PPT neuromuscular blocking and reversal Flashcards
1
Q
First successful administration of NMB?
A
Curare in 1912 by Arthur Lawen a German Surgeon.
2
Q
What type of antagonist is a nondepolorizing NMB?
A
competative antagonist.
3
Q
Tell me how Succ works?
A
Succ. produces a prolonged depolarization of the endplate region that results in desensitization of nicotinic acetylcholine receptors; inactivation of voltage gated sodium channels at the neuromuscular junction and increase in potassium permeability in the surrounding membrane. Thus producing the failure of the action potential generation due to membrane hyperpolarization and a block ensues
4
Q
what is responsible for the rapid hydorlysis of released acetylcholine to acetic acid and choline?
A
acetylcholinesterase (true cholinesterase)
5
Q
what hydrolysis succ, and where does it occur?
A
plasma cholinesterase or pseudocholinesterase and it occurs mainly in the plasma.
6
Q
what are all neuromuscular blockers structurally related to?
A
acetylcholine
7
Q
what is the one NMB that is not a synthetic alkaloid?
A
tubocurarine which is extracted from the Amazonian vine (cheaper this way)
8
Q
Nondepolorizing NMB what twho classes are their?
A
Steroidal
Benzylisoquinoinium
9
Q
example of a Benzylisoquinolinium?
A
South American Indian’s arrow poisons. Tubocurarine is the most important curare alkaloid.
Atracurium
cisatracurium (nimbex)
10
Q
what type of patients should you not use tubocurarine with?
A
not suitable for renal or liver failure patients.
11
Q
intubating dose of tubocurarine?
A
.5-.6mg/kg
12
Q
Atracurium (what is important about it’s metabolism?)
A
can undergo ester hydrolysis
13
Q
what does laudanoisine depend on?
A
depends on the liver for clearance with ~70% excreted in bile with remainder in the urine
14
Q
what is laudanoisine?
A
a metabolite of the neuromuscular-blocking drugs atracurium and cisatracurium with potentially toxic systemic effects. It crosses the blood-brain barrier easily and may cause excitement and seizure activity
15
Q
what patients would laudanoisine be a problem with?
A
not good for liver patients, liver cirrhosis (according to class notes from Hammon talking)
16
Q
cisatracurium tell me about it?
what does it come from, what elimination does it use, histamine? What patients would you use it with?
A
Isomer of atracurium
hoffman elimination to laudanosine and monoquatenary alcohol metabolie.
Hoffman is 77% of clearance
does not cause histamine release like atracturium if given in clinical dose range.
Good for patients with renal issues.
17
Q
where does hoffman elimination occur?
A
in the plasma?
18
Q
list steroidal NMB?
A
Pancuronium
Vecuronium
Rocuronium
19
Q
Pancuronium remains stable for how long at room temp?
A
6 months
20
Q
Vecuronium, if you have what kind of issues this med will last longer on you?
A
liver issues (principal elimination is liver)
21
Q
which will you have to re-dose more often Vec or Roc?
A
Vecuronium
22
Q
Rocuronium, onset time and potency?
A
fast onset (1-3 min depending on dose) 6 times less potent than vecuronium.
23
Q
Roc is stable at room temp for how long?
A
60 days
24
Q
in relation to NMB ED50 and ED95 would mean?
A
ED50 is 50% reduction in twitch height, and ED95 is 95% reduction in twitch height.
25
inhalation anesthetics potentiate the NMBlocking effects of NMB, list from most to least to potentiate.
DES>SEVO>ISO>HALO>Nitrous Oxide>barbiturate>propofol
26
Can Des affect your Rocuronium?
YES! Potentiates it.
27
Can antibiotics potentiate NMB? If so then how?
Yes, All inhibit the prejunctional release of acetylcholine and also depress postjunctional nicotinic acetylcholine receptor sensitivity to acetylcholine
28
Whats the relationship between clindamycin, penicillin and Ancef?
Clindamycin was given to people with allergy to penicillin at one time, so that is why you will see it, otherwise they take ancef.
Link thought between penicillin and ancef, but has now been found false.
29
what antibiotics potentiate NMB?
```
aminoglycosides
polymyxins
lincomycine
clindamycin
and tetracycline (exhibits post junctional activity only)
```
30
name some other conditions or drugs that potentiate blockade of NMBD?
hypothermia
magnesium sulfate
High magnesium concentrations inhibit calcium channels at the presynaptic nerve terminals that trigger the release of acetylcholine
quinidine an antidyshythmic
31
What drugs or conditions will decrease the potency of NMBD?
