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220 Cards in this Set
- Front
- Back
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what nervous system do NMB work on
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the somatic nervous system
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what nervous system consists of the somatic NS and the ANS
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the peripheral nervous system (PNS)
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anesthesia is a lot about attentuating which nervous system
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ANS
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what is the fundamental unit of ALL branches and divisions of the ANS
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the neuron
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what does a neuron consist of
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*cell body
*axons and dendrites *telodendra |
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where in the neuron has little storage vessicles of Ach
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the dendrites
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what in the muscle has the Ach receptors
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the muscle fiber itself
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where is Ach stored
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in vesicles at the motor end plate
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what has to occur for muscle contraction to occur
|
enough mucsle fibers have to be stimulated
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Ach contains what that attaches to the cholinergic receptor
|
a POSITIVE charged quaternary ammonium
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is the cholinergic receptor positively or negatively charged
|
NEGATIVELY
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Ach is synthesized from what
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choline and acetate
|
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where is Ach stored
|
in vesicles at the motor end plate
|
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a quanta contains how many Ach
|
5-10 thousand
|
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how many quanta of Ach are released with EACH action potential
|
2-4 hundred quanta (1-4 million)
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how do we have basic muscle tone
|
some Ach quanta are released in the absence of nerve stimulation
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how is Ach metabolized
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by CHOLINESTERASE
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how quickly is Ach metabolized
|
in 1-3 thousandths of a sec
|
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Ach is released in what form
|
in quanta
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what is the Ach receptor made of
|
it is a pentameric protein (rosette) made of 5 subsets (2 alpha, 1 beta, 1 delta & 1 gamma)
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the gamma portion of the Ach receptor is called what for adults
|
EPISOLON
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the gamma portion of the Ach receptor is called what for fetuses
|
GAMMA
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what is the area for bonding within the nicotinic Ach receptor
|
the ALPHA subunits
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what is the negative part of the alpha subunit
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the anionic site
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what components does the ALPHA subunit of the nicotinic Ach receptor consist of
|
*anionic site (neg site)
*hydrogen bond donor site |
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Ach has to bind to how many of the ALPHA subunits to be activated
|
BOTH (2)
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Ach causes what to occur within the ALPHA subunit once it has bound
|
causes it to "twist and open"
|
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what is the ONLY depolarizing NMB used in the US
|
SUCCINYLCHOLINE
|
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how many of the ALPHA subunits does succinylcholine need to bind to in order to be activated
|
2 (BOTH)
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NON-depolarizing NMB need to bind to how many APLHA subunits to be activated
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only ONE
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NON-depolarizing NMB are agonists or antagonists
|
ANTAGONISTS
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depolarizing NMB are agonists or antagonists
|
AGONISTS
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how does Ach bind with the ALPHA subunit of the nicotinic Ach receptor
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Ach's cationic (+) ammonium binds to the anionic (-) receptor sites on the alpha subunit
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how does Ach "open" the channel of the nicotinic Ach receptor
|
by binding to TWO of the ALPHA subunits
|
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|
there are how many receptors across the cell membrane
|
1-10 million
|
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each subunit within the nicotinic Ach receptor contains what
|
4 helical domains labeled M1, M2, M3 and M4 that span the lipid bylayer
|
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which helical domain from the nicotinic Ach receptor subunit lines the ion channel
|
M2
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the ion channel of the nicotinic Ach receptor is equally permeable to what
|
Na+, K+ and Ca++
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what helical domain of the nicotinic Ach receptor subunit does the major "twisting" to make the conformational change
|
M2
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what does Ach diffuse across to bind to the receptor and ultimately make the muscle contract
|
the synaptic cleft
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what is acetylcholinesterase
|
(AchE)
it is an enzyme that rapidly breaks Ach down into acetate and choline |
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Ach is degraded how quickly
|
1-3000th of a sec
|
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where is Ach degraded
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in the synaptic cleft
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how is Ach "reformed"
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the byproducts acetate and choline are reuptaken by the motor end-plate and resynthesized and reused as Ach
|
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what size is AchE
|
*535 amino acids long
*over 60,000 daltons (AMU) |
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with NMB what equals greater control of the receptor site
|
a greater concentration
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what must a molecule have in order to bind to the nicotinic Ach receptor
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AFFINITY for the receptor
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what are the goals of NMB reversal
|
to increase Ach molecules to compete against NDMR this is done by blocking Ach's breakdown
|
