Flashcards in Depolarizng NMB Deck (34)
what is the mechanism of action of depolarizing NMB?
binds to the alpha subunits of the postsynaptic nicotinic receptor and mimics ACh, causing the muscle cell membrane to depolarize.
-AChE usually hydrolyzes ACh rapidly but SCh is hydrolyzed by plasma cholinesterase
-plasma cholinesterase affects more upon initial absorption since in the plasma so controls the amount of SCh that makes it to the receptors
*once SCh binds with receptors, nothing there to hydrolyze so stays on receptor so it can't depolarize again, then acting as a blocker
*must diffuse back into plasma for termination
what is the chemical structure of SCh?
-two ACh molecules linked by acetate methyl groups
*structure makes SCh very water soluble, so it does not cross the BBB to affect the CNS
what receptors do SCh affect?
structure is similar to ACh so ACh receptors are affected:
-nicotinic cholinergic receptors at NMJ
-muscarinic receptors in the SA node
-parasympathetic nervous system
*may cause bradycardia or tachycardia
*metabolite may affect the SA node
*almost always have bradycardia with a 2nd dose
what are some indications for use of SCh?
*fast onset (45-90 seconds) and short duration (5-10 min)
-rapid intubation needed
patient has a full stomach
diabetes, hiatal hernia, obesity, pregnancy, severe
-desire short duration of action
unsure if you will be able to ventilate
*if you preoxygenate, pt can be apneic for 8 minutes
Describe phase I block of SCh.
-SCh causes depolarization and initial contractions, then paralysis
-SCh diffuses away from the NMJ and the muscle cell membrane repolarizes and can respond to future stimuli
what are the characteristics of a phase I block?
-fasciculations: initial contractions seen more with smaller muscles of the face; thought to be the cause of myalgia r/t SCh
-decreased single twitch
-lack of fade of tetanus
-minimal fade of TOF
-no posttetanic twitch
*blockade is enhanced by anticholinesterases
(Neostigmine also affects plasma cholinesterases,
the block longer
*rapid recovery, short duration of action
describe phase II blockage of SCh.
-if NMJ is repeatedly exposed (redosing or large dose) or continually exposed (drip) to SCh
-tachyphylaxis occurs and blockade changes into one much like nondepolarizing NMB
what are the characteristics of a phase II block?
-fade of tetanus and TOF in over 50%
-prolonged duration in 50% (if you realize a phase II block, stop SCh and monitor level of relaxation)
-reversible with anticholinesterases
how do you determine whether to use reversal or not if unsure of what phase is occurring?
-while monitoring the response with a peripheral nerve stimulator, give a small dose of anticholinesterase (use edrophonium since it does not affect plasma cholinesterases) 0.1-0.2 mg/kg IV
-if the block is attenuated (lessened), give remainder of dose to antagonize of the phase II block
-if the block is accentuated (enhanced), assume a phase I block and avoid additional anticholinesterase
what metabolized SCh?
Describe metabolism of SCh by plasma cholinesterase.
-rapid metabolism of SCh occurs in the plasma as soon as it is injected (80mg/min)
-Relatively little SCh reaches the NMJ, which attributes to its short duration
*once at the receptor, SCh is not metabolized by AChE, causing the depolarization and subsequent paralysis to last longer than ACh
*paralysis ends once SCh diffuses away from the muscle membrane
*ester local anesthetics and mivacurium are metabolized similar to SCh
*patients inability to metabolize SCh may be a quantity or quality issue with plasma cholinesterases
what determines the rate of diffusion of SCh from the muscle membrane?
the amount of drug that reached the junction and the concentration in the plasma
Describe plasma (pseudo) cholinesterase deficiency.
-mainly produced in the liver so a deficit may be anticipated in sever liver disease
-may also see in pregnancy (not prolonged), malignancies, malnutrition, collagen vascular disease, and hypothyroidism
*a deficit causes prolonged duration of a SCh block
describe atypical plasma cholinesterase.
-two genes dictate quality and quantity of plasma cholinesterase
*96% have both normal genes (homozygous normal) and SCh duration will be normal 5-10 min
*3.96% have one normal gene and one atypical gene (heterozygous atypical) and SCh duration is about 30min
*0.04% have both atypical genes (homozygous atypical) and SCh may last 3+ hours
how can atypical plasma cholinesterase be determined?
-if patient mention family members staying on the vent unexpectantly may test fluoride number or most commonly the dibucaine number.
what does the dibucaine number test?
-test genetic variation or the "quality" of plasma cholinesterase
-dibucaine is a local anesthetic
how are dibucaine number results interpreted?
-dibucaine normally inhibits 80% of plasma cholinesterase activity
*dibucaine # 80
*means homozygous normal
-inhibits homozygous atypical activity by 20%
-inhibits heterozygous atypical activity by 40-60%
what drugs effect plasma cholinesterases?
