The Basics Flashcards
Info obtained from M&M Notecards
Non depolarizing agents act as?
Competitive antagonists.
ACh receptors are bound but are incapable of inducing the conformational change necessary for ion channel opening.
Bc ACh is prevented from binding to it’s receptors, no end plate potential develops
Neuromuscular blocking agents are divided into two classes
De polarizing and blonde polarizing
De polarizing muscle relaxants act by?
Binding to ACh receptors, generating a muscle action potential.
These drugs are not metabolized by acetylcholinesterase, and their concentration in the synaptic cleft does not fall as rapidly, resulting in prolonged depolarization of muscle end plate
Phase I Block
the end plate cannot depolarize as long as the depolarizing muscle relaxant continues to bind to ACh receptors.
Phase II Block
after a period of time, prolonged end plate depolarization can cause ionic and conformational changes in the ACh receptor that clinically resembles that of non depolarizing muscle relaxants.
How does muscle denervation affect the NMJ?
it stimulates a compensatory increase in the number of ACh receptors and promotes expression of extra junctional ACh receptors:
leading to EXAGGERATED response to DEPOLARIZING muscle relaxants (w more receptors being depolarized)
but a RESISTANCE to NON depolarizing relaxants (more receptors that must be blocked)
How does Myasthenia Gravis affect the NMJ?
few ACh receptors lead to RESISTANCE to DEPOLARIZING relaxants and and INCREASED sensitivity to NON depolarizing relaxants
How does Eaton-Lambert Myasthenic Syndrome affect the NMJ?
decreased release of ACh
What is the definition of FADE with peripheral nerve stimulators?
Fade is a gradual diminution of evoked response during prolonged or repeated nerve stimulation, is indicative of a NONDEPOLARIZING blockade.
Adequate recovery correlates well with the absence of fade
What is Phase I Depolarization Block?
it does not exhibit fade during tetanus or TOF, and it does not demonstrate posttetanic potentiation.
If enough depolarizer is administered, the quality of the block changes to resemble a NONDEPOLARIZING block (Phase II block)
Succinylcholine: Mechanism of Action
DEPOLARIZING muscle relaxant (the only on in clinical use)
Succinylcholine: Dosage
1-1.5 mg/kg for intubation
Succinylcholine: Onset
30 - 60 seconds; typically lasts less than 10 minutes
Succinylcholine: Mechanism of Termination of Action
diffuses from NMJ, metabolized by psuedocholinesterases
Succinylcholine: Structure
two joined ACh molecules
Succinylcholine: two important drug interactions
CHOLINESTERASE INHIBITORS prolong the action of succinylcholine
NONDEPOLARIZING NMBA can antagonize a Phase I Block
Succinylcholine Contraindications
routine use of succinylcholine is relatively contraindicated in CHILDREN b/c of the risk of:
HYPERKALEMIA
Rhadbdomyolysis
Cardiac arrest from undiagnosed myopathies
Succinylcholine Side Effects:
CV: SCh stimulates ALL ACh receptors, which can lead to BRADY or TACHY. Brady occurs most frequently in children, but can occur in adults after second dose.
Fasciculations: denote the onset of paralysis
Hyperkalemia: normal m. releases K+ with SCh elevating the plasma K+ by 0.5 mEq/L. This can be life threatening with preexisting hyperkalemia or in pts who have suffered BURN injury or massive TRAUMA
M. Pains are sometimes noted post op
Elevation of ICP, Intragastic, and intraocular pressures
Masseter muscle rigidity occurs transiently
MH
NonDepolarizing NMBA are classified into which three categories?
Benzylisoquinilinium (tend to release histamine)
Steroidal (tend to be VAGOlytic)
Chlorofumarates
Nondepolarizers: what can prolong the block?
hypothermia, respiratory acidosis, hyokalemia, hypocalcemia, hypermagnesemia
Nondepolarizers: Hepatic Clearance
can impact PANCURONIUM and VECURONIUM
Nondepolarizers: Renal Excretion
significant in clearing DOXACURIUM, PANCURONIUM, VECURONIUM, and PIPECURONIUM
Atracurium is what type of nondepolarizer?
benzylisoquinoline
Atracurium: Metabolism and Excretion
undergoes ester hydrolysis from nonspecific esterase’s and HOFMANN ELIMINATION
(spontaneous b/d dependent on physiologic pH and temperature)
Atracurium: Dosage
0.5 mg/kg for intubation; intermediate duration
Atracurium: Side Effects
HISTAMINE release - hypotension, tacky, bronchospasm
LAUDANOSINE Toxicity - b/d of Hofmann elimination that can cause CNS excitation and is metabolized by liver
Prolonged action - at abnormal pH and temperature
Cisatracurium is what type of nondepolarizer?
Benzylisoquinoline
a stereoisomer of atracurium
Cisatracurium: metabolism and excretion
same as atracurium
undergoes ester hydrolysis from nonspecific esterase’s and HOFMANN Elimination
Cisatracurium: dosage
0.1 - 0.15 mg/kg for intubation; intermediate duration
Cisatracurium: Side Effects
Laudanosine Toxicity - significantly lower levels than with atracurium
Prolonged action - at abnormal pH and temp
Pancuronium is what type of nondepolarizer?
Steroidal
Pancuronium: Metabolism and Excretion
excretion is primarily renal (40%); limited liver metabolism and bile clearance
Pancuronium: Dosage
0.08 - 0.12 mg/kg for intubation; LONG duration
Pancuronium: Side Effects
HTN and TACHYcardia - caused by VAGAL blockade and SYMPATHETIC stimulation
Arrhythmias
Vecuronium is what type of nondepolarizer?
steroidal
Vecuronium: Metabolism and Excretion
excretion is primarily biliary and secondarily renal (25%)
limited liver metabolism
Vecuronium: Dosage
0.08 - 0.12 mg/kg for intubation; Intermediate duration
Vecuronium: Side Effects
can precipitate if administered with THIOPENTAL
possible prolonged duration in LIVER FAILURE
Active metabolites can lead to prolonged duration after long infusion
Rocuronium is what type of nondepolarizer?
steroidal
Rocuronium: Metabolism and Excretion
no metabolism;
excreted primarily by the liver and slightly by the kidneys
Rocuronium: Dosage
- 45 - 0.9 mg/kg IV for routine intubation
- 9 - 1.2 mg/kg IV for rapid intubation
1-2 mg/kg IM (onset, 3-6 min)
Intermediate duration at lower dose range
Rocuronium: Side Effects
prolonged action at higher dosage range
Gantacurium is what type of nondepolarizer?
Chlorofumarate
Gantacurium: Metabolism and Excretion
Cysteine adduction and ester hydrolysis
Gantacurium: Dosage
0..2 mg/kg for intubation with onset in 1-2 mins
Duration of action is 5-10 mins (can be accelerated by edorphonium or exogenous cysteine)
Gantacurium: Side Effects
Histamine release at higher dosages
Gancurium is available in the US? True or False
False
