotinic muscle receptors (Nm)
- used during surgery for paralysis of muscles (diaphragm)
Nondepolarizing blockers?
- antagonist
- competitive inhibitor of ACh
- prevents ACh from interacting and keeps gate closed
Depolarizing blockers?
- not degraded or metabolized by acetylcholinesterase
- keeps gate open, cell cannot repolarize, cannot generate another action potential
- sodium cannot came in
Order of muscle paralysis?
- small muscles of face, eyes, head, neck
- muscles of limbs, then trunk
- respiratory muscles (intercostals), diaphragm is last
-recovery in reverse order
What can reverse the effects of non depolarizing blockers?
- reversed by acetylcholinesterase inhibitors
- Neostigmine, Pyridostigmine
- acetylcholine is longer being broken down, can compete for spots
Atracurium?
- acetylcholine is hidden in structure
- side chains make it an antagonist
- nondepolarizing blocker
- inactivated in plasma and undergoes spontaneous decomposition (degradation)
- it breaks down to Laudanosine (causes seizures in high blood concentrations), does not exert muscle paralysis
Cisatracurium?
- stereoisomer of Atracurium
- less side effects
- used more clinically
Tubocurarine?
- nondepolarizing blocker
- quaternary, charged
- requires IV
Effects:
- binds to ganglionic receptors, blocks them, causes hypotension
- causes histamine release, leads to bronchospasm
- augmented hypotension
- increased salivary/GI secretions
- skin hives
Pancuronium?
- possesses antimuscarinic (anticholinergic) effect to block receptors
- nondepolarizing blocker
- little ganglion block, less histamine release than Tubocurarine
Effects:
- causes increased HR
- increased release of NE, leads to increased HR
Vecuronium?
- intermediate acting (1 hour)
- used more than pancuronium as an adjunct to general surgery
- nondepolaring blocker
What happens in high doses of “onium” drugs?
- normally they are selective for nicotinic ACh
- in high doses they can hit muscarinic receptors and slow down HR
- causes severe bradycardia and less perfusion of oxygenated blood to tissues
Succinylcholine?
- short acting depolarizing drug (15 mins)
- induces phase 1 (depolarizing)
- effect could last for hours due to genetic variation
Effects:
- may cause malignant hypothermia
- increases K+ in blood in burn, head trauma, spinal cord injuries, and neuromuscular disease in patients
- hyperkalemia can lead to cardiac arrest
Antidote to depolarizing drugs?
- no antidote
- receptor is desensitized
- respiratory paralysis patient requires ventilation until drug wears off
Malignant hypothermia?
- ryanodine receptor defect
- causes massive release of calcium inside cell (succinylcholine makes it worse)
- causes rigor mortis rigidity, increased body temp, tachycardia, acidosis, death
Dantrolene?
- selective to ryanodine receptor, blocks it
- prevents massive release of calcium in skeletal muscle
- antidote to malignant hypothermia
- little effect on cardiac sarcoplasmic reticulum
Effects:
- most effective in spasticity of cerebral origin
- decreases muscle stiffness
ADR:
- muscle weakness
- GI disturbance
- Hepatotoxicity
What happens when Tubocurarine is administered with an “onium” drug?
- both are non depolarizing muscle blockers, so the effects are additive
- phase 1 antagonistic
- phase 2 augmented
What happens when succinylcholine is admininstered with an “onium” drug?
- will be antagonistic
- additive for phase 1
- augmented for phase 2
What happens when Neostigmine is administered with an “onium” drug?
- will be antagonistic
- phase 1 is augmented
- phae 2 is not predictable, antagonistic
What is the Train of Four?
- last muscle response divided by first response
- wont take patient off ventilation until TOF=0.7
Nondepolarizing blocker (Pancuronium) -TOF is 0.4
Depolarizing blocker (Succinylcholine)
- phase 1- constant but diminished, TOF=1.0
- phase 2- TOF=0.4
What is Fade?
- when a nerve is stimulated, ACh is released, some is eaten up by acetylcholinesterase
- Succinylcholine competes for spots on the receptor, blocks ACh
- ACh in nerve terminal won’t uptaken or be fully replenished because it is broken down
- another twitch happens, less response until no response
- fades as it becomes desensitized (phase 2)
Antispastic drugs?
- Diazepam
- Baclofen
- Dantrolene
- Tizanidine (Alpha 2 agonist)
Tizanidine?
Mechanism:
- interacts with Alpha 2 receptors, inhibits adenylate cyclase, less cAMP, less calcium coming in
- less calcium causes inhibition of excitatory neurotransmitter release (glutamate) to fuse with synaptic cleft and interact with receptor, leads to less neurotransmission
Effects:
-reduces muscle spasticity associated with cerebral and spinal disorders
ADR:
- dry mouth
- drowsiness
- asthenia (muscle weakness)
- hypotension
Baclofen?
Mechanism:
- stimulates GABAb receptors in spinal cord to open K+ channels
- increases K+ leaking out of cell, hyper polarization
Effects:
- reduces depolarization, inhibitory
- slows down CNS
- reduces spasticity
ADR:
- drowsiness
- confusion
- GI distend (nausea, diarrhea, constipation)
- allergric skin reactions
Benzodiazepine?
Mechanism:
- interacts with GABAa receptors
- increases Cl- ion influx
- hyperpolarizes cell
- increases inhibitory effect of GABA
Effects:
- Limbic- anti anxiety
- Reticular formation- sedation/hypnosis
- Cortex- anticonvulsant
- Spinal cord- skeletal muscle relaxation
- barbiturates keep channel open longer, dangerous, become physically dependent
- flumazenil, zolpidem fairly safe
Diazepam?
-drug class of Benzodiazepine that binds GABAa, causes influx of Cl-
- sedative
- anti anxiety
- anticovulsant/seizure effects
- used for muscle spasms
Mivacurium?
short acting non depolarizing agent
Cyclobenzaprine?
-acute use spasmolytic