-neostigmine causes a decrease in plasma cholinesterase activity
-anticholinesterase drugs may cause decreased activity
*insecticides include these (be cautious of rural farmers)
*myasthenia gravis tx
-chemotherapy drugs like nitrogen mustard and cyclophosphamide may cause decreased activity
-reglan inhibits plasma cholinesterase
what other factors effect plasma cholinesterases?
-high estrogen levels during pregnancy at term reduce activity by 40% BUT usually not an issue since their increased fluid volume helps to dilute SCh and high aspiration risk due to "full stomach" outweighs so will use SCh
-other rare genes cause inability to metabolize SCh
*SCh then eliminated by the kidneys which takes longer
-obese patients may have an increased plasma cholinesterase activity, requiring an increased dose
*dose for total body weight with SCh no ideal body wt
What are some limitations or contraindications of SCh use?
-increased intraocular pressure
-increased intracranial pressure
-increased intragastric pressure
-myoglobinuria from rhabdomyolysis
-skeletal muscle contraction
-masseter muscle spasm
describe use of SCh in relation to cardiac dysrhythmias.
-may cause bradycardia due to the effect of SCh on the cardiac muscarinic cholinergic receptors; usually seen with a 2nd dose
*pretreatment with atropine does not help; have atropine ready to give if this occurs
-may cause tachycardia and HTN due to SCh stimulation effect on the sympathetic ganglion
describe contraindication of SCh with hyperkalemia.
-there is a usual increase of 0.5-1.0 meq/L
*ion channels stay open longer allowing an addition
efflux of K+
*know K+ values, especially with an ESRD pt
-an exaggerated release can lead to cardiac arrest
*proliferation of extrajunctional receptors (can start
within 5 hrs of immobilization)
*damaged muscle membranes (crush injuries)
*diseased muscle membranes (Guillain-Barre)
-burns and massive tissue trauma
*extrajunctional receptor proliferation starts within 48
hrs after burn or trauma and can last
from 6 months up to 2 years
-neurologic injuries: closed head trauma, CVA, hemiparesis, spinal cord trauma
-neuromuscular disorders: Guillain-Barre, amyotrophic lateral sclerosis, Friedreich's ataxia
describe contraindications of SCh with increased intraocular pressure.
-increase may be due to fasciculations of extraocular muscles
-max effect at 2 min with a duration of 6 min
*concern with open eye injury or patient with recent eye surgery
*pretreat with a nondepolarizing NMB may prevent the increase in pressure
describe contraindications of SCh with increased ICP.
-fasciculations cause venous compression of epidural and jugular veins
*may increase cerebral blood flow
*pretreat with nondepolarizer and lidocaine 1.5-2 mg/kg prior to intubation
*hyperventilate to drive the CO2 down and promote vasoconstriction and maintain a good airway
describe contraindications of SCh with increased intragastric pressure.
-fasciculations can increase pressure from 5-40 cmH2O
*GE sphincter can open spontaneously at >28 cmH2O
*pretreat with nondepolarizer to prevent visible fasciculations and prevent the increase of pressure
*pressure increase is related to the strength of fasciculations
describe the relationship of myalgia and SCh use.
-discomfort, painful muscle soreness r/t disorganized contraction of muscles with initial depolarization
most commonly seen in younger, muscular patients (bigger muscle mass) that are allowed to ambulate soon after surgery
-occurs in the neck, back, and abdomen
-may last up to a week
-greater incidence with propofol compared to pentothal
-decreased incidence with higher doses of SCh
what is an effective pretreatment to prevent myalgia r/t SCh?
-nondepolarizing NMB (less than 10% of ED)
*pretreatment with Vecuronium does not prevent
-Na+ channel blockers (lidocaine)
describe contraindications of SCh with myoglobinuria from rhabdomyolysis
-seen mostly with pediatric patients
-related to muscle damage from the fasciculations
-muscular dystrophy and crush injuries
*have coca cola urine, really need to hydrate to flush out kidneys
describe contraindications of SCh with malignant hyperthermia.
-at a hypermetabolic state
-muscles contract and continue to contract, using up energy and O2
*SCh is a triggering agent
*masseter muscle spasm leading to difficult airway
describe the effect of SCh on skeletal muscle contractions.
-has a prolonged effect in myotonia congenita or myotonia dystrophica
*contractures may interfere with ventilation, intubation and become life-threatening
describe the contraindication of SCh with masseter muscle spasms.
*incomplete jaw relaxation may lead to difficult airway
how does pretreatment with a nondepolarizer affect SCh dose?
increases the dose required to 1.5 mg/kg
*pretreatment does not prevent an increase in K+
what are the ED95 and intubating dose of SCh and the infusion concentration?
ED95: 0.3 mg/kg
intubating: 1-1.5 mg/kg IV
4-5 mg/kg IM
infusion: 1 gm/ 500 cc