NMB Flashcards
Steps in nerve transmission and depolarization
1) AP depolarizes terminal
2) Influx of calcium –> storage vesicles fuse with membrane
3) Release ACh into synaptic cleft to bind nicotinic receptor
4) ACh receptor undergoes conformational change
5) Cations flow through open receptor -> generates end plate potential
6) End plate potential generates depolarization (VG Na channels)
7) AP propogates along muscle and T-tubules
8) Release Ca into SR –> contraction
9) ACh rapidly hydrolyzed by AChE
ACh Nicotinic Receptor
5 subunits - 2 alpha, 1 beta, 1 episilom, 1 gamma
2 alpha subunits bind to ACh and cause change
Depolarizing blocker
closely resembles ACh, is able to bind and contract
- not metabolized by AChE, so it lasts longer
- This prolonged depolarization = relaxation
Phase I Block
channels cannot re-open until the end-plate repolarizes
-> end plate cannot repolarize as long as receptor is bound
Phase II Block
After prolonged period of time, receptor changes to resemble a non-depolarizing block (unresponsive channel)
Non-depolarizing blocker
binds ACh recept at different site, doesn’t not cause the conformational change to open the ion channels, but does not allow true ACh to bind
Extrajunctional receptors
new, naïve receptors that show an exaggerated response to depolarizing blockers and resistant to non-depolarizing blockers
Succinylcholine
depolarizer
It is 2 ACh molecules linked by covalent bond
- low Vd and poor lipid solubility
FAST onset most likely from overdosing
Sux metabolism
rapidly metabolized to succinylmonocholine by pseudocholinesterase
Hypothermia = decreases rate of hydrolysis -> prolongs block
- Low pseudoChE = prolong block
Dibucaine number
measures amount of pseudocholinesterase function
~normal is 80
Sux drug interactions
Cholinesterase inhibitors = significantly prolongs sux blockade -> leads to increase [ACh]
Non-depolarizers = antagonize phase I block -> defasciculating dose
Contraindications to Sux
1) Major burn
2) Prior stroke with residual deficits
3) Malignant Hyperthermia
4) Massive trauma
5) Prolonged immobilization
6) Hyperkalemia
7) Closed head injury (?)
8) Myopathies
Sux on organ systems
CV: can stimulate all ACh receptors - the effect depends on the dominant system
MSK: fasciculations/myalgias from unsynchronized contraction - can see myoglobin in urine
Hyperkalemia: 0.5 mEq per dose, from the discharge of the nerve terminals and muscle fibers
GI: increased gastric pressure from ab wall fasciculations but also increase LES tone
CNS: increased ICP (theoretical)
Eye: increased intraocular pressure due to different receptors
Nondepolarizers
steroidals vs benzylisoquinolones
- use 2x ED95 dose for intubation
- in general the more potent, the slower speed of onset
Maintenance of Relaxation
helpful for surgical conditions, controlling ventilation and reducing the depth of anesthetic
- lots of variability between patients
- adding multiple relaxants is synergistic
Hepatic Clearance
Pancuronium and Vecuronium
Biliary Clearance
Vecuronium and Rocuronium
Renal Clearance
Vecuronium
General Pharm Characteristics
Hypothermia - prolongs blockade
Acidosis - prolongs blockade
Hypokalemia and Hypocalcemia - augments blockade
Neonates - more sensitive
Atracurium
benzylisoquinolone
EXTENSIVELY metabolized that the pharmacokinetics are independent of renal/hepatic function
Ester hydrolysis - nonspecific esterases
Hoffman Elimination - non-enzymatic breakdown
DOSE: 0.5 mg/kg
S.E. of Atracurium
Dose-dependent histamine release
Hypotension and tachycardia
Bronchospasm
Laudanosine toxicity - from Hoffman elimination = causes seizures
Free acid precipitate if given with alkaline drugs
Cisatracurium
stereoisomer of atracurium (4x as potent)
- Hoffmann Elimination (due to potency, less Laudanosine toxicity)
DOSE: 0.1-0.15 mg/kg
NO HISTAMINE RELEASE
Pancuronium
steroid ring
deacetylated in liver and excreted in urine, cirrhosis patients have longer actions
DOSE: 0.08-0.12 mg/kg
S.E. of Pancuronium
Hypertension and tachycardia from vagal blockade
Arrhythmias
Allergies
Vecuronium
steroidal with 1 less quaternary methyl group
Depends on biliary, hepatic and renal clearance
SHORT duration of action with rapid clearance
- Infusion = build up of 3-hydroxy metabolite and prolonged blockade
DOSE: 0.08-0.12 mg/kg
AVOID in renal failure
Rocuronium
monoquaternary steroidal analog
NO Metabolism: biliary elimination
Duration of action not effected by renal clearance
NO active metabolite
DOSE: 0.45-0.9 mg/kg or 1.2 mg/kg for RSI given its rapid acting nature
