Nueromuscular Blockers Flashcards
T/F: Neuromuscular blockers DO provide anesthetic and analgesics.
FALSE
What receptor does acetylcholine work at?
Nicotinic Receptor
T/F: Acetylcholine activates both arms of the autonomic system. (Para-sympathetic and sympathetic)
TRUE
Choline and Acetyl CoA make what?
Acetylcholine
T/F: Acetylcholine is calcium mediated action potential.
TRUE
What deactivates Acetylcholine?
Acetylcholinesterase –> (Breaks DOWN to acetate and choline)
T/F: On the nicotinic receptor only one ACh alpha receptor has to be filled for the activation of the K+Na-ATP pump.
FALSE
Define a depolarizing neuromuscular blocker
Depolarize the muscle fiber leaving it constantly stimulated and unable to be affected by ACh.(Succinylcholine)
Define a non-depolarizing neuromuscular blocker.
Competitively block Ach from biding to receptors postsynaptically.
Define ED 95.
Dose of NMB necessary to produce 95% suppression of the single twitch response
Describes potency during nitrous oxide-barbiturate-opioid anesthesia
With volatile anesthetic: greatly reduced
2x ED95 dose = tracheal intubation
What are the first muscles to go when using a NMB?
Small rapidly moving muschels first (Eyes, fingers)
What are the last muscles to go when using a NMB?
Abd. muscle (Diaphram)
What is the structure activity relationship of NMB?
Quaternary ammonium Highly ionized, water soluble Vd similar to extracellular fluid volume No CNS effects Will no absorb orally Does not cross placenta Binds to alpha subunit post-synaptically
What structure activity relationship are NOT completely specific?
Cardiac muscarinic receptors
Autonomic ganglia nicotinic receptors
Pharmacokinetics of NMB
Not highly protein bound
Not effected by volatile anesthetics (PHARMODYNAMICS interaction)
Name one depolarizing drug.
Succinylcholine (Only One)
Name a long acting non-depolarizing NMB drug.
Pancuronium (Pavulon) (A)
Doxacurium (Nuromax) (B) Pipecuronium (Arduan) (A)
Name intermediate acting non-depolarizing NMB drug.
Atracurium (Tracrium) (B)
Vecuronium (Norcuron) (A)
Rocuronium (Zemuron) (A)
Cisatracurium (Nimbex) (B)
Name a short-acting non-depolarizing NMB drug
Mivacurium (Mivacron) (B)
What is the onset and duration of succinylcholine?
30-60 seconds (Onset)
3-5 minutes (duration)
What is the method of action for succinylcholine?
MOA: Binds one or both alpha subunits at nicotinic receptor. Mimics ACh
Minor presynaptic effects
Important postsynaptic effects
Leakage of potassium out of the cell for extended time: Increase K by ~0.5 meq/L
T/F: Succinylcholine has slower hydrolysis which equals longer duration than ACh.
True
T/F: Receptors cannot respons to subsequent ACh molecules when succinylcholine is used.
TRUE
What occurs during phase 1 blockade of succinylcholine?
-Depolarizing block- receptor stimulation
-Decreased contraction in response to single twitch stimulation
-Decreased amplitude by sustained response to continuous stimulation
-TOF ratio >0.7
-Absence of POSTTENANIC facilitation
Augmentation of neuromuscular blockade after reversal agent
Accompanied by fasiculations at onset
T/F: There is no increase in K+ in the blood serum when using succinylcholine?
FALSE
What occurs during Phase 2 of Succinylcholine?
Desensitization: Similar to non-depolarizers
May be antagonized by a reversal agent
Manifests as tachyphylaxis
What is the dose of Succinylcholine?
Tracheal Intubation 1 mg/kg IV
Minimum Does: 0.56 mg/kg
MAX Dose: 1.5 mg/kg
Plasma Cholinesterase of Succinylcholine.
Hydrolyzes SCh
Metabolite very weak NMB
Hydrolyzed again to succinic acid and choline
Must diffuse away from the NMJ to plasma to be metabolized
Severe liver disease, neostigmine, high estrogen levels reduces amount
Reglan inhibits enzyme
Increased in obese patients
Atypical cholinesterase may be present
What are the side effects of Succinylcholine?
