Neuromuscular Blocking Agents Flashcards
Structure of NMB
Quaternary Ammoniums
Structurally related to Ach
Synthetic Alkaloids
except Tubocuraine
Structure of Succinylcholine
Two ACh molecules linked by acetate methyl groups
Dose of Succinylcholine
1.0mg/kg
How long does Succinylcholine take to work?
60 seconds
How long does it take to recover 90% muscle strength?
9-13 minutes
Metabolism of Succinylcholine
short action due to rapid hydrolysis
Enzyme that breaks down Succinylcholine
butrylcholinesterase
Metabolites of Succinylcholine
Succinylmonocholine and choline
Succinylmonocholine is a
weak NMB; succinic acid and choline
Where does recovery from succinylcholine motor blockade occur?
as it drifts away from NMJ down a concentration gradient
Where is butyrylcholinesterase metabolized?
liver and found in plasma
What is butyrylcholinesterase responsible for the metabolism of?
succinylcholine, mivacurium, procaine, chloroprocaine, tetracaine, cocaine and heroin
Factors that decrease butyrylcholinesterase activity?
advance liver disease age malnutrition pregnancy burns oral contraceptives MAO inhibitors echothiophate cytotoxic drugs neoplastic disease anticholinersterase drugs
Beta Blockers will
cause a mild prolongation of Succinylcholine
Genetic variations with the administration of succinylcholine
will significantly prolongation
Dibucaine
local anesthetic that inhibts typical PchE
Reflects the typical PChE not quantity
dibucaine number
Heterogenous for atypical gene
dibucaine number 40-60
Prolongs block 1.5-2times longer
Homogenous for atypical gene
dibucaine number less then 30
prolonged for 4-8 hours
Cardiac Side Effects of Succinylcholine
bradycardia, tachycardia junctional rhythm sinus arrest due to muscarinic receptors on cardiac cells
Cardiac effects due to succinylochine are more likely to occur
second dose within 5 minutes of first dose
pediatric patients
Stimulation of autonomic ganglia may cause
ventricular dysrhythmias
tachycardia
increased BP
Hyperkalemia
0.5-1mEq/L increase in plasma concentration
More severe in: burns, abdominal infectinos, metabolic acidosis, closed head injury and conditions with upregulation of nAChR (paraplegia, muscular dystrophy, Gullian-Barre)
Myoglobinuria
damage to skeletal muscle especially pediatric patients
Most found to have muscular dystrophy or by malignant hyperthermia susceptible
Increased intraocular pressure
peaks 2-4 minutes; pressure returns to normal by 6 minutes
not widely accepted in open eye injury
Increased intragastric and lower esophageal pressures
related to intensity of fasciculations of abdominal muscles
Prevented by prior administration of ND-NMB
does not increase risk of regulation
Increased intracranial pressure
can be attenuated with pre-treatment of ND-NMB
Masseter Spasm
trigger for MH
Myalgias
prominent in skeletal muscle of the neck, back and abdomen
greater in young adults females and ambulatory surgery patients
not well understood possible muscle injury to fasciculations
pretreatment with ND-NMV lidocaine or NSAIDs
myalgias occur even in absence of succinylcholine
Elderlys (sux)
onset slower due to decreased circulation
reduced levels of PChE
certain alzheimer medications may prolong actions
Pediatrics (suc)
avoided in pediatric patients (<5 yrs)
Duchenne muscular dystrophy
Cardiac arrest him from hyperkalemic rhabdomyolysis
Atricurium
Histamine Release
Structure of Cis
cis isomer of atracuurium
Onset of action of Cis
intermediate
Intubation Dose of Cis
0.1mg/kg
Cis is metabolized
by Hoffman elimination
No ester hydrolysis
Does cis cause histamine release?
no
DOA of Mivacurium
short acting non-deplorizing available
Intubating dose of mivacurium
0.15mg/kg
Mivacurium is metabolize by
butyrylcholinesterase
70-88% rate of succinylcholine
monoester, dicarboxylic acid
Mivacurium produces
histamine release
Steriodal compounds include
pancuronium
vecuronium
rocuronium
Steriodal compounds structure
acetyl ester thought to facilitate interaction with NaChR
essential that one of two nitrogen atoms are quarternized
DOA of Pancuronium
Potent long acting neuromuscular blocking drug
Intubation dose of Pancuronium
0.08mg/kg
Onset time to max block of pancuronium
2.9 minutes
Majority of Pancuronium is cleared
by the kidney
Other small amount of Pan is
deacteylated by the liver
3-OH metabolite
Pancuronium
accumulation is responislbe for block prolongation
DOA of Vec
intermediate Acting
Intubating dose of VEc
0.1mg/kg
Onset time to max block of Vec
2.4 minutes
What drug is Vec similar
pancuronium without quaternized methyl group
What are the differences in properties between vec and pan?
slight decrease in potency
loss of vagolytic properties
Molecular instability (shorter DOA)
increase lipid solubility
Where is Vec metabolized
principally by the liver
3-OH metabolites has 80% of neuromuscular potency
DOA of Roc
Intermediate
Intubation dose of Roc
0.6mg/kg
Time to Max block in roc
1.7 minutes
Roc has a faster onset than
pan or vec
Roc potency is x times less potent then
pan or vec
Roc is primarily metabolized
in the liver
approximately 30% executed in the urine
NMB Potency increased
inhalational agents antibiotics hypothermia magnesium sulfate local anesthetic quinidine
Factors that decrease NMB potency
chronic anticonvulsant administration
hyperparathyroidism and hypercalcemia
(decreased atracurium sensitivity)
With NMB potency and onset
have an inverse relationship
Buffered Diffusion seen with
high density drugs
drug diffusion is impeded because it binds to high density receptors in a confined space
Autonomic Effects of NMB
block nicotinic receptors within sympathetic and parasympathetic nervous system
bradycardia and hypotension
histamine release (flushing, hypotension, reflex tachycardia and bronchospasm)
Vagolytic effects occur
pancurium
block muscarinic receptors
inhibition of negative feedback system where catecholamine release is modulated or prevented
Histamine Release
seen in benzylisoquinolinium (miv, atra, tubo)
short duration
slow administration or pretreatment with H1 and H2 blockers to reduce cardiovascular effects
Respiratory effects of NMB
related to histamine release in patients with reactive airways disease
increasd airway resistance and bronchospasm
Allergic Reactions
cross reactivity =- food, cosmetics, disinfections, and industrial materials
treatment of allergic reaction
o2 IV epi intubation fluids sympathomimetic drug
