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125 Cards in this Set

  • Front
  • Back
What is the site of action for neuromuscular blocking agents?
Neuromuscular junction
Does neuromuscular blockade provide anesthesia, analgesia and paralysis?
No, it only provides paralysis
What type of channels are located at the neuromuscular junction?
Voltage gated calcium channels
What type of receptors are located on the muscle membrane at the neuromuscular junction?
Nicotinic cholinergic receptors
How many receptors must be activated for normal muscle contraction?
500,000
During depolarization, the nerve terminal releases ACh across the synaptic cleft, via what process?
Diffusion
The ACh receptor in the neuromuscular junction consists of what type and how many subunits?
Five protein subunits (2 alpha, a single beta, delta and epsilon subunits)
Which of those subunits are capable of binding with ACh molecules?
Alpha
ACh must bind with how many sites, for an ion channel to open?
Two
Describe how an end-plate potential is generated.
Cations flow through the open ACh receptor channel (sodium and calcium in; potassium out
A single vesicle may contain a quantum of ACh, how many molecules of ACh are in a quantum?
5,000 to 10,000
A decrease/increase in extracellular ionized calcium concentration causes the number of quanta to be released during a nerve impulse?
An increase in extracellular ionized calcium concentration
How many quanta are released by a single nerve impulse?
200
What makes the end-plate potential strong enough to depolarize the perijunctional membrane?
When enough receptors are occupied by ACh
________ channels within the perijunctional membrane open when what voltage is reached?
Sodium / threshold voltage or -45mv
End plate receptors open when _______ is applied.
ACh
Perijunctional areas of muscle membrane have a lower/higher density of sodium channels than other parts of the membrane.
Higher
When sodium channels open, calcium is released from what?
Sarcoplasmic reticulum
Intracellular calcium allows the contractile proteins______ and ______ to interact, bringing about a muscle contraction.
Actin / myosin
Decreased release of ACh is associated with what disease?
Eaton-Lambert myasthenic syndrome
Decreased number of receptors is associated with what disease?
Myasthenia gravis
ACh is rapidly hydrolyzed by acetylcholinesterase into what?
Acetate and choline
What percentage of ACh is hydrolyzed before it even reaches the nAChR's?
I50%
The NMJ contains 3 tyes of nicotinic cholinergic receptors - where are they located?
2 are postsynaptic on the skeletal muscle surface (1 junctional and 1 extrajunctional) and 1 is presynaptic
What processes are associated with up regulation of nAChRs?
spinal cord injury, CVA, burns, prolonged immobility, MS, Guillain-Barre syndrome, prolonged exposure to NMBDs
What are the two classes of neuromuscular blocking agents?
Depolarizing and nondepolarizing
Name depolarizing muscle relaxants and whether they are short-acting, intermediate-acting or long-acting.
Succinylcholine - short-acting
Name nondepolarizing muscle relaxants and whether they are short-acting, intermediate-acting or long-acting.
Mivacurium - short-acting / Atracurium, cisatracurium, vecuronium, rocuronium - intermediate-acting / doxacurium, pancuronium, pipecuronium - long-acting
What are the two chemical classifications of NDMR?
Aminosteroid and Benzylisoquinoline
Which class of muscle relaxants readily bind to ACh receptors?
Depolarizing
Are depolarizing muscle relaxants metabolized by acetylcholinesterase?
No
Why does use of depolarizing muscle relaxants result in prolonged depolarization of the muscle end-plate?
They are not metabolized by acetylcholinesterase and their concentration in the synaptic cleft does not fall as rapidly
Continuous end-plate depolarization causes muscle relaxation, why?
Because opening of the lower gate in the perijunctional sodium channels is time limited
Define a Phase I block
The end-plate cannot repolarize as long as the depolarizing muscle relaxant continues to bind to ACh receptors
Define a Phase II block
Prolonged end-plate depolarization can cause ionic and conformational changes in the ACh receptor
Which (depolarizing) phase block clinically resembles that of a nondepolarizing muscle relaxant?
Phase II block
Nondepolarizing muscle relaxants bind ACh receptors, but are incapapble of what?
Incapable of inducing the conformational change necessary for ion channel opening
When nondepolarizing muscle relaxants are used, how many sites must be blocked?
Only one alpha subunit must be blocked
How are depolarizing muscle relaxants reversed?
They are not reversed
How are depolarizing muscle relaxants metabolized?
They diffuse away from the neuromuscular junction and are hydrolyzed in the plasma and liver by pseudocholinesterase
What is the reversal of nondepolarizing muscle relaxants dependent upon?
Redistribution, gradual metabolism, and excretion of the relaxant by the body or administration of specific reversal agents that inhibit acetylcholinesterase enzyme activity
What may happen if you try to reverse a depolarizing muscle relaxant?
Depolarization blockade may be prolonged
These neuromuscular blocking drugs mimic the actions of acetylcholine.
Depolarizing neuromuscular blocking drugs
These neuromuscular blocking drugs interfere with the actions of acetylcholine.
Nondepolarizing neuromuscular blocking drugs
What two types of compounds are neuromuscular blocking drugs?
