NMBA Flashcards
Exam 3
1
Q
ACh is synthesized in nerve terminal by ____ ; _____ in presence of ________ ____________.
Each vesicle is referred to as a ______.
A
Choline
Acetyl coenzyme A
Choline acetyltransferase
Quantum
80% in vesicles
20% nonvesicle reserve
2
Q
What do you call the sm electrical potentials from Ach being released from vesicles?
What is the amt of mv?
What is the sum of this potential called?
A
Mepps (miniature end plate potentials
0.5-1
end plate potential
Action potential= all or nothing.
Threshold needs to be reached
3
Q
What is required for transmitter release of ACh to occur?
A
Ca and cAMP
5x more ach is released than needed to create action potentia
4
Q
What is ACh hydrolyzed to ?
What hydrolyzes it?
A
Choline; Acetate-diffuses away
Choline reuptake into nerve terminal
Acetylcholinesterase—ach destroyed less than 1ms after release.
5
Q
Where on the nAChR does ACh bind?
What type of change occurs to receptor and what does it lead to?
A
2 agonist on alpha subunit must bind
Ligand gated–entry of Neurotransmitters.
Conformational change –>Na channel open–>Na in–>depolarize membrane + action potential–>Action potential–>Ca released from sarcoplastic reticulum
6
Q
How many subunits on the post junctional nAChR?
Name them
A
5 (pentameric)
2-Alpha
1-Beta
1-delta
1-Epsilon
complex transmembrane glycoprotein core (250,000 daltons)
7
Q
What is a nAChR competitive agonist? Antagonist?
A
Sux
NDMB
8
Q
(True/False) Sux is hydrolyzed by Acetylcholinesterase?
Where does hydrolysis occur?
A
False
Plasma
Plasma cholinesterase/pseudo/butyrocholinesterese–Synthesized in liver
9
Q
How is sux action terminated?
A
Diffusion away from NMJ and to plasma.
Hydrolyzed by plasma cholinesterase there.
10
Q
when agonist bind to ___ subunits but do NOT cause a ________ change to open Na channel. This is called what?
A
Alpha
Conformational
Desensitization .
11
Q
Medications like Cocaine, abx, and Quinidine cause this..
A
Closed channel blockade
Drug reacts around mouth of channel, prevents passage of ions
12
Q
Closed channel blockade
A
Drug reacts around mouth of channel and prevents passage of ion.
13
Q
NDMB at large doses can lead to this.
A
Open channel blockade.
Drug enters channel but doesnt pass all the way (gets stuck)
Prevents flow of ions.
14
Q
What proliferates w/ decreased neural activity?
What is different about its structure?
A
Extrajunctional Receptors
Gamma instead of epsilon//stays open longer-allow for lg amt of K efflux.
15
Q
What pt population may have an increase in extrajunctional receptors?
A
Bedrest Burn Spinal cord Sepsis Trauma
Gamma instead of epsilon–open longer–more K efflux
16
Q
What are the extrajunctional receptors more sensitive to?
A
agonist-DMB–Sux
less (resistant) to NDMB(antagonist)–give More
17
Q
(True/False) Extrajunctional receptors are less sensitive to antagonist (NDMB) have to admin More of it
A
True
18
Q
Which VA potentiate the effects of NDMR the most?
A
Des > Sevo > Iso
19
Q
What are 2 functions of prejunctional receptors?
A
Inhibit release of Ach from presynapse
Stimulate production of Ach in nerve terminal
20
Q
Can you get post tetanic facilitation w/ sux?
A
no
21
Q
NMBA (5)
Structure
A
Ionized Water Soluble Limited Lipid solublility Placenta--No BBB--No
Quarternary ammonium groups
22
Q
For NMBA the Vd is influenced by what?
What is the Vd?
A
Age
Liver/renal disease
similar to ECF (14L)–water soluble
not highly protein bound.
23
Q
What are the long acting NMBA?
A
Pancuronium
24
Q
What are the intermediate acting NMBA?
A
Atracurium
Cisatracurium
Rocuronium
Vecuronium
25
IAs excluding _________ potentiate the effects of _______ via ______.
dosing should be ________.
Nitrous
NDMR
Ca channels.
Decreased
26
NMBA could be used to treat what conditions.
```
Intubation-facilitate
Laryngospasm-sux
O2 utilization-dec
Surgical conditions-enhance
Truncal rigidity w/opioids
```
27
For NDMR what is the recommended dose to facilitate intubation?
2xED95
28
What is the dose needed to produce ______ suppression of single twitch?
What is adequate depression for surgical relaxation?
