Pharm Quiz #4 Flashcards
(161 cards)
1
Q
How does the number of twitches correlate with degree of neuromuscular block?
A
T4 disappears at 75% depression
T3 disappears at 80-85% depression
T2 disappears at 90% depression
Twitch suppression of 90% would equate to a TOF count of 1 or less
2
Q
When is reversal of residual NMB safely achieved?
A
When TOF is => 3 twitches
3
Q
Traditionally, it had been accepted that a TOF ratio of 0.7 or greater was an indication of adequate reversal however……..
A
it is now that that a TOF ratio of 0.9 should be achieved before tracheal extubation(at least 3 twitches)
4
Q
Is TOF more useful monitoring depolarizers or non-depolarizers?
A
non-depolarizers; with depolarizers, each twitch is decreased equally in size with NO fade
5
Q
What is the normal set time for tetanic stimulation?
A
5 seconds
6
Q
In non-paralyzed skeletal muscle, tetanic response is…..
A
maintained tetanic contraction
Once given a non-depolarizer, the muscle shows fade and is unable to sustain muscular contraction
7
Q
The degree of fade corresponds to the…..
A
degree of NMB
8
Q
What limits the use of Tetanic stimulation?
A
pain
9
Q
Tetanus fade is the effect of non-depolarizing agent on _____ nerve membranes.
A
presynaptic
10
Q
With non-depolarizers, what contributes to fade during tetanic stimulation?
A
competitive block of presynaptic receptors that decreases mobilized and released acetylcholine
11
Q
Is fade seen with tetanic stimulation during partial depolarizing block?
A
no
12
Q
Single twitch nerve stimulations gives what information?
A
Post synaptic/junctional information(muscle side)
13
Q
Tetanus and TOF gives what information?
A
Pre synaptic/junctional membranes
14
Q
Tetanic stimulation should not be repeated for how many minutes?
A
6 minutes
*Tetanic stimulus affects NMJ of stimulated nerves for a significant time
15
Q
What drug class is acetylcholine?
A
Quaternary ammonium ester
16
Q
How many molecules are in a quanta?
A
1000 molecules
17
Q
First twitch is only accurate if ____ seconds have elapsed since previous stimulation.
A
10
18
Q
What is the main disadvantage of tetanus?
A
Post-tetanic facilitation(pain)
19
Q
Increased sensitivity to non-depolarizers due to extra juctional proliferation is seen in what type of patients?
A
Paraplegia/quadriplegia
20
Q
Greater than 30% body surface area burns acquire non-depolarizing NMB resistance. Explain
A
Begins 10 days after injury
Peaks at 40 days
Declines after 60 days
21
Q
What are the cardiovascular effects of non-depolarizers?
A
Actions from histamine release
Effects at cardiac muscarinic receptors
Effects at autonomic ganglia nicotinic receptors
Rarely has clinical significance
22
Q
Non-depolarizing NMB have enhanced activity due to perioperative drugs including….?
A
Volatile anesthetics(enhance effects) Aminoglycosides** Local anesthetics Anti-dysrhythmics Diuretics Mg++ Lithium Ganglionic blockers(arthenand)
23
Q
Non-deplarizing NMB effects are altered by what?
A
Hypotension Acidosis/alkalosis Serum K levels Adrenocortical dysfunction Thermal injury Allergic reactions
24
Q
Non-depolaring NMB enhancement is greatest with(3) and least with(2)?
A
Iso, Sevo, Des
Nitrous, Opioids
25
Non-Depolarizing NMB enhancement by VA leads to what?
probable volatile anesthetic induced depression of CNS-decreased skeletal muscle tone
26
By what function do Aminoglycosides enhance non-depolarizing NMB?
due to pre-junctional release of acetylcholine and decreased post-junction membrane sensitivity
27
Will there be any TOF or single twitches noted with profound non-depolarizing NMB?
no
28
With profound NMB, what is the best reversal?
time
29
What is the characteristics of Post-tetanic count?
