Nondepolarizing NMBD Reversal Agents Flashcards
1
Q
What is the Enzyme responsible for rapid acetylcholine hydrolysis?
A
Acetylcholinesterase
2
Q
How many molecules of acetylcholine are hydrolyzed per second?
A
Very efficient-4,000 molecules
3
Q
Where is Acetylcholinesterase highly concentrated?
A
within the neuromuscular junction
4
Q
What is another name for Anticholinesterases?
A
Acetylcholinesterase Inhibitors
5
Q
What is the mechanism of action of Anticholinesterases?
A
Inhibition of acetylcholinesterase increases the amount of acetylcholine in the neuromuscular junction
6
Q
Anticholinesterases: What effect does Increased acetylcholine have?
A
competes with residual neuromuscular blocking drug molecules for a binding site on the nicotinic receptors
7
Q
What causes the side effects of Anticholinesterases?
A
Concomitant increase of acetylcholine at muscarinic receptors (results in the side effects)
8
Q
What are some examples of Acetylcholinesterase inhibitors? (3)
A
neostigmine, edrophonium, pyridostigmine
9
Q
Why are Acetylcholinesterase inhibitors used clinically?
A
to antagonize the residual effects of neuromuscular blockers and to accelerate recovery from nondepolarizing neuromuscular blockade
10
Q
What effects recovery of muscle relaxation?
A
induced by nondepolarizing neuromuscular blockers ultimately depends on the elimination of the neuromuscular blocker from the body
11
Q
What should dosing anticholinesterases be based on?
A
DEPTH OF BLOCK
12
Q
How is depth of block determined?
A
MONITORING NEUROMUSCULAR EVOKED RESPONSES: TRAIN OF FOUR (TOF)
13
Q
What is an objective monitoring system for nerve block?
A
acceleromyography (gold standard)
14
Q
What is another example of block depth monitoring?
A
measured TOF ratio number (0.1-1.0)
15
Q
What is subjective block monitoring?
A
Subjective monitoring: visual/tactile evoked responses observed to stimulation of a peripheral nerve using a peripheral nerve stimulator
16
Q
Objective ________, use subjective if not available
A
preferred
17
Q
What is the train of four count for intense (profound) block and deep block?
A
0
18
Q
What is the train of four count for moderate block?
A
1-3
19
Q
What is the train of four count for light (shallow), minimal (near recover) and full recover (normal function) block?
A
4
20
Q
What is the measured train of four count (objective) for moderate, intense (profound) block and deep block?
A
0
21
Q
What is the measured train of four count (objective) for light (shallow) block?
A
0.1-0.4
22
Q
What is the measured train of four count (objective) for minimal (near recovery) block?
A
> 0.4 and <0.9
23
Q
What is the measured train of four count (objective) for full recovery (normal function) block?
A
> 0.9-1.0
24
Q
What is the only measured train of four reading where reversal is not needed?
A
> 0.9-1.0
25
What is the most common acetylcholinesterase inhibitor?
Neostigmine (Prostigmine)
26
What does Neostigmine (Prostigmine) also inhibit?
inhibits plasma cholinesterase
27
What is the IV dose of Neostigmine (Prostigmine) for moderate neuromuscular blockade (TOF >2)?
0.05-0.07 mg/kg for antagonism of moderate neuromuscular block
28
What is the IV dose of Neostigmine (Prostigmine) for light-minimal neuromuscular blockade (TOF of 4 with tactile or visual fade)?
0.02-0.03 mg/kg
29
What is the maximum dose of Neostigmine (Prostigmine)?
5 mg
30
What is the onset of Neostigmine (Prostigmine)?
Slower acting (7-11 minutes)
31
What is Neostigmine (Prostigmine) usually paired with? Why?
with glycopyrrolate (7-15 ug/kg) due to onset timing (attenuate muscarinic side effects)
32
Why is additional doses of neostigmine not recommended?
Administering additional doses of neostigmine are not recommended because the concentration of acetylcholine that can be produced at the neuromuscular junction is finite
33
What can the anticholinesterases not antagonize?
Because of this ceiling effect, the anticholinesterases CANNOT effectively antagonize profound or deep levels of neuromuscular blockade
34
Moderate nondepolarizing blockade with a TOF ________ should not be reversed with neostigmine
below 2
35
What can happen with a neostigmine dose of >5mg?
may actually prolong degree of blockade
36
What is the drug class of Edrophonium (Enlon, Tensilon)?
Acetylcholinesterase inhibitor
37
When was Edrophonium (Enlon, Tensilon) discontinued?
Discontinued in 2018
38
What is the onset of Edrophonium (Enlon, Tensilon)?
Rapid acting, faster onset than neostigmine (1-2 minutes)
39
What is the potency of Edrophonium (Enlon, Tensilon)?