Benzylisoquinolinium or aminosteroid compounds
What is the most common way to determine the type, speed of onset, magnitude and duration of neuromuscular blockade?
Observe the skeletal muscle response that is evoked by a supramaximal electrical stimulus delivered from a peripheral nerve stimulator.
What nerve and muscle is most commonly used to assess the effect of neuromuscular blocking drugs?
Ulnar nerves and adductor pollicis
What does ED 95 mean?
Effective dose necessary to depress single-twitch depression by 95%. It determines potency
How does the presence of a volatile anesthetic effect ED95?
It is greatly decreased when compared to the value in the absence of these drugs
Neuromuscular blocking drugs affect muscles in what order?
Small, rapidly moving skeletal muscles before those of the abdomen / laryngeal>eyes>digits>diaphragm
The density of acetylcholine receptors is greater in (slow/fast) fibers.
Fast
Monitoring of what nerve/muscle stimulation more closely reflects the onset of neuromuscular blockade of the diaphragm?
Facial nerve
Which muscle when stimulated, is the better indicator of laryngeal muscle blockade?
Orbicularis oculi (Stoelting, p209)
The response evoked from a single-twitch stimulation reflects events at the (pre/post)junctional membrane.
Postjunctional membrane
The response to continuous stimulation of TOF reflects events at the (pre/post)synaptic membrane.
Presynaptic membrane
What characteristic makes neuromuscular blocking drugs highly ionized water-soluble compounds in physiologic PH and possess limited lipid solubility?
Their quaternary ammonium groups
Name lipid membrane barriers that neuromuscular blocking drugs cannot easily pass.
Blood brain barrier, renal tubular epithelium, gastrointestinal epithelium or placenta
What CNS effects are produced by neuromuscular blocking drugs?
None, they do not cross the blood brain barrier
The volume of distribution of neuromuscular blocking drugs is similar to what?
Extracellular fluid volume, about 200ml/kg (Stoelting, p. 209)
What is the intubating dose of a nondepolarizing muscle relaxant related to ED95?
2 times ED95
What is the percentage of suppression of single-twitch response usually considered clinical evidence of adequate drug-induced skeletal muscle relaxation for surgical working conditions?
90%
What is the analgesic equivalent to neuromuscular blocking drugs?
There isn't one, neuromuscular blocking drugs do not provide analgesia
Which neuromuscular blocking drug can treat laryngospasm and at what dose?
Succinylcholine at 0.1mg/kg IV
What are some clinical indicators of return of muscular strength?
Grip strength, ability to sustain head lift, following commands, vital capacity measurement and generation of negative inspiratory pressure
Which nondepolarizing neuromuscular blocking drug mimics the onset of Succinylcholine?
Rocuronium
Which nondepolarizing neuromuscular blocking drugs can produce significant decreases is systemic blood pressure?
Atracurium and Mivacurium via histamine release
Which nondepolarizing neuromuscular blocking drugs can produce significant increases in heart rate?
Pancuronium
Which nondepolarizing neuromuscular blocking drugs have no effect on circulation?
Vecuronium, rocuronium, cisatracurium, doxacurium and pipecuronium
If neuromuscular blocking drugs affect muscles in order of A,B,C,D... What order do they recover in?
D,C,B,A
What is usually the last muscle to be paralyzed and the first muscle to regain normal function with the use of neuromuscular blocking agents?
Diaphragm
If you were inadvertently injected with a nondepolarizing muscle relaxant while still awake, what symptoms would you have and in which order?
Difficulty in focusing, wakness in the mandibular muscles, ptosis, diplopia, and dysphagia
What improves with muscle relaxation?
Acuity of hearing
Which aminosteroid neuromuscular blocking drug is most closely related structurally to acetylcholine?
Pancuronium
Aminosteroid neuromuscular blocking drugs lack what type of activity?
Hormonal activity
What drugs or types of drugs interfere with neuromuscular transmission? (not muscle relaxants)
Aminophylline stimulates formation fo cAMP and facilitates neuromuscular transmission / Calcium channel blocking drugs (verapamil) interfere with neuromuscular transmission
What prevents sustained depolarization of the NMJ?
Rapid hydrolysis of acetylcholine
What events are associated with up regulation of nicotinic cholinergic receptors (nAChR)?
Spinal cord injury, CVA, thermal injury, prolonged immobility, prolonged exposure to neuromuscular blocking drugs, multiple sclerosis, Guillain-Barre syndrome
What events are associated with down regulation of nicotinic cholinergic receptors (nAChR)?
Myasthenia gravis, Anticholinesterase overdose, organophosphate poisoning
Where are extrajunctional cholinergic receptors located?
Anywhere over the entire postjunctional membrane
What two characteristics does Succinylcholine have that make it clinically superior for intubation purposes?
It produces intense paralysis rapidly and its effects are likely to wane before a preoxygenated patient becomes hypoxic
Describe the mechanism of action for succinylcholine.
SCh attaches to one or both of the alpha subunits of nAChRs and mimics the action of ACh, thus depolarizing the postjunctional membrane
Which is faster, the hydrolysis of ACh or SCh?