95%
ED95
90% (3 responses abolished w/TOF)
29
The duration of action of Roc is longer in the adductor muscle of larynx than the adductor pollicis.
(True/False)
False
30
Do NMBAs cause the majority of anaphylactic reactions during anesthesia?
Yes
Sux & Roc
31
What group of NMBA are more likely to cause histamine release and what is this r/t?
Benzyquinoliniums
Atracurium
Cis--says in ppt but usually doesnt
Mivacurium
Tertiary amine
32
electrostatic attraction occurs at all cholinergic sites btw _________ and ________.
AChR ; NH4 groups
33
What influences the degree of CV effects?
| Maximal autonomic blockade occurs when?
Length of Carbon chain separating NH4+ groups.
NH4+ separated by 6Cs. (hexamethonium)
34
______ chains are more specific to nACHrs where?
Maximal NM blockade is achieved when?
Longer
NMJ
10Cs present (decamethonium)
35
Sux ED95 dose?
Intubation dose?
onset?
Duration?
0.25-0.5mg/kg
1mg/kg
30-60sec
5-10min
36
Depolarization is ________ and the depolarized membrane cant respond to additional agonist.
This is referred to as ________.
This can lead to this s/e
Sustained
Phase 1 blockade
Fasciculations
Sux--attaches 1 or 2 alpha subunits
37
Repeated doses of sux can cause ________
phase 2 blockade--? r/t desensitization, ion channel block or sux in cytoplasm.
38
Decreased contractile force in response to single twitch//sustained tetany w/ decreased amplitude//TOF ratio >0.7 and no PTF is seen w/ which NMBA..
Augmentation after anticholinesterase.
What type of blockade is this an example of?
Sux
Phase 1 blockade
39
```
TOF ratio <0.7//
Decreased amplitude and tetanic face//
Antagonized by anticholinesterase //
Abrupt onset, manifest as tachyphylaxis
is seen w/ _______.
```
Phase 2 blockade
Sux
Resembles NDMR
40
Sux is metabolized by what enzyme to _______________.
| If the enzyme level is below this percentage DOA will be prolonged.
plasma cholinesterase--made in liver
Succinylmonocholine/ choline--->Succinic Acid and choline
75%
41
What can lead to decreased levels of plasma cholinesterase?
```
Birth Control
Old
Burns
Pregnant
MAOI
Malnutrition
Esmolol
Neostig
Reglan
```
42
What is the test used for detection of atypical plasma cholinesterase?
Normal #?
Heterozygous?
Homozygous?
Dibucaine--Inhibits activity of normal plasma cholinesterase by:
80%
40-60-Modest (1:480)
20-NMB may last hrs(1:3200)
43
Myasthenia Gravis pt are ________ to Sux, r/t_________ in functional nAChRs, dose of sux would have to be ________.
resistant
Decrease
Increased
44
Which NMBA produces the greatest histamine release?
| What symptoms could manifest?
Sux--lg or rapid admin
Reduced BP--anaphylaxis rx-(sympathetic ganglia),
Bronchospasm
Face/Truncal flushing
45
Sinus Brady could be seen after admin of this medication in which population?
What causes this and how could it be pretreated?
Sux
Peds or admin of 2nd dose soon after 1st.
NDMR or atropine decreases incidence
Stimulation of cardiac postganglionic mAChRs
46
True/False
| Admin of smaller dose of Sux attenuates hyperkalemic response.
False
Pre treatment w/ NDMR doesnt protect against hyperK+
47
Myalgia is observed in what parts of the body most?
Which pt population is more at risk?
What can yo use as pretreatment/treatment?
Neck
Abdomen
Pharynx
Back
Young/healthy/athletes--more muscles
NDMR (defasiculating dose)
tx w/ NSAIDs
48
Sux can increase (3)?
ICP
IOP
Intra gastric pressure--risk aspiration--
increase HR, BP--sympathetic ganglia
49
Which NDMR is a mixture of 2 stereoisomers? Which configuration is 1/10 as potent as others.
Mivacurium-short acting
Cis-Cis
50
ED95-0.08mcg/kg
| Intubation 0.25 mg/kg
Mivacurium-short acting
51
Mivacurium
Onset:
DOA:
Hydrolyzed:
2-3min
10-20min
Plasma cholinesterase
52
ED95: 0.04 mg/kg
intubation: 0.2mg/kg
Cisatracurium
53
Intermediate acting NMBA onset; DOA
| Roc?
3-5min
20-35min (30)
Roc onset 1-2min
Atra/Cis/Vec
54
How is Cisatracurium metabolized?
| What are the metabolites?