1/12 the potency of neostigmine
40
What is the dose of Edrophonium (Enlon, Tensilon)?
1-1.5 mg/kg
41
What is Edrophonium (Enlon, Tensilon) usually paired with?
atropine (7-10 ug/kg) due to onset
42
What is Enlon Plus?
edrophonium plus atropine mixed
43
What is the elimination half-life of Edrophonium (Enlon, Tensilon)?
Elimination half life of edrophonium is similar to neostigmine (approximately 50-100 minutes)
44
What is the excretion of Edrophonium & Neostigmine?
Renal excretion accounts for about 50% of the excretion of neostigmine and 75% of edrophonium
45
What effect is seen with renal failure for those given Edrophonium & Neostigmine?
Renal failure decreases the plasma clearance of neostigmine and edrophonium
46
What does inhibition of acetylcholinesterase do?
increases the concentration of acetylcholine at the neuromuscular junction (nicotinic site) and to all other synapses that acetylcholine acts as a transmitter (muscarinic)
47
What are the cardiovascular muscarinic effects of anticholinesterases? Why is this caused?
Bradycardia due to activation of the muscarinic and nicotinic acetylcholine receptors in the parasympathetic nervous system
48
What are the two most common anticholinesterases?
Edrophonium & Neostigmine
49
What can be administer to minimize the cardiovascular muscarinic effects of anticholinesterases?
Administer an anticholinergic agent to minimize muscarinic CV side effects
50
What are the pulmonary muscarinic effects of anticholinesterases? (5)
Bronchoconstriction, bronchospasm, Increased airway resistance, increased salivation, and increased bowel (attenuated by administering an anticholinergic)
51
What is a caveat to administration of Anticholinesterases?
Unnecessary (too much) administration of anticholinesterase can cause muscle weakness
52
What is the MOA of muscle weakness from too much) administration of anticholinesterase ?
Weakness of the airway dilator muscle genioglossus can lead to upper airway collapse during inspiration
53
Unnecessary administration of neostigmine can also cause ____________
diaphragmatic dysfunction
54
Reversal Guide: What is the neostigimine dose for posttentanic count <2?
Delay reversal
55
Reversal Guide: What is the Sugammadex dose for posttentanic count <2?
4-16 mg/kg
56
Reversal Guide: What is the Sugammadex dose for posttentanic count >2?
2-4 mg/kg
57
Reversal Guide: What is the neostigimine dose for posttentanic count >2?
Delay reversal
58
Reversal Guide: What is the neostigimine dose for TOF count of 2-4?
0.05-0.07 mg/kg
59
Reversal Guide: What is the Sugammadex dose for TOF count of 2-4?
1-2 mg/kg
60
Reversal Guide: What is the neostigimine dose for TOF count of 4, no tactile or visual fade?
0.02-0.03 mg/kg
61
Reversal Guide: What is the Sugammadex dose for TOF count of 4, no tactile or visual fade?
0.25-0.5 mg/kg
62
What is the drug class of Sugammadex (Bridion)?
New drug class: selective relaxant-binding agent
63
What is the MOA of Sugammadex (Bridion)?
Sugammadex compound encapsulates steroidal neuromuscular blocking drugs (especially rocuronium)
64
What is the potency of Sugammadex for certain NMBD?
Rocuronium > vecuronium >> pancuronium
65
What degree of neuromuscular block can Sugammadex reverse?
Reversal can be accomplished even with a profound neuromuscular block
66
What doesn't need to be administered with Sugammadex?
No need for administration of anticholinergic drugs
67
What effect does Sugammadex have on acetycholinesterase?
Has no effect on acetycholinesterase
68
What is the structure of Sugammadex?
Cyclodextrin molecule with a hydrophilic exterior and lipophilic center allowing encapsulation of aminosteroid blocking agents, greatest affinity for rocuronium
69
How long does it take for Sugammadex to reverse NMBD?
Capable of reversing shallow to profound neuromuscular blockade induced by rocuronium or vecuronium within 3 minutes
70
What is the movement of NMBD molecules from the plasma by Sugammadex?
- Rapid removal of free rocuronium or vecuronium molecules from the plasma
- This creates a concentration gradient favoring movement of the remaining rocuronium or vecuronium molecules from the NMJ back into the plasma, where they are encapsulated by free sugammadex molecules
71
What does Sugammadex do within the tissues?
Sugammadex molucules also enter tissues and form a complex with the rocuronium or vecuronium
72
Sugammadex: Neuromuscular blockade of these agents is terminated rapidly by their diffusion ___________
away from the NMJ back into the plasma
73
What is the age range for safe drug administration of Sugammadex?
Approved (finally in 2015) for use in adults and children ages 2-17
74
What is the plasma proteins of Sugammadex?
Sugammadex is biologically inactive, does not bind to plasma proteins
75
What is the kinetics of Sugammadex?