Sinus bradycardia, junctional rhythm, sinus arrest
Cardiac muscarinic receptors- mimics ACh
Increased risk: 2nd dose within 5 minutes
Atropine will not help
May increase heart rate and BP due to ANS ganglia stimulation
What can you do to reduce side effects?
Pretreatment with a non-depolarizer may reduce side effects
All except hyperkalemia
Consideration of hyperkalemia with Succinylcholine?
Increased risk
Muscular dystrophy
Third degree burns
Skeletal muscle atrophy or severe trauma
Upper motor neuron lesions
May develop within 96 hours, last up to 6 months or more
Very high risk: male children with undiagnosed myopathy
What myalgias of succinylcholine?
Neck, back, abdomen
High risk: young adults, minor surgical procedures, early ambulation
Unsynchronized contractions?
Pediatric patients: Myoglobinuria: possible damage
Where might increased pressure may be seen at with Succinylcholine?
Intragastric: Inconsistent, possibly related to intensity of fasiculations Increased risk of aspiration Intraocular 2-4 min post-admin Transient Intracranial Low risk, not normally observed
Generals about nondepolarizing NMB?
MOA: Compete with ACh for alpha subunits at nicotinic receptors
Mostly postjunctional
Characteristic Responses
Decreased twitch response to single stimulus
Unsustained response during continuous stimulation
TOF ratio <0.7
Posttetanic potentiation
Potentiation or other nondepolarizers
Antagonism by anticholinesterases
Cardiovascular effect of Nondepolarizing NMB?
Histamine release (Atracurium, Mivacurium)
Cardiac muscarinic receptors (Pancuronium)
Nicotinic autonomic ganglia (mostly SCh)
Rarely achieve clinical significance
Most have a wide “autonomic margin of safety”
What are some critical myopathy with nondepolarizing NMB?
Long term paralysis for mech ventilation (>6 days)
Unpredictable duration
More common with aminosteroids
Higher risk with corticosteroids given
What are the allergic responses to nondepolarizing NMB?
Possible cross-sensitivity
Single quaternary ammonium groups less risk than SCh
Females have higher incidence
Soaps and cosmetics with quat groups desensitize patient
T/F: Women are more sensitive to nondepolarizing NMB?
TRUE
What is the onset and duration of Pancuronium?
Onset; 3-5 minutes
Duration: 60-90 minutes
What is the ED95 of Pancuronium?
0.07 mg/kg
What class is Pancuronium?
Long acting
Bisquaternary aminosteroid
How is Pancuronium eliminated?
80% through the urine unchanged
What metabolite does Pancuronium produce?
3-desacetylpancuronium (half as potent)
What are the cardiovascular effects of Pancuronium?
Increase heart rate
Increased MAP
Increased cardiac output
Mechanism: vagal blockade; SNS activation; muscarinic interference
Dysrhythmias, esp. in combo with Digoxin
T/F: Pancuronium is enhanced by respiratory acidosis.
TRUE
Aging will have what effect on Pancuronium?
Reduced clearance
What is the onset and duration of Doxacurium?
Onset: 4-6 minutes
Duration: 60-90 minutes
What class is Doxacurium (Neuromedics)?
Long acting
Benzylisoquinolinium, bisquaternary
What is the ED 95 of Doxacurium?
0.03 mg/kg
T/F: Doxacurium has no cardiovascular effects.
TRUE
T/F: Doxacurium dose will INCREASE with volatile anesthetics.
FALSE
What is the onset and duration of Pepecuronium?
Onset: 3-5 minutes
Duration: 60-90 minutes
What is the ED 95 of Pipecuronium?
0.05-0.06 mg/kg
What class is Pepecuronium.
Long acting
Bisquaternary aminosteroid
T/F: There are NO cardiovascular and hepatic effects with pipecuronium.
TRUE
What about use of Pipecuronium with infants?
Increase potency and shorter duration
What is typical of intermediate NDNMB?
Better clearance
All have similar onset (except Roc)
1/3 duration of long acting
Faster recovery rate than long acting
Minimal to no cardiovascular side effects
Reliably reversal by anticholinesterase drugs
What is the priming principle with intermediate NDNMB?