Chronic use of anticonvulsant therapy
hyperparathyroidism, hypercalcemia is associated with decreased sensitivity to atracurium and thus a short duration of neuromuscular blockade.
32
what will eat up your drugs quicker?
anticonvulsant therapy and street drug usage.
33
link between potency and onset of action of NMBD?
Onset of action is inversely proportional to potency of NMBD
Low potency = rapid onset
High potency = slow onset
34
What NMBD is the exception to the potency and drug onset time inverse rule?
atracurium
35
what is potency expressed in and why?
moles per kilogram
ultimately, we have a variable number of molecules chasing a fixed number of nicotinic receptors. The fewer molecules it takes (per kilogram of body weight) to achieve a given degree of receptor occupancy, the greater the affinity the drug has for the receptor. This is best expressed in micromoles per kilogram rather than in milligrams per kilogram.
36
what is buffered diffusion and what drugs does it occur with?
The process in which diffusion of a drug is impeded because it binds to extremely high-density receptors within a restricted space
Can be seen with high potency but not low potency drugs
Buffered diffusion causes repetitive binding to and unbinding from receptors keeping potent drugs such as tubocurarine in the neighborhood of effector sites and potentially lengthening the duration of effect
37
Explain the autonomic effects of NMBD?
NMBD interacts with nicotinic and muscarinic cholinergic receptors within the SNS and PNS and at the nicotinic receptors of the neuromuscular junction.
38
Adverse effects of tubocurarine?
marked ganglion blockade resulting in hypotension;
histamine manifestations (hypotensin, reflex tachy,bronchospasm) in susceptible patients.
39
adverse effects of pancuronium?
direct vagolytic effect. Can block muscarinic receptors on sympathetic postganglionic nerve terminals resulting in inhibition of a negative feedback mechanism whereby excessive catecholamine release is modulated or prevented Can also stimulate catecholamine release from adrenergic nerve terminals.
40
Benzylisoquinoliniums release histamine what can occur bc of this and which NMBD that falls under this category does not release histamine?
How can you help prevent histamine release?
the exception is cisatracurium.
release histamine can cause increase airway resistance and bronchospasm in patients with hyperactive airway disease
also, skin flushing, hypotension, decreased SVR, increased pulse rate.
slow administration over 60 sec.
prophylactic use of combined histamine H1 and H2 receptor antagonists.
41
In typical doses are steroidal NMBD associated with histamine release?
NO
42
which type of reaction is mediated through immune responses involving immunoglobulin E antibodies fixed to mast cells?
anaphylactic
43
not immune mediated and represent exaggerated pharmacologic responses in very sensitive individuals who represent a very small portion of the population
anaphylactoid reaction
44
Treatment of analyphylaxis?
Turn the gas off and 100% 02
IV epi 10-20 micrograms/kg (subq if no IV)
TELL THE SURGEON bc he needs to close and you are going to wake up the patient.
If IV blows before succ is given then you gas em and get an IV.
consider intubation if angioedema develops
If you give them a pressor and it stops working (push) then give fluids they may need the circulation (give norepinephrine or a phenylephrine)
treat dysrhythmias
45
Succinylcholine what is adequate dose and what do we actually use?
0.3-0.5 mg/kg is adequate, 1.0-1.5 is commonly used.
46
half life of succ?
| what order kinetics does it follow?
47 sec.
| first order kinetics
47
side effects of Succ?
why does it have these side effects?
when are these side effects most likely to occur?
How do you prevent/treat this side effect?
Sinus brady, junctional rhythm and sinus arrest may follow administration of Sch.
This reflects actions of Sch at cardiac muscarinic cholinergic receptors where it mimics the physiologic effects of acetylcholine
Most likely to occur when two doses are given with in 5 minutes
Atropine is effective in treating and preventing bradycardia.
48
can succ. cause increased HR and increased BP?
YES! reflects succs effect on the autonomic ganglia (acting like acetylcholine)
49
administration of succs during laryngoscopy and tracheal intubation have sometimes resulted in what?
Ventricular dysrhythmias
50
Succs can cause a transient increase in what?
Do to this what patients should not have succs?
transient increased in plasma potassium of 0.5mEq/L (well tolerated in normal patients)
```
Patients with renal failure are more susceptible to exaggerated potassium increases. caution should be taken in the following patients: renal failure
metabolic acidosis
closed head injury
burns
hemiplegia or paraplegia
muscular dystrophies, GB
abdominal infections.
```
51
Is succs used routinely in children?
succs use in children should be for emergency tracheal intubation only bc of the risk of undiagnosed muscle disease leading to death with use in children under the age of 12.