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how is the breakdown of Ach prevented
|
via cholinesterase inhibitors
|
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what do cholinesterase inhibitors do
|
prevent cholinesterase enzymes from breaking down Ach anywhere in the body
*they are non-specific |
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what are the side effects of cholinesterase inhibitors
|
*bradycardia
*bronchospasm *N/V and abd cramping *diarrhea *salivation *blurred vision and miosis *urinary urgency |
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what attenuates the parasympathetic response that cholinesterase inhibitors produce
|
anti-cholinergics (anti-muscarinics)
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what are the side effects of anti-cholinergics
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*palpitations, tachycardia
*photophobia, mydrasis *blurred vision *constipation *diff with urination *dry throat/mouth *excitement, disorientation |
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what is the main NT for the PS system
|
Ach
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what are the GENERAL classes of NMB
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1-depolarizers
2-NON-depolarizers |
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what are the classes of NON-depolarizers
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1-isoquinolines
2-aminosteroidals |
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what is curare toxicans
|
an alkaloid extract from chondrodendron tomentosum
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in the amazon what are the cultural uses for curarae
|
*medicinal
*currency *status *hunting |
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curarae has what type of base structure
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isoquinoline
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when was the structure of curarae identified
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1935
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when was curarae 1st used in surgery
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1942 by Harold Griffith
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the muscle relaxant has what type of charge?
the Ach receptor has what type of charge? What type bond do they form when bound? |
*+ MR
*- Ach receptor *electrostatic bond |
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what is the active binding site on NMB
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ammonium group
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is curarae a depolarizer or non-depolarizer
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NON-depolarizer
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what does succinylcholine mimic
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Ach
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what are the main characteristics of ALL muscle relaxants
|
*they are highly ionized (which = low lipophlicity & high hydrophilicity)
*they are water soluble *have a LOW volume of distribution *do NOT cross the BBB, maternal barrier or GI |
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how do NON-depolarizers work
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*by competitive antagonism
*bind to Ach receptors but exert no effect (block action of Ach) |
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how do NON-depolarizers STOP working
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by diffusion away from NMJ site to site of metabolism or breakdown
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how are NON-depolarizing NMB categorized
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by duration
*short acting, intermediate acting and long acting |
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how long does a SHORT acting NON-depolarizer work
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5-20 min
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how long do INTERMEDIATE acting NON-depolarizing NMB work
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25-55 min
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how long do LONG acting NON-depolarizing NMB work
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60 min and >
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which class of NON-depolarizing NMB is most often used (short, intermediate or long acting)
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INTERMEDIATE acting
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how are NON-depolarizers metabolized
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in liver, kidney, plasma (by enzymes) or spontaneously
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are NON-depolarizers excreted in active or inactive forms
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BOTH
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what factors may affect the metabolism with NON-depolarizing NMB
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*organ insufficiency may affect it
*enzyme induction may INCREASE metabolism |
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what is up-regulation with NMB
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increase (up regulation) of Ach receptors
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which NMB are depolarizers
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*succinylcholine
*decamethonium |
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which NMB are NON-depolarizers
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*curare
*pancuronium *vecuronium *rocuronium *atracurium & cis-atracurium *mivacurium |
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which NON-depolarizing NMB is monquaternary
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vecuronium
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what is monoquaternary
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has ONE + ammonium
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what is bisquaternary
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has TWO + ammoniums
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which NON-depolarizing NMB is a bisquaternary
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pancuronium
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when categorizing NMB what things are examined
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3 things
1-action at recptor (agoinst vs antagonist) 2-base molecular structure of NDMR 3-duration |
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are depolarizers agonists or antagonists at the nicotinic receptor
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AGONISTS
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what is the mode of action for depolarizers
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they hold a sustained depolarization of the receptor making it unable to repolarize and blockade ensues
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what is the structure of succinylcholine
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it is 2 Ach molecules bound together
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how is succinylcholine metabolized
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by PLASMA cholinesterase NOT acetylcholinesterase that is found at the NMJ
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does succinylcholine last a shorter or longer duration than Ach?