ACh
Depolarizing neuromuscular blockade is also referred to as what?
Phase I blockade
SCh is associated with leakage of K ions from the interior of cell into the serum, what changes do you expect?
A 0.5mEq/liter increase in serum potassium concentrations
What causes desensitization of neuromuscular blockade?
SCh > 2mg/kg IV, repeated doses or a prolonged continuous infusion
What is desensitization of neuromuscular blockade?
Postjunctional membranes that do not respond normally to ACh, even when the postjunctional membranes have become repolarized
Phase I/II blockade: Decreased contraction in response to single twitch stimulation
Phase I blockade
Phase I/II blockade: Decreased amplitude but sustained response to continuous stimulation
Phase I blockade
Phase I/II blockade: TOF ratio of >0.7
Phase I blockade
Phase I/II blockade: Absence of posttetanic facilitation
Phase I blockade
Phase I/II blockade: Augmentation of neuromuscular blockade after administration of an anticholinesterase drug
Phase I blockade
Phase I/II blockade: Can be antagonized with an anticholinesterase drug
Phase II blockade
Phase I/II blockade: Electrically evoked mechanical responses resemble those considered typical of neuromuscular blockade produced by nondepolarizing neuromuscular blocking drugs
Phase II blockade
Phase I/II blockade: Onset is often manifested initially as tachyphylaxis
Phase II blockade
Phase I/II blockade: Administering an anticholinesterase drug will enhance existing neuromuscular blockade
Phase I blockade
Phase I/II blockade: Administering an anticholinesterase drug will antagonize existing neuromuscular blockade
Phase II blockade
Duration of action of Succinylcholine?
3-5 minutes
Where is plasma cholinesterase synthesized?
Liver
What drugs cause a decrease in plasma cholinesterase activity?
Neostigmine, anticholinesterases, insecticides, metoclopramide, estrogen
Why might an obese patient need a larger dose of SCh?
Obese patients have greater plasma cholinesterase activity
These individuals have a decrease in functional ACh end-plate receptors, thus a decrease in the response to ACh?
Myasthenia gravis
If your patient received an appropriate dose of SCh and did not have return of normal muscle activity within 1-3hours, what are you suspicious of?
Atypical plasma cholinesterase
A local anesthetic with an amide linkage, inhibits the activity of normal plasma cholinesterase by approximately 80%.
Dibucaine
What is a normal plasma cholinesterase enzyme number? And what does it reflect?
80, it reflects 80% inhibition of enzyme activity
Dibucaine number of 20
Homozygous
Dibucaine number of 40-60
Heterozygous
What does a dibucaine number represent?
The quality of cholinesterase enzyme (ability to hydrolyze SCh) and not the quantity of the enzymes in the plasma
If you had a healthy patient who recently experienced liver trauma with significantly decreased liver function, would your dibucaine number be higher or lower?
It would not change (there would be a decrease in plasma cholinesterase activity which would prolong the action of SCh)
What are side effects of SCh?
Cardiac dysrhythmias, hyperkalemia, myalgia, myoglobinuria, increased intragastric pressure, increased IOP, increased ICP, sustained skeletal muscle contractions
What can prevent or attenuate the occurrence of physical side effects of SCh?
Administration of nonparalyzing doses of a nondepolarizing neuromuscular blocking drug
What are s/e when SCh act on cardiac muscarinic cholinergic receptors?
Sinus bradycardia, junctional rhythm, sinus arrest
When are cardiac dysrhythmias most likeley to occur in relation to SCh?
After a second dose of SCh is administered approx. 5 minutes after the first dose
What are the metabolites that are suspected in the role of SCh and cardiac dysrhythmias?
Succinylmonocholine and choline
Is atropine the appropriate treatment for SB from a second dose of SCh?
No
Hyperkalemia may occur after administration of SCh to what kind of patients?
Muscular dystrophy, burns, denervation leading to skeletal muscle atrophy, sever skeletal muscle trauma, upper motor neuron lesions, severe abdominal infections
What is the most common form of muscular dystrophy in male children?
Duchenne muscular dystrophy
What s/e are associated with SCh when administered to male children with undiagnosed myopathies?
Rhabdomyolysis, hyperkalemia and cardiac arrest
What muscles are most prominently effected by postop myalgia when SCh has been administered?
Neck, back, and abdomen
Myoglobinuria occurs in adults or children post SCh?
Children
What causes the increased intragastric pressure associated with SCh?
Skeletal muscle fasciculations
What is the fear of increased IOP with SCh and open eye injuries?
Extrusion of global contents
Increased IOP is associated with (increased/decreased) choroidal blood volume and central venous pressure and deepening of the anterior chamber and (decreased/increased) resistance to outflow of aqueous humor.
Increased / increased
Masseter muscle rigidity is a sign of what?
Normal response to SCh or associated with the deveopment of MH
Sustained skeletal muscle spasm may accompany the administration of SCh to patients with what diseases? And may interfere with what?
Myotonia congenita or myotonia dystrophica / Ventilation of the lungs
Act by combining with nicotinic cholinergic receptors.
Nondepolarizing neuromuscular blocking drugs