Hoffman- at body ph and temp
Laudanosine-cleared renally
55
Which NMBA may be epileptogenic?
Atracurium--- a bisquaternary benzylisoquinolinium
laudonasine-CNS stimulant.
56
ED 95: 0.2 mg/kg
| Intubation 0.5mg/kg
Atracurium
57
Atracurium metabolism
Hoffman & hydrolysis non-specific plasma esterases
Produce laudanosine--renal clearance
58
Which NMBA causes an increased HR and decrease BP? at what concentration? What do you see at greater dose?
Atracurium
>2x ED95
Facial/truncal flush 3xED95
Histamine release
59
True/False
Decrease the dose in elderly pt receiving atracurium.
How about in Peds?
False--no change
Peds 1-6mo decrease 50%--more rapid recovery infants
60
Which NMBA is considered a CNS stimulant?
Atracurium
Increases MAC in animals
Epileptogenic
61
Which NMBA has the highest incidence among all periop drugs of anaphylaxis?
Roc
62
Sustained contraction of this muscle is common in children. What must you differentiate this from?
Masseter muscle (trismus)
Malignant Hyperthermia
Sux not recommended in children
63
rare, autosomal dominant disorder involving defective ________ receptors, which control release of _____ in _______ and leads to hypermetabolism.
ryanodine
Ca//Sarcoplasmic reticulum
Malignant hyperthermia--tx dantrolene
64
S/S Malignant Hyperthermia
```
Acidosis-metabolic
Tachy
Rhabdo
O2 consumption
Hyperpyrexia
Hypermetabolism
Hypercarbia
```
65
What percent blockade by NDMR doesnt produce evidence of blockade by single twitch?
70%
66
What percentage blockade is required to interrupt transmission of chemical signal?
80-90%
67
TOF w/ no fade & VC could be seen w/ what % of receptor blockade?
70%
| somewhat uncomfortable
68
Head lift 180 degrees for 5 sec, & sustained hand grip represents what percentage blockade?
50%
69
Tidal volume of 5ml/kg represents what percent blockade?
80%
70
What is indicative of 60% receptor blockade?
DBS//no fade
| Sustained tetany//no fade
71
A right shift of the dose response curve could be seen when?
Competitive antagonist
Desensitization
Agonist w/ lower receptor affinity
72
Tetanic stimulation before & after administration of a _______ dose of Sux is similar to the normal response to a _______
Large//NDMR
Post tetanic stimulation
Phase 2 blockade w/ sux
73
Which agent has a narrow autonomic margin of safety?
| Which agent has a wider autonomic margin of safety?
Pancuronium
Vecuronium//Cis//Roc
74
The difference btw the required dose for NM blockade and the dose for circulatory effects is known as?
autonomic margin of safety
75
CV effects are r/t what 2 things?
Histamine (prostacyclin release)
Antagonism of muscarinic and nicotinic receptors in ANS
76
Which medications enhance NDMR & DMR?
Abx-aminoglycosides (decrease prejunctional ACh by competing w/ Ca)
Antiarrhythmic
LocalAnesthetic
Lithium
77
Which medications only enhance NDMR?
Magnesium--esp Vec--inhibits Ca
| Diuretics--lasix Inhibit cAMP-->dec ACh output
78
Which medication inhibits cAMP leading to (inc or dec) in ACh output?
Lasix
Dec
enhances NDMR
79
Upper motor neurons located in ________. synapse w/ lower motor neurons on the ______ horn of the spinal cord. Which is the ____ matter on the _____/efferent.
Cerebral cortex
Anterior
Gray
Ventral
80
Single twitch is seen w/ blockade of the _________ nicotinic receptors
Post synaptic
81
Resting membrane potential is _____ mv. depolarization occurs w/ stimulation of ___ channels to open. Threshold is reached at ____mv and action potential created.
-90
Na
-45
82
Sudden influx of ___ is sufficient to _____ the membrane and create an ________.
Na
depolarize
action potential
Skeletal muscle contraction.
83
Opening of the channel pore w/ post junctional receptors converts and amplifies signal to _______.
electrical currents.
84
At large doses _____ may _____ the open receptor pore.
NDMR
Block
85
______ activate opening of the receptor pore when ____ are activated.
Activity is terminated by ______ away from the ____,
DMR--Sux
Both alpha subunits
Diffusion//NMJ
86
NM blockade w/ ______ occurs because the ______ post junctional membrane cannot respond to additional agonist.
