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