Nagelhout Video 2- Exam 1 Flashcards
Succinylcholine structure
two ACh molecules stuck together
Succinylcholine broken down by
plasma cholinesterase
First broken down into:
succinyl-monocholine and choline
Then into
Succinic acid and choline
What is recycled to make new Ach?
Choline
What partof sux metabolism is metabolized via the kreb’s cycle?
succinic acid
Why does succinylcholine have such a brief duration?
rapid hydrolysis in plasma by cholinesterase enzyme to inactive metabolites
all the cholinesterases do the SAME thing which is-
break things down via hydrolysis - by adding water
MOST UBIQUITOUS ENZYME IN THE BODY
What are the cholinesterase family of enzymes?
hydrolytic enzymes that hydrolyze ACh and ester LAs at the synaptic cleft more quickly than others at other conditions
-allows for proper nerve signalling by preventing overstimulation
names for this family :
acetylcholinesterase (synapse of muscles)
pseudocholinesterase (plasma)
ESTERASE ENZYMES -
2 types of CHOLINESTERASE
Acetylcholinesterase (muscle synapse)
Pseudocholinesterase (plasma)
ESTERASE ENZYMES -
Non-specific esterases
RBC esterase
Paraxonase
Albumin Esterase
Common esterase dependent anesthesia drugs - Pseudocholinesterase (PChE)
Succinylcholine
Mivacurium
Ester local anesthetics (cocaine, procaine, chloroprocaine, tetracaine)
Neostingmine
Edrophonium
Common esterase dependent anesthesia drugs - Non-specific esterases (plasma)
Atracurium
Cisatracurium
Remifentanil
Clevidipine
Common esterase dependent anesthesia drugs - RBC esterases
Esmolol
Some people have atypical cholinesterase in their bodies what does this mean?
Will result in different metabolization rates of succinylcholine and ester LAs
Is atypical cholinesterase a pathologic condition?
No its an inherent difference among human beings- most common is Homozygote A (EaEa)
-tested via Dibucaine test
atypical cholinesterase - Homozygote A decreases enzyme activity by
> /= 70%, prolongs effects for 4-24 hours
Results in a Dibucaine test number of 16-30
Which test is used to determine if a person is slow to metabolize succinylcholine due to atypical cholinesterase?
DIBUCAINE INHIBITION TEST
What is dibucaine?
An amide local anesthetic which inhibits typical or usual pseudocholinesterase (PchE) but not atypical
Normal dibucaine number
80
Means that 80% of the ACh-esterase activity was inhibited by dibucaine
If dibucaine number is 20
the patient has an atypical enzyme since dibucaine did not inhibit the patient’s enzyme activity
If a patient experiences prolonged apnea following succinylcholine or mivacurium administration what must you differentiate between?
Atypical genetic variant of AChE or just low levels of AChE enzyme
-via Dibucaine test
Low dibucaine number + normal activity =
atypical enzyme and prolonged apnea
Normal dibucaine number + low activity =
Normal enzyme with low levels present and prolonged apnea
Normal dibucaine number + normal activity =
normal enzyme and amount (another reason for prolonged apnea must be investigated)
Low dibucaine number + Low activity =
atypical enzyme with low levels present and prolonged apnea
PChE variant - usual
Homozygote U (EuEu)
96% frequency
Normal enzyme activity
Duration of Succinylcholine is normal
Dibucaine test number- 70-80
PChE variant - Atypical
Homozygote A (EaEa)
0.3% frequency
Decreased enzyme activity by >/= 70%
Duration of succinylcholine is SIGNIFICANTLY prolonged 4-24 hours
Dibucaine number is 16-30
Succinylcholine side effects
Hyperkalemia
Dysrhythmias- hyperK related
Myalgia- from fasciculations
Myoglobinemia
Elevated intragastric pressure
Elevated IOP
Elevated ICP-from fasciculations and high CVP
MH
Masseter Spasm-followed by MH sometimes
Succinylcholine side effects - Hyperkalemia
Normally serum K+ increased by 0.5 mEq/L secondary to potassium leaking from the depolarized muscle
In patients with crush injuries, burns, denerving injuries, MH, K+ levels are much higher
Succinylcholine side effects- Dysrhythmias
From hyperK or ganglionic effects of succinylcholine
-Wide EKG complexed leading to arrest have been seen in children with dystrophin-deficient muscular dystrophies (duchennes, becker)
Succinylcholine side effects - Myalgia
Secondary to fasciculation even though some patients complain of muscle pain without having shown evidence of fasciculation
Succinylcholine side effects - Myoglobinemia
Rare complication after extensive fasciculation or MH
Succinylcholine side effects - elevated intragastric pressure
can occur from contractions of ab muscles d/t fasciculation
The elevation of intragastric pressure seen with succinylcholine are less significant than occur with CO2 insufflation during laparoscopic surgery
Succinylcholine side effects - Increase IOP
Ketamine + succinylcholine do this
-MOA unknown - seems related to contraction of ocular muscles during fasciculation from sux
Succinylcholine side effects - Malignant hypothermia
genetic predisposition
-MOA of succinylcholine triggering this is poorly understood
Succinylcholine side effects - masseter spasm
More often in kids than adults. Can be early sign of MH
so when succinylcholine is used with halothane vs when used with thiopental
Which patients is succinylcholine contraindicated in?
patients at risk for upregulation of ACh receptors
Ex-
· Upper or lower motor neuron defect
· Prolonged chemical denervation (i.e.) muscle relaxants, magnesium, clostridial toxins)
· Direct muscle trauma, tumor, or inflammation
· Thermal trauma/ Burns=
· Disuse atrophy
· Severe infection
Contraindications to succinylcholine
Hyperkalemia / hyperkalemia d/t renal failure (not the renal failure itself but the high K+
Burn patients -35% TBSA - 3rd degree
Severe muscle trauma
Neuro injury - paraplegia / quadplegia
Severe sepsis (abdominal)
Muscle wasting/ prolonged immobilization
MH
Denervating diseases
Duchenne muscular dystrophy- why we don’t give succinylcholine to kids; DMD can be undetected
Selected muscle disorders - in general patients with muscle disease shouldn’t receive
Children under 8 years old - only emergency situations (airway-kids don’t show typical signs of issues)
Genetic variants of pseudocholinesterase
Stains - (?) per nagelhout - ok
Allergy
Patients with muscle disease & succinylcholine
avoid sux
-patients with muscle disease will have increased sensitivity to non-depolarizing muscle relaxants and have lower dose requirements too
Cholinesterase enzymes:
Acetylcholinesterase (AChE)
known as true, specific, genuine, type 1
membrane bound glycoprotein
Cholinesterase enzymes:
Pseudocholinesterase (PChE)
known as plasma, serum, benzoyl, false, butryl, nonspecific, type 2
-has over 11 isoenzyme variants
Cholinesterase enzymes:
Pseudocholinesterase (PChE) locations
plasma
liver
smooth musc
intestine
pancreas
heart
white matter
Cholinesterase enzymes:
Acetylcholinesterase (AChE) locations
erythrocytes
nerve endings
lungs
spleen
gray matter
Neostigmine elimination half life
70-80 min
It takes 70-80 mins to eliminate the Ne Yo song stuck in my head
Edrophonium elimination half life
110 min - healthy pt
300 min - impaired renal function pt
-75% excreted by kindeys
Which do you give first, AChE inhibitor or anticholinergic/antimuscarinic?
Anticholinergic 1st
want to prevent the negative effects of the AChE inhibitor first
-could give neostigmine and robinul at same time technically