5 second tetanic stimulus at 50 hz administered, followed 3 seconds later by single twitches
*response seen in the early stages of recovery, before TOF reappears*
30
After tetanic stimulus, acetylcholine synthesis and mobilization continues this leads to......
there is increased acetylcholine causing enhanced response to subsequent single twitch stimulation
*number of post-tetanic twitches indicates when first twitch of TOF reappears*
31
What is the mode of action of non-depolarizers?
Bind to post-junctional nicotinic cholinergic alpha subunit receptors sites without any activation of ion receptor channels
32
Is there any evidence of NMB with occupancy of < 70% of nicotinic cholinergic receptors?
No evidence of block by single twitch test
33
Neurotransmission fails when ___-___% of alpha subunit post-junctional nicotinic cholinergic receptors are blocked.
80-90%
34
What are the characteristics of non-depolarizing NMB?
- decreased response to single twitch
- fade during tetanus
- TOF ratio less than 0.7
- Post-tetanic potentiation
- potentiation of other non-depolarizing NMB
- antagonism by anti cholinesterase drugs
- NO fasciculations
35
Skeletal muscle response is ___ or ___.
all or nothing;
Skeletal muscle fibers contract maximally or not at all.
Therefore, when twitch response is decreased, some fibers are normally contracting & some are completely blocked.
36
There is no detectable block until how much of the receptors are occupied?
75-85%
37
Paralysis is complete at how much receptor occupancy?
90-95%
38
Adequate muscle relaxation corresponds to a narrow range of how much receptor occupancy?
85-90%
39
What is the definition of the ED95 of a drug?
dose producing 95% single twitch depression
40
First twitch accurate only if.......
10 seconds have elapsed since previous stimulation
41
Disappearance of 4th response after TOF stimulation correspond to.....
70-75% single twitch depression
42
With TOF, four successive stimuli are delivered at?
2 Hz every 0.5 seconds
*immediately available stores of acetylcholine are depleted and amount released by nerves decreases with successive stimuli
43
During _____ NMB TOF does not fade.
depolarizing
*the height of all the four twitches decreases simultaneously*
44
With non-depolarizing NMB what is the response of TOF with increasing degree of block?
- The twitches in TOF progressively fade starting with the fourth and one by one eventually disappear.
- The ratio of the height of the fourth response to the first has been defined as the TOF ratio.
- In the absence of non-depolarizing block, the T4/T1 ratio is approximately one.
45
There is no need for a control measurement before using TOF to measure relaxant?
true
46
Is there post-tetanic facilitation with TOF?
No; so can be repeated every 10 - 12 seconds
47
With tetanus, fade is first noted at what % receptor occupancy?
70%
48
What is the main disadvantage of post tetanus?
post-tetanic facilitation(very painful)
*less useful than TOF*
49
With hemiplegia, resistance to non-depolarizers develops with how many days?
2-3 days
May be due to central inhibition
50
Should the unaffected or affected side be monitored with those with hemiplegia?
the unaffected side
51
What response to non-depolorizers will be seen to those with Parkinsons and multiple sclerosis?
Normal response to NMB monitoring
52
Those with myotonia and muscular dystrophies have what response to non-depolarizers?
mostly normal response
53
What effect does succinylcholine given for intubation have on twitch suppression produced by non-polarizing NMB dosing?
increases twitch suppression even when succinylcholine effects have gone
54
What is the definition of autonomic margin of safety?
difference between NMB dose and dose producing circulatory effect
*ED95 dose of pancuronium producing NMB also produces increased HR, so autonomic margin of safety is low
55
Non-depolarizing NMB enhancement by volatile agent is caused by?
probable volatile anesthetic induced depression of CNS--->decreases skeletal tone as an additive effect
56
How does the co-administration of aminoglycosides effect non-depolarizing NMB function?
decreased pre-junctional release of acetylcholine & decreased post-junction membrane sensitivity to acetylcholine
***reversal of non-depolarizing of NMB less predictable on patients receiving aminoglycosides***
QUIZ QUESTION
57
Are intermediate non-depolarizers most or less expensive than succinylcholine or pancuronium?
more expensive
58
Do intermediate non-depolarizers have CV effects?
minimal to absent
59
What is the drug class of Vecuronium?
