NMJ Blocking Drugs Flashcards
Atracurium
- 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
Cisatracurium
- Non-depolarizing
- Less is altered by Hoffman reaction, so less worry of side effects
- Average potency (1.5) with average duration (20-35 min)
D-Tubocurarine
- Non-depolarizing
- A standard that isn’t used therapeutically
- Standard potentcy (1)
- Can result in dysregulation of autonomic ganglia from interactions on spinal cord
Pancuronium
• 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
Rocuronium
• 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
Vecuronium
• 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
Succinylcholine
• 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
Succinylcholine Side Effects
- 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)
Malignant Hyperthermia
• 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
Neostigmine + Glycopyrrolate
• 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
Pyridostigmine + Glycopyrrolate
• 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
Edrophonium + Atropine
• 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
Scopolamine
another muscarinic Ach blocker but isn’t used because it crosses the BBB
Sugammadex
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
Carisoprodol
• 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
Cyclobenzaprine (important)
• 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
Methocarbamol
• 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
Tizanidine
- Skeletal muscle relaxant
* Pre-synaptic a2-receptor agonist resulting in reduced muscle tone but not muscle strength
Baclofen (important)
• 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
Dantrolene
• 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
Botulinum toxin
• 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
Duloxetine
• Fibromyalgia Drug • Serotonin-Norepinephrine Reuptake inhibitor (antidepressant) o Serotonin > norepinephrine o No effect on dopamine reuptake o BBW: Suicidal ideation
Milnaciptral
• Fibromyalgia Drug • Serotonin-Norepinephrine Reuptake inhibitor (antidepressant) o Norepinephrine > serotonin o No effect on dopamine reuptake o BBW: Suicidal ideation
Pregabalin
• 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
