NMJ Blocking Drugs

Question 1

Atracurium

Answer 1

• Non-depolarizing
• Eliminated via non-enzymatic Hoffman reaction
• Results in laudanosine toxic metabolite production that can induce seizure
• Average potency (1.5) with average duration (20-35 min)
• Mast cell histamine release may result in hypotension from increased vascular

Question 2

Cisatracurium

Answer 2

• Non-depolarizing
• Less is altered by Hoffman reaction, so less worry of side effects
• Average potency (1.5) with average duration (20-35 min)

Question 3

D-Tubocurarine

Answer 3

• Non-depolarizing
• A standard that isn’t used therapeutically
• Standard potentcy (1)
• Can result in dysregulation of autonomic ganglia from interactions on spinal cord

Question 4

Pancuronium

Answer 4

• Non-depolarizing
• High potency (6) with average duration
• Tachycardia from blocking M2/M3 receptor action on heart may occur
o All are metabolized by the liver to 3-OH metabolites then renally eliminated
o Best used in long duration procedures

Question 5

Rocuronium

Answer 5

• Non-depolarizing
• Standard potency (0.8) with average duration
o All are metabolized by the liver to 3-OH metabolites then renally eliminated
o Best used in long duration procedures

Question 6

Vecuronium

Answer 6

• Non-depolarizing
• High potency (6) with average duration
o All are metabolized by the liver to 3-OH metabolites then renally eliminated
o Best used in long duration procedures

Question 7

Succinylcholine

Answer 7

• Depolarizing
o Extremely short half-life (5-10 minutes); good for quick/emergent paralysis induction
o Weak potency (0.4)
o Worry of variant pseudocholinesterase that can result in increased duration of action

Question 8

Succinylcholine Side Effects

Answer 8

• Mast cell histamine release may result in hypotension from increased vascular permeability
• Hyperkalemia occurs with Ach receptor upregulation in a pathologic process
• Muscle stimulation causes mass Na+ influx and K+ efflux from the muscle tissue, resulting in hyperK
• Muscle pain can result from intense fasciculation in phase I
• Malignant Hyperthermia (on another card)

Question 9

Malignant Hyperthermia

Answer 9

• genetically driven hypermetabolic response
• Autosomal dominant mutation in ryanodine receptor 1 (RyR1), which is the mediator of calcium release from the sarcoplasmic reticulum to initiate muscle contraction
• RyR1 uncontrollably releases Ca2+ resulting in:
o Contraction (rigor)
o Increased skeletal muscle metabolism (CO2 and heat)
o ATP depletion (lactic acidosis)
• Treatment seeks to reverse the symptoms
o Remove succinylcholine application
o Dantrolene uncouples RyR1 from stimulation, thus stops Ca2+
o Physical cooling/O2 hyperventilation
o Correction of acidosis

Question 10

Neostigmine + Glycopyrrolate

Answer 10

• AchE inhibitor with it’s muscarinic Ach Blocker
o These CANNOT displace the NMJ blocker, but can speed recovery rate once it’s started
o When we see some twitch coming back, that’s when we dump the AchE inhibitors on them

Question 11

Pyridostigmine + Glycopyrrolate

Answer 11

• AchE inhibitor with it’s muscarinic Ach Blocker
o These CANNOT displace the NMJ blocker, but can speed recovery rate once it’s started
o When we see some twitch coming back, that’s when we dump the AchE inhibitors on them

Question 12

Edrophonium + Atropine

Answer 12

• AchE inhibitor with it’s muscarinic Ach Blocker
o These CANNOT displace the NMJ blocker, but can speed recovery rate once it’s started
o When we see some twitch coming back, that’s when we dump the AchE inhibitors on them

Question 13

Scopolamine

Answer 13

another muscarinic Ach blocker but isn’t used because it crosses the BBB

Question 14

Sugammadex

Answer 14

o Stops action of steroidal paralytics
o Current method is to simply stop the drug (slow!)
o Acts as a little net to trap the steroidal paralytic so it cannot bind to the Ach receptor

Question 15

Carisoprodol

Answer 15

• Skeletal muscle relaxant
• Works on central CNS (reticular activating system) and spinal cord
o Results in sedation/altered response to pain
o No direct effect on neuronal conduction/NMJ transmission

Question 16

Cyclobenzaprine (important)

Answer 16

• Skeletal muscle relaxant
• Works centrally to relieve muscle spasm/pain; not well characterized
• Extensive hepatic metabolism with enterohepatic circulation
o Reduced clearance in elderly and liver dysfunction
• Anti-cholinergic activity = major side effect; contraindicated with
o Sedative drugs and alcohol
o 1st generation antihistamines
• Also can cause GI problems like paralytic ileus

Question 17

Methocarbamol

Answer 17

• Skeletal muscle relaxant
• Works on central CNS (reticular activating system) and spinal cord
o Results in sedation/altered response to pain
o No direct effect on neuronal conduction/NMJ transmission

Question 18

Tizanidine

Answer 18

• Skeletal muscle relaxant

* Pre-synaptic a2-receptor agonist resulting in reduced muscle tone but not muscle strength

Question 19

Baclofen (important)

Answer 19

• Spasticity Drug
• GABAb agonist that works at multiple levels of the spinal cord either as an inhibitor or exciter of neural transmission
o Therapeutic effect is due to inhibition of Substance P
• Extensive liver metabolism
• Contraindications/side effects
o Renal failure → drug accumulation → encephalopathy/seizure/respiratory depression
o BBW of ‘rebound’ neural activity (seizure/increased spasticity/hallucinations)
• Works the same way as diazepams (these work on GABAA)
• Must be tapered off because it produces dependence

Question 20

Dantrolene

Answer 20

• Spasticity Drug
• Decreases muscular contraction by directly interfering with calcium ion release from the sarcoplasmic reticulum via ryanodine receptors (excitation no longer causes Ca2+ release)
• Useful for treatment of malignant hyperthermia
• Only affects skeletal muscle at proper doses
• Contraindications/toxicities
o Crosses the placenta, may result in floppy baby syndrome if used in C-section
o Don’t use with calcium channel blockers, can cause Ventricular fibrillation/CV collapse

Question 21

Botulinum toxin

Answer 21

• Spasticity Drug
• Inhibits release of Acetylcholine through inhibition of intra-neuronal vesicle fusion
o Toxin is endocytosed by the neuron
o After entering the neuron cytoplasm, the toxin cleaves SNAP-25 and SNARE proteins needed for vesicle fusion to allow for neurotransmitter release
o Halts the release of neurotransmitter, resulting in muscle paralysis

Question 22

Duloxetine

Answer 22

•	Fibromyalgia Drug
•	Serotonin-Norepinephrine Reuptake inhibitor (antidepressant)
o	Serotonin > norepinephrine
o	No effect on dopamine reuptake
o	BBW: Suicidal ideation

Question 23

Milnaciptral

Answer 23

•	Fibromyalgia Drug
•	Serotonin-Norepinephrine Reuptake inhibitor (antidepressant)
o	Norepinephrine > serotonin
o	No effect on dopamine reuptake
o	BBW: Suicidal ideation

Question 24

Pregabalin

Answer 24

• Fibromyalgia Drug
• Inhibits presynaptic a2∆ subunits of L-type calcium channels
o Stops excitatory transmission of glutamate presynaptically, which alleviates symptoms
• Rapid absorption with little metabolism and renal excretion
o Serum creatinine should be monitored (kidney function determines amount in body)
• Rebound worsening of symptoms may occur upon withdrawal of drug