Monoquaternary aminosteroid non-depolarizer
60
What is the onset of vecuronium?
3-5 minutes
61
What is the duration of action of vecuronium?
20-35 minutes
62
What is the structure of vecuronium?
Structurally its pancuronium without the quaternary methyl group in the A-ring of the steroid nucleus
63
What is the intubating dose of vecuronium?
0.1 mg/kg
64
What is the physiologic effect of the absence of quaternary methyl group in vecuronium?
it reduces the acetylcholine-like character, decreasing vagolytic effects by 95%
65
Vecuronium undergoes _____ metabolism & _____ excretion.
hepatic, renal
66
Is vecuronium more or less lipid soluble than pancuronium?
More lipid soluble which facilitates its entrance into hepatocytes.
67
What are the 3 metabolites of vecuronium?
1. 3-desacetyl vecuronium- 1/2 as potent as vecuronium
2. 17-desacetyl vecuronium- 1/10 as potent as vec
3. 3,17-desacetyl vecuronium- 1/10 as potent
68
How much of the vecuronium dose is present in the liver 30 minutes after administration?
50%
69
What aids in vecs rapid reduction in plasma concentration and short duration of action?
Extensive hepatic uptake
70
Is elimination 1/2 time prolonged in ESRD with vecuronium?
yes
71
Doubling the vec dose to _____ mg/kg prolongs duration of action & elimination 1/2 times in hepatic dysfunction patients.
0. 2 mg/kg
| * Vecuronium doses of 0.1 mg/kg not associated with prolonged duration of action in hepatic dysfunction
72
What acid base changes can be seen with vecuronium?
hypoventilation occurring in the post period may enhance residual neuromuscular blockade from vec
73
Does vec have a small or large Vd?
large Vd due to significant tissue uptake
74
With single doses of vec, plasma {} decline rapidly due to ?
redistribution
* with repeated doses, peripheral compartments become saturated & redistribution is limited*
* Cumulative effects are present, less then pancuronium*
75
How does onset of action/duration of action of vec in children compare to adults?
- onset of action-more rapid in infants than adults
- duration of action-longest in infants/shortest in children
*infants high CO speeds onset of blockade-immature neonate enzyme systems and greater Vd lengthen duration of action*
76
Why would you decrease vec dosing in the elderly?
- lower plasma clearance from reduced renal/hepatic blood flow
- lower microsomal enzyme activity
*recover of single twitch response prolonged in elderly with vec infusions-with single dose vec, elimination 1/2 time and dose responses are no different in the elderly*
77
Are there any effects on the newborn when vec is given to the OB patient
no-insufficient {} cross placental barrier
78
How does vec affect the patient over 130% of ideal body weight?
duration of action may be prolonged
79
Unlike Succ, vecuronium does not(2).
1. does alter intraocular pressures
| 2. does not trigger MH
80
What is the drug classification of Rocuronium?
Monoquaternary aminosteroid non-depolarizer
81
What is the onset and DOA of rocuronium?
onset-1-2 minutes
| DOA- 20-35 minutes
82
What is the structure of Rocuronium?
like vecuronium except rocuronium has a hydroxyl group rather than an acetyl group on the A-ring of the steroid nucleus
83
What contributes to the speed of onset of Rocuronium?
lack of potency--->more drug available to bind to receptors
84
The onset of max doses(3-4xED95) of Roc resembles ____?
succinylcholine;Rocuronium the only non-depolarizer that serves as an alternative to succinylcholine for RSI
85
Which set of muscles are more resistant to roc?