52
myoglobinuria and rhabdo caused in patients due to succs means what?
they have MH or muscular dystrophy
53
Why is succs. not widely accepted in open eye cases?
can cause increased IOP with peak in 2-4 min and duration of 6 min.
54
is regurgitation a problem with succs. use?
NO, does not predispose people to regurgitation.
55
Myalgia and succs?
muscle pain can happen due to succs. use. even with defasciculation dose of non depolarizers.
56
Masseter spasm and succs, tell me about it?
Sch is a trigger for MH, if this was to occur then you may have masseter spasm. OTHER possibilities is you did not give enough succs or you need to let it work longer, these two scenarios should trump the forethought of MH. Masseter spasm would be the earliest sign of MH but not the most sensitive sign.
57
ABSENCE OF FADE AND TETANIC TO TOF describes which kind of NMB?
Depolarizing NMB = Succs. (phase I)
58
what is phase II in relation to succs?
PHASE II BLOCKADE IS PRESENT WHEN THE POST JUNCTIONAL MEMBRANE HAS BECOME REPOLARIZED BUT STILL DOES NOT RESPOND NORMALLY TO ACh (DESENSITIZATION NEUROMUSCULAR BLOCKADE)
59
phase II, how does it act on TOF?
Fade is seen in response to TOF when in phase II (bc in phase one their is no fade seen, just the same all the way across)
60
What is responsible for the fasciculations seen with succs?
SUSTAINED DEPOLARIZATION PRODUCED BY THE INITIAL ADMINISTRATION OF SCh IS INITIALLY MANIFESTED AS TRANSIENT GENERALIZED SKELETAL MUSCLE CONTRACTIONS
61
What mechanism from succs. is responsible for the increased potassium?
SUSTAINED OPENING OF SODIUM CHANNELS PRODUCED BY SCh IS ASSOCIATED WITH LEAKAGE OF POTASSIUM FROM THE INTERIOR OF CELLS
62
is plasma cholinesterase present in the NMJ?
NO, plasma cholinesterase rapidly hydrolyzes and decreases the amount of SCh in the extracellular fluid before reaching the NMJ.
63
SCh should NOT be given to patients 24-72 hours after? and why?
major burns
trauma
extensive denervation of skeletal muscles.
may result in acute high potassium and cardiac arrest.
64
what happens if you give a 2nd dose of SCh within five min of the first dose?
cardiac dysrhythmias are most likely to occur (bradycardia then asystole)
65
what would you give to decease the likelihood of a cardiac response to sux?
atropine 1-3 min before sux.
66
Does atropine IM reliably protect against sux induced bradycardias?
NO IM atropine does not.
67
if you have given a NMB and your patient has four twitches what can that mean?
75% or less receptors are blocked, thus it means 75% of receptors could be blocked and you see four twitches.
68
If you see 0 twitches on TOF after giving a NMB what would that mean?
100% receptors are blocked.
69
Twitches on the TOF with correlating amount of receptors that could be blocked, tell me all of em?
4 = NO DRUGS
4 = WITH DRUG = 75% OR LESS RECEPTORS BLOCKED
3 = WITH DRUG = 85% OR LESS RECEPTORS BLOCKED
2 = WITH DRUG = 95% OR LESS RECEPTORS BLOCKED
1 = WITH DRUG = 99% OR LESS RECEPTORS BLOCKED
0 = WITH DRUG = 100% RECEPTORS BLOCKED
70
what enzyme is highly concentrated at the NMJ?
acetylcholinesterase
71
Acetylcholinesterase is fast, just how fast is it?
it can hydrolyze nearly as fast as the rate of diffusion!
72
In the NMJ what kind of receptors is Ach trying to reach?
nicotinic acetylcholine receptors.
73
What are the three acetylcholinesterase inhibitors?
Neostigmine (common)
Edrophonium
Phridostigmine (less common)
74
How do acetylcholinesterase inhibitors work?
The acetylcholine that accumulates at the neuromuscular junction after administration of neostigmine competes with the residual molecules of neuromuscular blocking drug for the available unoccupied nicotinic acetylcholine receptors at the neuromuscular junction.
75
once the inhibition of Achesterase is complete does administering additional doses of neostigmine serve any purpose?
NO
76
How do you know if neostigmine has done it's job?
when you get a 4th response on TOF
77
When will you leave your patient tubed after NMB?
if LESS than 4 twitches
78
what should you have before you even give neostigmine?
at least one twitch
79
what will you give neostigmine with and what are the mg of each?
glycopyrrolate 5mg first then neostigmine 4mg to follow.
