NMBs Flashcards
1
Q
Succ: class
A
ONLY depolarizing neuromuscular blocking agent
2
Q
succ: MOA
A
- binds to one or both of the alpha subunits of nicotinic Ach receptors & mimics the action of Ach (partial agonist)
- → depolarizes the post-junctional membrane
- → brief period of excitation (fasciculations in muscle cells), followed by flaccid paralysis from open cholinergic channels maintaining the cell membrane in a depolarized condition
- (inactivated voltage-gated Na+ channels = no action potentials)
3
Q
Succ: PK
A
- Onset (average time to intubating conditions): 30-90 sec
- DOA: 5-10 min
- E ½ life: 47 seconds
- Water soluble
- Vd: small (0.2 L/kg) similar to ECF; Plasma cholinesterase has an enormous capacity to hydrolyze Sch at a rapid rate, so that only a small fraction of the original IV dose of the drug actually reaches the NMJ
- PB: not clinically insignificant
- Metabolism: Termination of effect due to diffusion away from the NMJ down concentration gradient and then rapidly hydrolyzed by pseudocholinesterase (not acetylcholinesterase) to succinylmonocholine and choline
4
Q
succ: SE
A
- CNS:
- ↑ ICP*, IOP
- CV:
- ANS ganglionic stimulation: ↑ HR/BP; autonomic stimuli can also cause ventricular dysrhythmias during laryngoscopy
- Significant bradycardia (d/t actions at cardiac muscarinic cholinergic receptors): most likely with children and/or when 2nd dose is given within ~5 minutes of first dose
- MUSCULOSKELETAL:
- masseter spasms (can be heralding sign of MH)
- myalgia*
- GI/GU:
- ↑ IGP*
- myoglobinuria
- OTHER:
- MALIGNANT HYPERTHERMIA TRIGGER
- HISTAMINE RELEASE
- Hyperkalemia – (0.5 mEq/dL ↑ in healthy patient)
- (* = may be attenuated with defasciculating dose of NDNMB)
5
Q
succ: cautions/contraindications
A
-
CAUTIONS
- Severe life-threatening hyperkalemia in patients w/
- Burns
- Severe abdominal infections
- Severe metabolic acidosis
- Closed head inury
- Conditions leading to upregulation of extrajunctional receptors
- Renal disease (increase in K) - ok to give if K < 5.5
- Asthma/COPD (histamine releaser)
- Hypersensitivity (trigger of allergic reactions more than any other drug in anesthesia)
- Genetic variation in plasma cholinesterase → Dibucaine number 20-30 → homozygous atypical → prolonged DOA 4-8 hours
- nAChR up-regulation: (*sensitivity to succ*): SCI, stroke, burns, prolonged immobility, prolonged exposure to NMBs, MS, GBS
- nAChR down – regulation (*resistance to succ*): MG, anticholinesterase poisoning, organophosphate poisoning)
- Severe life-threatening hyperkalemia in patients w/
-
CONTRAINDICATIONS
- MH
- Hyperkalemia
-
Sch Black Box: admin in children carries risk of cardiac arrest and sudden death → due to undiagnosed skeletal muscle myopathy (most commonly DMD)
- avoid in peds unless emergency!!
6
Q
succ: dose
A
- Dose off of TBW
- Laryngospasm: 20-40 mg IV or 0.3 mg/kg
- RSI/intubation: 1 - 1.5 mg/kg (1.5 mg/kg with NDNMB for defasciculating dose) No reversal agent available
- Peds RSI: 2 mg/kg IV and ALWAYS administer with .02 mg/kg atropine
7
Q
Mivacurium: class + structure
A
- class
- Benzylisoquinolone
- ONLY short acting nondepolarizing NMB
- structure
- Quaternary structure
8
Q
mivacurium: MOA
A
competitively binds to 1 or both alpha subunits of post-synaptic nicotinic AchR → prevents Ach from binding, preventing depolarization → **competitive antagonist**
9
Q
mivacurium: PK
A
- Onset (time to max block): 3.3 min
- DOA: 15-20 min
- E ½ life: 1 hr
- Vd: 0.2 L/kg; poorly lipid soluble
- Metabolism: plasma cholinesterase (butyrylcholinesterases) to monoester & quaternary alcohol → good for liver or renal failure
- Elimination: <5% excreted unchanged in urine
10
Q
mivacurium: SE
A
-
HISTAMINE RELEASE – Erythema, flushing, hypotension, bronchospasm, & tachycardia
- Hypotension caused by histamine release can be reduced or prevented if the drug is administered over 30 seconds
- dose < .15 mg/kg - little to no CV effects
11
Q
mivacurium: cautions/contraindications
A
- CAUTIONS
- Reactive airway disease → histamine
- Pts where tachycardia would be harmful → histamine: thyrotoxicosis, pheo, CAD
- Genetic variation in plasma cholinesterase → Dibucaine number 20-30 → homozygous atypical → prolonged DOA 4-8 hours
12
Q
mivacurium: dose
A
- OFF IBW
- Intubation: 0.15 – 0.25 mg/kg
13
Q
Mivacurium: misc notes
A
- good for peds (faster onset + recovery), Renal/hepatic failure, can reverse with edrophonium
- In children, mivacurium has a faster onset and more rapid recovery than in adults, so the drug can be used for intubation and maintenance of relaxation for short procedures (Barash, 435).
- In the event that mivacurium must be antagonized with an anticholinesterase, edrophonium may be preferred (Dunn, 198).
14
Q
Atracurium: class + structure
A
- class
- Benzylisoquinolone
- Intermediate Acting, non-depolarizing NMB
- structure
- Racemic mixture of 10 stereoisomers
15
Q
atracurium: MOA
A
competitively binds to 1 or both alpha subunits of post-synaptic nicotinic AchR → prevents Ach from binding, preventing depolarization → **competitive antagonist**
16
Q
atracurium: PK
A
- Onset (time to max block): 3 min
- DOA: 20-50 min
- E ½ life: 20 min
- water soluble
- PB: 82%
- Vd: .2 L/kg
- Metabolism:
-
Hofman elimination: spontaneous degradation → temp and pH dependent
- Alkalosis and hot → “burn through dose”
- Acidotic and cold → prolonged DOA
- **ACTIVE METABOLITE** (of hofman elimination) - LAUDANOSINE
- Ester hydrolysis
- Elimination: 70% excretion in bile; remainder in urine
17
Q
atracurium: SE
A
HISTAMINE RELEASE – Erythema, flushing, hypotension, bronchospasm, & tachycardia
18
Q
atracurium: cautions/contraindications
A
- CAUTIONS
- Reactive airway disease (Asthma, COPD) → histamine
- Pts where tachycardia would be harmful → histamine: thyrotoxicosis, pheo, CAD
- Seizure history → laudanosine can cross BBB, CNS stimulant
- renal dysfunction → laudanosine accumulation → seizure (unlikely occurrence)
- Hepatic cirrhosis does not alter clearance of laudanosine, but excretion impaired w/ biliary obstruction (Miller)
- Prolonged action in acidosis & hypothermia (Hoffman elimination)