Laryngeal muscles more resistant to roc than adductor pollicis muscles
86
Since laryngeal muscles are resistant to rocuronium, large doses of rocuronium will resemble _____ at adductor pollicis but _____ at laryngeal adductors.
succinylcholine; delayed
* complete suppression of twitch response @ adductor pollicis does NOT confirm laryngeal & diaphragm paralysis*
* Initiating laryngoscopy @ peak laryngeal muscle paralysis may result in diaphragm movement during tube placement*
87
For best intubation conditions monitor _____, for best return of breathing monitor _____.
obicularis occuli; adductor pollicis
88
How is rocuronium cleared by the body?
up to 50% exerted unchanged in bile
89
How does rocuronium affect ESRD patients?
will have longer DOA
90
How does rocuronium affect patients with impaired liver function?
longer DOA especially with infusions and multiple doses due to their larger Vd.
*Elderly have similar onset but longer DOA due to impaired hepatic clearance*
91
Does roc have histamine release or vagolytic effects?
no histamine release, only a slight vagolytic effect
92
What is the drug classification of Cisatracurium?
Benzylisoquinolinium non-depolarizer
93
What is the intubating dose of Cisatracurium?
0.1 mg/kg
94
What is the onset of action and duration of action of Cis?
OoA- 3-5 minutes
| DoA- 20-35 minutes
95
How does Cisatracurium compare to Atracurium?
has a NMB profile similar to atracurium except a slightly lower onset and much lower histamine release.
*Cis is one of 10 stereoisomers of Atracurium, accounting for 15% of the mixture*
96
Is the rate of recovery of Cis influenced by prolonged infusion?
no; NM block is easily maintained by constant rate infusion without diminishing over time.
*NO cumulative effects!*
97
What is the principle mechanism of degradation of Cis and what is the byproduct?
Hoffman elimination
98
What are the two byproducts of the degradation of Cis?
at physiologic pH and temp, it forms laudanosine and a mono quaternary acrylate
99
What are the two ways Cis is cleared from the body and the percentages related?
77% clearance by Hoffman elimination
| 16% clearance by the kidneys
100
Unlike atracurium, _____ _____ do NOT help cisatracurium clearance.
plasma esterases
101
Is there any alterations in the NMB profile of cisatracurium with ESRD?
no
*pharmacokinetics minimally altered by advanced age-only slightly slower onset is noted*
102
Cisatracurium metabolites are _____ at the NMJ.
inactive
103
Plasma {} of principle metabolite laudanosine, are _____ with cis due to greater potency.
lower
104
What is the only depolarizing NMB?
Succinylcholine
105
What is the OoA and the DoA of Succinylcholine?
DoA 3-5 minutes
| OoA 30-60 seconds
106
What is the intubating dose of Succinylcholine?
1 -1.5 mg/kg
107
What is the mechanism of action of Succinylcholine?
- attaches to alpha subunits of nicotinic cholinergic receptors
- mimics action of acetylcholine
- depolarizes the post-junctional membrane
108
Compared to acetylcholine, _____ of succinylcholine is _____, resulting in _____ depolarization- receptor ion channels remain open.
hydrolysis, slow, sustained
109
How does succinycholine cause NMB?
occurs because depolarized post-junctional membranes can not respond to new acetylcholine release
*depolarizing block = Phase I block*
110
How is succinylcholine degraded?
degraded by pseudocholinesterase, a plasma cholinesterase(as opposed to acetylcholinesterase)
*Hydrolysis by pseudocholinesterase much slower than acetylcholine by acetylcholinesterase*
111
In succinylcholine, sustained receptor ion channel opening and depolarization of post-junctional membranes causes _____ leakage from cell interiors. This causes an increase in what ion, and by what margin?
potassium, 0.5 mEq/L in serum K+
*****hyperkalemia is contraindicated in succinylcholine*****
112
Succinylcholine dosing with doses > 2mg/kg, repeated doses or succinylcholine infusions may cause.....
post-junctional membranes that will not respond to succinylcholine(phase II block)
*mechanism for desensitization NMB unknown, hence the name phase II block which docent imply a mechanism*
113
What are the characteristics of a phase I block?