Priming principle Alternative to SCh for intubation 1: Small dose binds spare receptors no clinical effect 2: 4 minutes later deliver the rest deepens the neuromuscular blockade rapidly Just give Roc x1
What is the onset and duration of Atracurium?
Onset: 3-5 minutes
Duration: 20-35 minutes
What class is Atracurium?
Bisquaternary benzylisoquinolinium
(Intermediate acting)
What is the ED 95 of Atracurium?
0.2 mg/kg
How much Atracurium is protein bound?
82% (albumin)
Does Atracurium have a slow clearance effect?
NO (rapid clearance)
Describe Hoffman elimination.
Spontaneous at normal body temp and pH
Accelerated by alkalosis, slowed by acidosis
Both Atracurium and Cisatracurium
HE hydrolysis HE
Laudanosine Metabolite
Independent of renal and hepatic function
Safety net of elimination
What is laudanosine during the Hoffman elimination?
CNS stimulant
Inactive at NMJ
Peripheral vasodilation
Increase MAC of volatile anesthetics
What is the electrophillic acrylates in the hoffman effect?
Capable of damaging cell membranes
Clinical significance unknown
T/F; Infants that receive atracurium get half a dose of older children.
True (more sensitive and faster clearance)
What cardiovascular effect does atracurium have?
At x3 ED 95
increase HR
Decrease MAP
T/F: Histamine release occurs with Atracurium?
True
What is the onset and duration of Cisatracurium?
Onset: 3-5 minutes
Duration: 20-35 minutes
What is the ED 95 of Cisatracurium?
0.05 mg/kg
What class is Cisatacurium?
Bisquaternary Benzylisoquinolinium
Intermediate
T/F; Cisatracuium will have a prolong effect in the obese patient.
True
T/F: There is no cardiovascular effect with Cisatracurium.
TRUE
T/f: Hoffman elimination occurs with Cisatracurium and Atracuium.
TRUE
What is the onset and duration of vecuronium?
Onset: 3-5 minutes
Duration: 20-35 minutes
What is the ED 95 of Vecuronium?
0.05 mg/kg
What class is vecuronium?
Monoquaternary aminosteroid
intermediate
T/F:Vecuronium deals both with hepatic and renal clearance.
True
What is the metabolite of vecuronium?
- 3-desacetylvecuronium
- Half as potent
- converted to 3,17-desacetylvecuronium
Vecuronium is ___% unchanged in the bile.
40
Vecuronium is __% unchanged in the urine.
30
T/F: Vecuronium does not have any cardiovascular changes.
TRUE
Hypercarbia post injection enhances effect of _________.
Vecuronium
Vecuronium has less Vd than ________, but more than _________.
pancuronium, atracurium
Vecuronium duration is _______ in infants and _______ in children.
longest, shortest
What is the onset and duration of Rocuronium?
Onset: 1-2 minutes
Duration: 20 -35 minutes
What class is Rocuronium?
Monoquaternary aminosteroid
intermediate
What is the dose of rocuronium ED 95.
0.3 mg/kg
Rocuronium x3-x4 ED95 mimics ________.
PANCURONIUM
Rocuronium is excreted unchanged in the _____.
bile
Rocuronium is prolonged in _______ dysfunction.
renal
Cardiovascular effect of rocuronium.
Slight vagolytic effect—>no CV effect with rapid infusion.
No histamine effect.
What is the onset and duration of Mivacurium?
Onset: 2-3 minutes
Duration: 12-20 minutes
What is the ED 95 dose of Mivacurium
.08 mg/kg
What class is mivacurium?
Bisquaternary benzylisoquinolinium
Fast acting
T/F: Mivacurium has inactive metabolites.
True
Mivacurium is hydrolyzed by ________ _______.
Pasma cholinesterase
T/F: Neostigmine reduces plasma cholinesterase?
True
T/F; Burn injury has less cholinesterase activity.
True
Cardiovascular effect of mivacurium.
- Decrease MAP
- Hypotension prominent in hypertensive patients
- Possibly risk of bonchospasm.