80
Neostigmine, what is the MAX effective dose range?
60-80mcg/kg
81
Edrophonium what is its range dose?
1.0-1.5mg/kg range
82
of the three NMBD reversals (acetylcholinesterase inhibitors) which has the longest half life?
pyridostigmine
83
Renal excretion is 50% or more for the three NMBD reversals, what does this mean?
Renal failure decreases the plasma clearance of all three as much as or more than that of the longer acting NMBD
84
why is glyco co-administered with acetylcholinesterase inhibitors and anticholinergics?
to minimize the muscarinic cardiovascular side effects. BC by inhibiting the break down of Ach you increase Ach in all synapses all over the body not just at the NMJ.
85
Acetylcholinesterase inhibitor and anticholinergics should be given at what push rate?
slowly over 2-5 min.
86
tell me which Acetylcholinesterase inhibitors and anticholinergics are co-adminstered?
Atropine 7-10 mcg/kg and edrophonium 0.5 – 1.0 mg/kg both are rapid
Glycopyrrolate 7-15 mcg/kg and neostigmine 40-70 mcg/kg both are slower
Glycopyrrolate also pairs with pyridostigmine
87
long acting steroidal NMB? (greater than 50 min)
PANCURONIUM (the other two are intermediate (vec and roc))
88
Benzylispquinolinium long intermediate and short acting NMB.
long= tubocurarine
intermediate = atracurium and cisatracurium
short = mivacurium
89
if someone has a pre-existing cardiac dz which anticholinergic is desired? WHY?
glycopyrrolate over atropine.
Atropine tends to overshoot on the increase in HR which creates myocardial demand for 02 and possibility of heart attack.
90
list the side effects of anticholinergic's? (atropine, glyco, scopalamine)
```
hot as a hare
dry as a bone
blind as a bat
red as a beat
mad as a hatter
```
91
cholinergic mnemonic?
```
SLUDGEM
saliva
lacrimation
urination
diarrhea
GI cramping
emesis
Miosis/muscle twitching
```
92
what should be the milligram max of neostigmine and what should be the mcg max?
40-70 or 60-70mcg/kg
5MG SHOULD BE THE MAX!
93
Whats a good dose of glycopyrolate according to the ppt?
7-15mcg/kg is a good dose
94
what two drugs prevent the cardiac muscarnic effects (bradycardia)?
atropine or glycopyrrolate. (robinul most commonly used)
95
Highly water soluble with a hydrophobic cavity large enough to encapsulate steroidal neuromuscular blocking drugs?
SUGAMMADEX
96
What NMB does sugammadex work on?
Rocuronium > Vecuronium >> Pancuronium (steroidal)
97
Will sugammadex work on Nimbex, Atrocurium, or Tobac?
NO
98
what is so great about sugammadex and with which NMB does it work the best?
works the best with Rocuromium.
Has a very high associate rate and very low dissociate rate with rocuronium. Estimated for every 30 million Sugammadex-Rocuronium complexes, only one complex will disassociate.
Reversal can be accomplished even during profound neuromuscular block because of its encapsulation method.
99
Does sugammadex bind to plasma proteins?
No
100
how is sugammadex, sugammadex-rocuronium complex eliminated?
urinary elimination is the major route.
101
Rocuronium is eliminated primarily by?
biliary excretion (75%) and renal (10-25%)
102
who would clearance of sugammadex-Roc complex be decreased in?
Patients with substantial renal impairment.
103
who should avoid sugammadex?
patients with a creatinine clearance less than 30ml/min
104
if you have already given sugammadex and want to cause NMBlockade what would you use?
NMBD that is under the cat. benzylisoquinolinium bc Sugammadex does not work on those!
105
can you use sugammadex if no twitches?
yes, max dose for profound block is 8-16mg/kg
106
whats another name for Sugammadex?
BRIDION
107
Which two steroidal NMB drugs will you use Bridion for?
Roc and Vec only (not pancuronium)
108
Bridion can reverse profound block in how long?
2-3 min.
109
Sugammadex- does it have any cardiovascular effects and what weight do we give it based on?
No cardiovascular effects and you give it based on actual body weight.
110
Bridion (sugammadex) and birth control?
use a different non hormonal version of birth control if you have had Bridion. Hormonal contraceptives are less effective after being given Bridion. use this other form of birth control for at least 7 days.
111
dose of Sugammadex based on 2 twitches or 1-2 twitches?
2mg/kg for 2 twitches
4mgkg for 1-2 twitches