why? |
*last longer
*b/c of it metabolism by PLAMSA cholinesterase and not acetylcholinesterase |
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how long does succinylcholine last
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5-10 min
|
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what is the structure of decamethonium
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it is a 10 chain hydrocarbon with ammonium groups for binding to alpha subunits
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what is NDMR duration dependent on
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metabolism/degredation and diffusion away from the NMJ
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curare and its derviatives have what type of base structure
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isoquinoline
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what class of NON-depolarizing NMB tend to release histamine and therefore cause BP decreases
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iosquinolines
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pancuronium and its derivates(roc and vec) have what base structure
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steriodal
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what group of NMB tend to INCREASE heart rate
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steroidal based NMB
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all NMB base structures have what added
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amine (N) groups
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isoquinolines are sometimes also called what
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benzylisoquinolines to account for the benzene functional group that is attached to the base isoquinoline
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what is SARS
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structure activity relationship
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what is CARS
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conformation activity relationship
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according to SARs all NMB are what type of compound
|
quaternary ammonium compounds
(4 carbon atoms attached to 1 nitrogen atom) |
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according to SARs all NMB contain at least one of these
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ammonium group
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according to SARs all NMB mimic what to exert relaxant properties
|
Ach
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Succinylcholine is a large/bulky molecule or a small/slender molecule
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small, slender
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how does succynylcholine activate the Ach receptor
|
by binding to BOTH (2) ALPHA subunits
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NON-depolarizers are large/bulky molecules or small/slender molecules
|
large/bulky
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are NON-depolarizers capable of activating the Ach receptor
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NO--they can bind to it but NOT activate it
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what in the NMB molecule is often an antigen for allergic responses
|
the ammonium group
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according to SARs what about NMB causes the s/e
|
its non-specificity for nicotinic Ach receptors
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the most common s/e exerted by pancuromium and succinylcholine is d/t what
|
attachement of those agents to MUSCARINIC Ach receptors
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what happens when pancuronium binds to the MUSCARINIC Ach receptor
|
it blocks vagus input and HR is increased
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all aminosteriodal NMB can do what to HR
|
INCREASE it
-most is seen with pancuronium -little seen with vecuronium |
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what type of molecules cause NON-depolarizing block
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patchycurares(thick)-bulky rigid molecules or onium heads
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what type of molecule causes a depolarizing block
|
leptocurares (slim)-slender molecules
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|
|
Respiratory acidosis
|
retention of CO2, always decreases PaO2
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the 10 atoms rule correlates with a linear distance of what
|
20 angstroms
|
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the more methyl groups a molecule has equals less or more potency
|
MORE
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the less methyl groups a molecule has equals less or more potency
|
LESS
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according to CARs what accounts for receptor blockade
|
conformational change (molecular shape changes)
|
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according to CARs molecules perfer what state?