DMR-SUX
| depolarized
87
Extrajunctional receptors are highly sensitive to ______ but less sensitive to _____.
agonist--sux
| antagonist--NDMR--Give more
88
W/ extrajunctional receptors you have to administer more/less of the NDMR?
More---less sensitive.
89
______ receptors located:
synapse-preganglionic and postganglionic PSNS & SNS
and _____.
Nicotinic
| NMJ
90
Muscarinic receptors located where.
Synapse postganglionic PSNS and end organ/tissue.
91
What is the primary pharmacologic effect of NMBA?
Block transmission of nerve impulses at NMJ
92
Vd influenced by 3 things?
Age
Renal/hepatic disease
14L-vd NMBA
93
VAs potentiate effects of NDMR via _____.
| Dosing should be ____.
ca channels
decreased
Des>Sevo>Iso
?decrease sensitivity of post junctional membrane to depolarization.
94
ED95 is dose necessary to produce _________ in response to ______ in 50% of population
95% suppression
| single twitch
95
What is the recommended dose for tracheal intubation?
| Surgical relaxation?.
2xED95
90% depression
96
The alpha subunits have at least one N that makes them
Quarternary ammonium group
97
Abnormal response to sux may be due to what?
Desensitization
ion channel block
or entry of sux into skeletal muscle cytoplasm
Phase 2 block
98
Dibucaine test is used to diagnose ____
atypical plasma cholinesterase
99
Increase in HR and BP occur w/ ____
Sux
| Sympathetic ganglia activity
100
masseter muscle (trismus) is common in ____ w/ this med
PEDS
Sux---Not reccommended
differentiate from MH
101
w/ NDMR _____ receptor blockade doesnt produce evidence of block w/ single twitch.
What amt of receptor occupation will?
70%
80-90%
102
Which medication is typically agonized by anticholinesterase meds?
DMR--Sux.
NDMR-antagonized
103
which med has a narrow autonomic margin of safety?
| Wider?
Pancuronium
vec/roc/cis
104
CV effects r/t ____ & ______. is from antagonism of ____ receptors
histamine & prostacyclin
muscarinic and nicotinic at ANS
105
males are _____ sensitive to NDMR than women
less
22% less required by woman.
106
Which NDMR increases HR, MAP, CO, increases in AV conduction and increased myocardial O2 consumed.
Pancuronium
antagonism cardiac muscarinic
ischemia in pt w/ CAD
107
Priming dose?
20% of ED95- NDMR
then after induction give the rest of INDUCTION dose (2xED95)--NDMR
108
Defasciculating
20% ED95 of NDMR before induction. then give larger dose of SUX
109
Cumulative effect w/ renal disease
Panc >Vec > Atra
110
Which med is unstable in solution
Vec--in powder needs reconstitute.
Does not antagonize mAChRs
´ Does not cause mast cell degranulation
111
Which med has similar potency in peds as adults but more rapid onset in infants. longer doa in infants.
Prolonged DOA elderly r/t lower clearance
Vec
112
Liver &; Renal disease can prolong w/
Vec--monoquartenary aminosteroid
| Roc--monoquartenary aminosteroid
113
Laudonasine is metabolite of _____.
Cleared _____
Has ____ effects.
Atracurium
Cisatracurium
Renally
CNS stimulant--increased MAC in animals
Epileptogenic--only Atra
Atra> cis
114
Infants 1-6 months need 1/2 of the adult dose w/ this med.
| Recovery is more ____ in infants.
Atracurium
Rapid
Old--no change in dose.
115
Rapid admin of this med = histamine --3xED95---
| 2xED95 w/ this med you gent increased HR and decreased BP.
```
mivacurium-3x
decreases map (transient)
```
Atracurium-2x//3x-facial/truncal flush
116
Which NMBA is excreted unchanged in Bile?
| & renal is >30%
Roc--monoquartenary aminosteroid
liver/renal can prolong function
117
Deacytylation occurs w/ which 2 meds. compound 50% as potent as parent.
Vecuronium--
Pancuronium--(20% hepatic & 80% unchanged in urine)---prolonged liver, renal, biliary, cirrhosis, old
118
resistance to NDMR is seen w/ _______
thermal injury
119
paresis/hemiplegia causes _______ w/ ______.
Resistance on affected side w/ NDMR
120
Ganglionic blockers
Delay onset and prolong DOA of NDMR
121
Dilantin
Decreases NDMR effect
122
Cyclosporin
Prolongs NDMR
123
Hyperkalemia
enhances DMR
Resistance to NDMR
124
Hypokalemia
Resistance DMR
enhance NDMR