- reduced response to single twitch
- reduced but sustained response to tetanus
- TOF ratio > than 0.7
- no post-tetanic facilitation
114
Succinylcholine's short DoA is due to?
hydrolysis by plasma cholinesterase made in the liver
115
What is the initial metabolite of succinylcholine?
succinylmonocholine---> very weak neuromuscular activity
116
What is succinylmonocholine broken down to?
succinct acid and choline
117
Plasma cholinesterase capacity is _____ - most succinylcholine _____ before reaching neuromuscular junction.
huge, hydrolyzed
118
Plasma cholinesterase not found in large amounts at the NMJ, so ending of succinylcholine NMB due to.....?
diffusion away from neuromuscular action
119
Plasma cholinesterase affects succinylcholine DoA by....?
controlling amounts hydrolyzed before reaching NMJ
120
Succinylcholine rapidly hydrolyzed by plasma cholinesterase to?
succinylmonocholine
121
Succinylmonocholine metabolized to?
succinic acid and choline(QUIZ QUESTION)
*10% of the succinylcholine excreted unchanged in the urine*
122
With succinylcholine, depolarization may be observed as?
fasciculations
*subsequent NM transmission inhibited as long as adequate {} of succinylcholine remain @ receptors*
123
What is the onset of paralysis and DoA of Succinylcholine?
< 1 minute and DoA= 4-6 minutes
124
When both alpha subunits are bound =?
| when pretreatment used only 1 bound =?
fasiculations
| no fasiculations
125
What are two affects of longer effects of succinylcholine?
- higher doses cause the effects to last somewhat longer
- when plasma levels of cholinesterase are greatly diminished or an atypical form of cholinesterase is present paralysis may last longer
126
What is the IV/IM pediatric dose of succinylcholine?
IV=2 mg/kg
| IM=3-4 mg/kg
127
The onset of succinylcholine given IM is usually observed in about?
2-3 minutes
128
IV bolus succinylcholine in infants or children may result in?
profound bradycardia or asystole
129
The incidence of bradycardia in children is higher following a?
second dose of succinylcholine
130
The occurrence of bradyarrhythmias in infants/children may be reduced by?
pretreatment with atropine
131
What are 4 conditions that are contraindications of Succinylcholine and why?
1. major burns
2. multiple trauma
3. extensive denervation of skeletal muscle
4. upper motor neuron injury
*Succinylcholine administration may result in SEVERE HYPERKALEMIA which may result in cardiac arrest*
132
Risk of hyperkalemia in patients with the 4 contraindications _____ over time and usually peaks at day ___ to ____ after the injury.
peaks; 7 to 10
*risk is dependent on the extent and location of the injury, precise time of onset and duration of the risk period are not known*
133
What are the adverse effects of succinylcholine?(8)
- dysrhythmias
- hyperkalemia
- myalgia
- myoglobinuria
- increased intragastric pressure
- increased intraocular pressure
- increased ICP
- sustained skeletal muscle contractions
134
All of the adverse effects of succinylcholine may be minimized with pre-treatment except for?
hyperkalemia
135
What are 10 adviser effects of succinylcholine?
- hypotension
- hypertension
- initial muscle fasciculations
- excessive salivation
- MH
- rare allergic reactions
- phase II block
- anaphylaxis
- jaw rigidity--->one of the first signs of MH with such
- rhabdomyolysis with possible myoglobinuric renal failure
- rash
- prolonged resp depression or apnea
136
Pre-treatment with non-depolarizers may prevent dysrhythmias, myalgia, increased intragastric pressures, increased intraocular pressures, but not ___.
hyperkalemia
137
Succinylcholine is associated with MH. Risk increases with co-administration of volatile anesthetics. MH presents as?
- intractable spasms of the jaw muscles
- generalized rigidity
- increased O2 demands
- tachycardia
- tachypnea
- profound hyperpyrexia
138
Incomplete jaw relaxation or masseter muscle rigidity occurs most often with?
peds-not necessarily abnormal
- may occur in up to 4% of peds population
- the question is normal variant or MH?
