Neuromuscular Blockers

Question 1

Use of the “oniums?”

Answer 1

• adjunct for general surgery

- helps manage diaphragm, so don’t have to use as much anesthetic

Question 2

Difference between nicotinic and muscarinic acetylcholine receptors?

Answer 2

• nicotinic is comprised of multiple subunits
• ligand gated ion channel
• two alpha subunits need to be bound by acetylcholine to activate it

Question 3

Role of skeletal muscle blocking drugs?

Answer 3

• block effects of ACh at nicotinic muscle receptors (Nm)

- used during surgery for paralysis of muscles (diaphragm)

Question 4

Nondepolarizing blockers?

Answer 4

• antagonist
• competitive inhibitor of ACh
• prevents ACh from interacting and keeps gate closed

Question 5

Depolarizing blockers?

Answer 5

• not degraded or metabolized by acetylcholinesterase
• keeps gate open, cell cannot repolarize, cannot generate another action potential
• sodium cannot came in

Question 6

Order of muscle paralysis?

Answer 6

1. small muscles of face, eyes, head, neck
2. muscles of limbs, then trunk
3. respiratory muscles (intercostals), diaphragm is last

-recovery in reverse order

Question 7

What can reverse the effects of non depolarizing blockers?

Answer 7

• reversed by acetylcholinesterase inhibitors
• Neostigmine, Pyridostigmine
• acetylcholine is longer being broken down, can compete for spots

Question 8

Atracurium?

Answer 8

• 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

Question 9

Cisatracurium?

Answer 9

• stereoisomer of Atracurium
• less side effects
• used more clinically

Question 10

Tubocurarine?

Answer 10

• 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

Question 11

Pancuronium?

Answer 11

• 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

Question 12

Vecuronium?

Answer 12

• intermediate acting (1 hour)
• used more than pancuronium as an adjunct to general surgery
• nondepolaring blocker

Question 13

What happens in high doses of “onium” drugs?

Answer 13

• 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

Question 14

Succinylcholine?

Answer 14

• 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

Question 15

Antidote to depolarizing drugs?

Answer 15

• no antidote
• receptor is desensitized
• respiratory paralysis patient requires ventilation until drug wears off

Question 16

Malignant hypothermia?

Answer 16

• ryanodine receptor defect
• causes massive release of calcium inside cell (succinylcholine makes it worse)
• causes rigor mortis rigidity, increased body temp, tachycardia, acidosis, death

Question 17

Dantrolene?

Answer 17

• 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

Question 18

What happens when Tubocurarine is administered with an “onium” drug?

Answer 18

• both are non depolarizing muscle blockers, so the effects are additive
• phase 1 antagonistic
• phase 2 augmented

Question 19

What happens when succinylcholine is admininstered with an “onium” drug?

Answer 19

• will be antagonistic
• additive for phase 1
• augmented for phase 2

Question 20

What happens when Neostigmine is administered with an “onium” drug?

Answer 20

• will be antagonistic
• phase 1 is augmented
• phae 2 is not predictable, antagonistic

Question 21

What is the Train of Four?

Answer 21

• 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

Question 22

What is Fade?

Answer 22

• 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)

Question 23

Antispastic drugs?

Answer 23

• Diazepam
• Baclofen
• Dantrolene
• Tizanidine (Alpha 2 agonist)

Question 24

Tizanidine?

Answer 24

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

Question 25

Baclofen?

Answer 25

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

Question 26

Benzodiazepine?

Answer 26

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

Question 27

Diazepam?

Answer 27

-drug class of Benzodiazepine that binds GABAa, causes influx of Cl-

• sedative
• anti anxiety
• anticovulsant/seizure effects
• used for muscle spasms

Question 28

Mivacurium?

Answer 28

short acting non depolarizing agent

Question 29

Cyclobenzaprine?

Answer 29

-acute use spasmolytic