this leads to? |
*LOW energy (at rest) states
*leads to seeking the shape that allows optimal "balance of energies" |
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according to CARs what distance is optimal to fit Ach receptor ALPHA subunits and cause binding or block
|
interonium distance of 20 angstroms
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a shorter distance than 20 angstroms leads to what
|
tends to ganglionic block (muscarinic block)
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longer distance molecules tend to do what
|
NMB (nicotinic block)
|
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what does the CARs Beers and Reich rules pertain to
|
distance between N+ and ether O (C-O-C)
*rule of 4.4A *rule of 5.9A |
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rule of 4.4A is what
|
states that that distance causes MUSCARINIC action
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rule of 5.9A is what
|
says that distance causes NICOTINIC action
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what are the charac of the "ideal" muscle relaxant
|
*NDMR
*rapid onset *short duration *predictable *void of s/e *termination NOT hepatic/renal *INACTIVE metabolites *non-toxic |
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is there an "ideal" muscle relaxant
|
NO
|
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what is Ach broken down into
|
acetate and choline
|
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what are the other names for acetylcholinesterase
|
specific cholinesterase or true cholinesterase
|
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what are the other names for plasma cholinesterase
|
pseudo or butyrylcholinesterase
|
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what is the only depolarizing NMB used in the US
|
succinylcholine
|
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what is the intubating dose for succinylcholine
|
1-1.5 mg/kg
|
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what has to be done with succinylcholine to retain its potency
|
refrigerate it
|
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what is the succinycholine molecule made of
|
2 Ach molecules linked together
|
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what NMB resemble and mimic Ach at the receptor
|
depolarizers
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what can occur after admin of succinylcholine
|
fasiculations during first massive non-synctal contractions of muscle fibers
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what is the action of succinylcholine
|
it causes a sustanined depolarization rendering the NMJ unable to conduct further impulses
|
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which NMB has a phase I and phase II block
|
succinlycholine
|
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what is a phase I block
|
sustained opening of receptor channels in depolarized post-junctional membrane canNOT respond further to Ach
|
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what is a phase II block
|
desensitized REPOLARIZED post-junctional membrane remains unresponsive to Ach
-occurs after large or repeated succinlycholine doses (unknown mech) |
|
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what determines if a pt is in a phase I or phase II block
|
a twitch monitor
|
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how is succinylcholine metabolized
|
in the PLASMA (not NMJ) by plasmacholinesterase
|
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how much of IV admin succinylcholine makes it to the NMJ
|
about 10%
|
|
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succinlycholine's duration is a component of what factor
|
its protection from PLASMA cholinesterase once it diffuses to the extravascular NMJ
|
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what is succinylcholine broken down into
|
*succinylmonocholine & choline after 1st breakdown
*then to succinic acid & choline after 2nd breakdown by PLASMA cholinesterase |
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what is the onset of succinylcholine (slow or rapid)
|
RAPID
|
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what is the duration of succinylcholine (short or long)
|
ULTRASHORT
|
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|
complete suppression of response to PNS in achieved how quickly with succinylcholine
|
in approx 60 sec
|
|
|
recovery to 90% muscle strength takes how long with succinylcholine