139
Sustained muscle contraction may also occur with these two conditions which may make ventilation impossible when administering Succ to the pediatric population.
1. myotonia congentia
| 2. myotonia dystrophia
140
Succinylcholine should be administered with GREAT CAUTION to patients suffering from(2)?
In these circumstances succinylcholine may induce(2).....due to?
- electrolyte abnormalities
- DIGOXIN TOXICITY
- serous cardiac arrhythmias
- or cardiac arrest
-hyperkalemia
141
Does non-depolarizer pre-treatment prevent hyperkalemia?
NOPE
142
Succinylcholine has fallen out of favor in part due to the small % of male peds patients with undiagnosed _____, typically _____.
With these undiagnosed conditions, what 3 adverse events are possible if given succinylcholine?
- myopathies
- Duchenne MD
- rhabdomyolysis
- hyperkalemia
- cardiac arrest
143
Succinylcholine has no direct effect on the myocardium(t/f).
true
144
Succinylcholine stimulates(2).......which can cause changes in cardiac rhythm including cardiac arrest.
- autonomic ganglia
| - muscarinic receptors
145
Changes in cardiac rhythm may result from(2)......., particularly in children.
- vagal stimulaiton
| - hyperkalemia
146
The effects upon the human heart by succinylcholine may be enhanced by?
halogenated anesthetics
147
What 3 dysrhythmias may occur with succinylcholine dosing?
- sinus brady
- junctional rhythms
- sinus arrest
148
These cardiac dysrhythmias with succinylcholine dosing are due to?
- Succinycholine actions at cardiac muscarinic cholinergic receptors where succinylcholine mimics acetylcholine effects.
* most likely to occur when a second dose follows 5 minutes after first dose*
149
Will atropine prevent second dose bradycardia in succinylcholine?
no;but pretreatment with a non-depolarizing muscle relaxant may.
150
IV succinylcholine in children may result in deadly arrhythmias due to(2)?
When this occurs, what should be suspected?
- rhabdomyolysis & hyperkalemia
| - underlying myopathy
151
If a healthy appearing kid develops cardiac arrest after succinylcholine not due to inadequate ventilation, oxygenation or anesthesia OD, what 4 IMMEDIATE treatments for hyperkalemia should be instituted?
*****Quiz Question*****
1. IV calcium
2. bicarbonate
3. glucose with insulin
4. hyperventilation
152
It is recommended that the use of succinylcholine in children be reserved for(5)?
- emergency intubation
- laryngospasm
- difficult airway
- full stomach
- IM use when a suitable vein is inaccessible
153
What 2 conditions may occur related to the head/eyes immediately after injection of Succ and during fasciculation's?
- increase in intraocular pressure
| - increase in ICP
154
Succ maximally increases IOP how many minutes post administration? This IOP last only how long?
2-4 minutes
| 5-10 minutes
155
The mechanism of action for IOP with such administration is due to(2)?
- contraction of extra-ocular muscles
- Succinylcholine cycloplegic actions with deepened anterior chamber and increased resistance to aqueous humor flow
*SUCCINYLCHOLINE SHOULD BE AVOIDED WITH OPEN GLOBE INJURES*
156
Succinylcholine produces inconsistent increases in intragastric pressures related to?
fasciculations
*Pretreatment with non-depolarizers prevents increases in intragastric pressures*
Children do not have intragastric pressures > 20 cm H2O even without pre-treatment
157
TOF = No response
What % blockade
What clinical significance?
100% blocked; suitable for intubation
158
TOF = one twitch(response)
What % blockade
What clinical significance?
90% blocked; suitable for ventilation
159
TOF = two twitches(responses)
What % blockade
What clinical significance?
80-90% blocked; suitable for short term relaxation
160
TOF = three twitches(responses)
What % blockade
What clinical significance?
75-80% blocked; maintenance doses needed
161
TOF = four twitches(responses)
What % blockade
What clinical significance?
0-75% blocked; rapid cholinesterase inhibitors reversal