|
9 to 13 min
|
|
|
recovery from succinylcholine at NORMAL rate takes what factor
|
NORMAL butyrylcholinesterase (plasma cholinsterase or psedocholinesterase)
|
|
|
the short duration of succinylcholine is d/t what
|
rapid hydrolysis by butyrylcholinesterase into succinylmonocholine
|
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|
succinylmonocholine has what potency of succinylcholine
|
1/100th
|
|
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what is succinylmonocholine metabolized into
|
it is more slowly metabolized into succinic acid and choline
|
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what terminates succinylcholines actions
|
diffusion away from the NMJ
|
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where is butyrylcholinesterase synthesized
|
by the liver
|
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where is butyrylcholinesterase found
|
in the plasma
|
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what is butyrylcholinesterase
|
it is an enzyme that can metabolize succinylcholine, local anesthetics, esmolol and mivacron
|
|
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what would PROLONG succinylcholines activity
|
a decreased concentration of production of the enzyme butryrlcholinesterase
|
|
|
atypical butyrylcholinesterase (atypical plasmacholinesterase) may be a genetic mutation or caused by what other things
|
*liver dz
*malnutrition *severe anemia *organophosphate poisoning |
|
|
the measurement test for atypical butyrylcholinesterase generates what
|
a "dibucaine number"
|
|
|
what is dibucaine
|
a local anesthetic that uniquely inhibits plasmacholinesterase
|
|
|
dibucaine does what
|
can inhibit IV adminstered butyrylcholine metabolism if NORMAL plasmacholinesterase enzymes exist
|
|
|
what is not inhibited by dibucaine
|
ATYPICAL plasmacholinesterase
-so with its admin butyrylcholine will remain in the plasma |
|
|
with the "dibucaine number" more butyrlcholine in the plasma equals what
|
more ATYPICAL butyrylcholinesterase
|
|
|
a low inhibition of butyrylcholine's conversion to succinylmonocholine and choline is equal to what percent
|
20-30
|
|
|
a low inhibition of butyrylcholines conversion means what
|
a greater amt of ATYPICAL butyrylcholinesterase is present
|
|
|
a moderate inhibition of butyrylcholine's conversion is equal to what percent
|
50-60
|
|
|
a moderate inhibition of butyrylcholines conversion means what
|
some ATYPICAL and some normal (typical) butyrylcholinesterase is present
|
|
|
typical or NORMAL butyryllcholinesterase activity allows for what percent conversion of butyrylcholine
|
70-80
|
|
|
for homozygous TYPICAL plasma cholinesterase what is the genotype
|
UU
|
|
|
for homozygous TYPICAL plasma cholinesterase what is the dibucaine number
|
70-80
|
|
|
for homozygous TYPICAL plasma cholinesterase what is the response to succinylcholine
|
NORMAL
|
|
|
for heterozygous ATYPICAL plasma cholinesterase what is the genotype
|
UA
|
|
|
for heterozygous ATYPICAL plasma cholinesterase what is the incidence
|
1/480
|
|
|
for heterozygous ATYPICAL plasma cholinesterase what is the dibucaine number
|
50-60
|
|
|
for heterozygous ATYPICAL plasma cholinesterase what is the response to succinylcholine
|
prolonged to 4-8 hrs
(lengthened by about 50-100%) |
|
|
for homozygous ATYPICAL plasma cholinesterase what is the genotype
|
AA
|
|
|
for homozygous ATYPICAL plasma cholinesterase what is the incidence
|
1 in 3200
|
|
|
for homozygous ATYPICAL plasma cholinesterase what is the dibucaine number
|
20-30
|
|
|
for homozygous ATYPICAL plasma cholinesterase what is the response to succinylcholine
|
prolonged to 4 o 8 hrs
|
|
|
if succinlycholine is given with or after an anticholinesterase what happens to succinycholine
|
it is NOT broken down normally
|
|
|
what do you want to make sure of when giving a NDMB after succinylcholine
|
make sure the succinylcholine has metabolized prior to giving a NON-depolarizer
|
|
|
is low plasmacholinesterase activity a big concern in clinical practice
|
NO
|
|
|
large decreases in plasmacholinesterase activity does what to the DOA of succinylcholine
|
only moderately increases
|
|
|
with a 20% decrease in plasmacholinesterase activity what is the DOA with succinylcholine
|
3-9 min
|
|
|
how would the duration of succinylcholine be measured
|
by twitch monitoring
|
|
|
what are the s/e of succinylcholine
|
MANY
allergic rxns, CV effects, fasiculations, myalgias, hyperkalemia, myoglobinuria, sustained muscle contractions w/ myotonias, increased introcular-intragastric & intracranial pressures, MH, unmasked plasmacholinesterase def. |
|
|
allergic reactions to ALL of the NMB is d/t what
|
related to the positive ammonium group that is unique to ALL NMB
|
|
|
does succinylcholine release histamine
|
YES
-may lead to decreased BP, cause hives, wheezing & bronchospasm |
|
|
what are the CV effects that succinylcholine has
|
dysrhythmias
(brady arrythmias (sinus bradycardia & nodal juctional rhythm) and ventricular arrythmias) |
|
|
how does succinylcholine contribute to dysrhytmias
|
stimulates ALL cholinergic autonomic receptors
(nicotinic receptors on both S and PS ganglia and muscarinic receptors in the SA node of the heart) |
|
|
muscarinic (PS) effects of succinylcholine include what
|
severe bradycardia with junctional or ventricular escape beats
-asystole is possible |
|
|
cardiac arrest has occured when with succinylcholine
|
in apparently healthy children (60% incidence of death)
|
|
|
when is succinylcholine contraindiacted according to the FDA
|
in children 8 and younger unless it is an emergency situation
|
|
|
how does sinus bradycardia occur with succinylcholine
|
by stimulation of cardiac muscarinic receptors
|
|
|
when is sinus bradycardia more likely to occur with succinylcholine
|
with pts with predominant vagal tone such as children who have NOT received atropine
|
|
|
when is sinus bradycardia likely to occur in adults with admin of succinylcholine
|
when a second dose of succinylcholine is given approx 5 min after the first
|
|
|
how does nodal (junctional) rhythm occur with succinylcholine
|
by even greater stimulation of muscarinic receptors in the sinus node
-suppression of sinus mech leads to emergence of AV node as the pacemaker |
|
|
when is incidence of junctional rhythm greater with succinylcholine
|
after a 2nd dose
|
|
|
how can juctional (nodal) rhythm be PREVENTED with admin of succinylcholine
|
by previous admin of dTc (curare)
|
|
|
how do venticular dysrhythmias occur with admin of succinylcholine
|
succ lowers the threshold of the ventricle to catecholamine induced dysrhythmias
|
|
|
what medications/things (in addition to succinylcholine)may also lower the ventricular threshold for ectopic activity or increase the arrythmogenic effect of catecholamines
|
*digitalis
*TCA *MAOI *exogenous catecholamines *halothane |
|
|
what are fasiculations
|
non-synctal muscle fiber contractions
|
|
|
when is there a HIGHER incidence of fasiculations with succinylcholine
|
with young males and pts with muscular build
|
|
|
how can fasiculations associated with succinylcholine admin be lessened or eliminated
|
by PRIOR admin of NDNB
(makes less Ach receptors depolarized) |
|
|
myalgias or muscle pains with admin of succinylcholine is r/t what
|
fasiculations
|
|
|
what is a charac of myalgias with admin of succinylcholine
|
post-op muscle soreness
|
|
|
what is the incidence of muscle pain with admin of succinylcholine
|
0.2 to 89%
|
|
|
what type of pts have a HIGHER incidence of myalgias/muscle pain with the admin of succinylcholine
|
*younger pts
*muscular pts *women *ambulatory pts |
|
|
what type of pt is of extra concern regarding myalgias after admin of succinylcholine
|
pts with fibromyalgia
(may be predisposed) |
|
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what is a possible way that myalgias/muscle pain can be eliminated or lessen after admin of succinylcholine
|
pretreatment with NDMB
|
|
|
how is hyperkalemia caused by the admin of succinylcholine
|
massive sustained depolarization causes K+ to be released by the cells
|
|
|
what is the avg serum K+ increase with succinylcholine admin
|
0.5-1 mEq/dl
|
|
|
caution should be used with admin of succinylcholine when K+ is above what level
|
5.5
|
|
|
what are signs of increased K+
|
*tall spiked T waves
*ventricular ectopy |
|
|
what is the immediate tx for increased K+ caused by succinylcholine admin
|
*hyperventilation (resp alkalosis)
*Na bicarb |
|
|
what pts are more at risk for increased K+ with succinylcholine admin
|
burns, trauma, nerve damage, neuromuscular dz, intraabdominal infections > 1 wk, severe acidosis w/ hypovolemia
|
|
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does increased K+ with succinycholine admin usually cause dysrhythmias
|
NO
|
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when is increased K+ after admin of succinylcholine likely to cause dysrhytmias
|
*with renal failure pts
*pts with severe metabolic acidosis & hypovolemia |