Kinetics are dose dependent – as clearance increases, elimination half life decreases
76
What is the characteristics of the sugammadex-rocuronium complex?
Because of the soluble nature of the sugammadex-rocuronium complex, urinary excretion of the complex is the major route of elimination of the rocuronium (65-97% of the administered dose is recovered in urine)
77
What is the metabolism of sugammadex?
Metabolism of sugammadex is very limited - the drug is predominately eliminated unchanged by the kidneys
78
What effect does kidney impairment have on clearance of sugammadex?
With substantial renal impairment, clearances of sugammadex and sugammadex-drug complex are decreased
79
Who should sugammadex be avoided in?
Avoid sugammadex in patients with a creatinine clearance of < 30 mL per minute
80
What is sugammadex removable by?
dialysis
81
What is the recommended sugammadex dose for rocuronium or vecuronium (per fda) if the twitch response has reached 1-2 post tetanic counts and there are no twitch responses to train-of-four (TOF) stimulation?
4 mg/kg is recommended
82
What is the recommended sugammadex dose for rocuronium or vecuronium (per fda) if spontaneous recovery has reached the reappearance of the second twitch in response to TOF stimulation?
2 mg/kg is recommended
83
What is the recommended sugammadex dose for rocuronium if if there is a clinical need to reverse neuromuscular blockade soon (approximately 3 minutes) after administration of a single dose of 1.2 mg/kg of rocuronium?
16 mg/kg is recommended
84
What is sugammadex ineffective against reversing?
Sugammadex is ineffective against succinylcholine and benzoisoquinolinium neuromuscular blockers (mivacurium, atracurium, cisatracurium)
85
What can sugammadex cause in high doses?
bradycardia
86
What is an important teaching requirement for sugammadex for women on birth control?
- May decrease effectiveness of progesterone up to 7 days!
| - Usually sent home with a letter to advise
87
What is the MOA of anticholinergic drug?
Produce their effects by competitively and reversibly binding to muscarinic cholinergic receptors at PNS neuroeffector sites on smooth muscle, cardiac muscle and gland cells, at other muscarinic receptors in the CNS, and on preganglionic fibers in the peripheral autonomic ganglia
88
What is the cardiac muscarinic receptors?
M2
89
What is the pulmonary/airway smooth muscle muscarinic receptors?
M2 & M3
90
What is other name for M1 receptors?
Neural
91
What is other name for M3 receptors?
Glandular muscarinic receptors
92
What is the location of M1 receptors?
Exocrine glands & autonomic ganglia
93
What is the affects of M1 receptors?
Arousal, attention, REM, emotional response, affective disorder
94
What is the location of M2 receptors?
Atria and conducting tissue of the heart
95
What is the affects of M2 receptors?
Cardiac inhibition
96
What is the location of M3 receptors?
Exocrine glands and smooth muscle
97
What is the affects of M3 receptors?
Lacrimal, salivary, mostly stimulatory effect
98
What is the affects of M4 receptors?
CNS
99
What is the affects of M4 receptors?
direct regulatory action on K and Ca ion channels
100
What is the location of M5 receptors?
substantia nigra (cns)
101
What is the affects of M5 receptors?
may regulate dopamine release at terminals with the striatum
102
Describe the muscarinic receptor activation in airway smooth muscle.
The pulmonary neuronal M2 muscarinic receptor. Acetylcholine released from pulmonary vagal nerves stimulates muscarinic M3 receptors on airway smooth muscle causing smooth muscle contraction; at the same time acetylcholine stimulates M2 muscarinic receptors located on the postganglionic nerves. Stimulation of these neuronal M2 muscarinic receptors limits further acetylcholine release.
103
What are the indications for Utilization of Anticholinergic Agents Perioperatively?
- Prevent bradycardia when an anticholinesterase agent is administered
- Treat bradycardia
- PONV prophylaxis/motion induced nausea
- Sedation
- Antisialagogue
- Bronchodilator
104
What anticholinergic agent can be used to prevent bradycardia when an anticholinesterase agent is administered? (2)
glycopyrrolate & atropine
105
What anticholinergic agent can be used to treat bradycardia? (2)
glycopyrrolate & atropine
106
What anticholinergic agent can be used to PONV prophylaxis/motion induced nausea?
scopolamine
107
What anticholinergic agent can be used for Sedation?
scopolamine
108
What anticholinergic agent can be used for Antisialagogue? (3)
glycopyrrolate, atropine, scopolamine
109
What anticholinergic agent can be used for bronchodilation? (2)
ipratropium/Atrovent
110
What is the MOA of atropine?
Competitive antagonist of ACh at muscarinic M2 receptor
111
What is the history of atropine?
Belladonna alkaloid (from the deadly nightshade plant): woman would take to make pupils larger (more aesthetic at the time)
112
What is the permeability of atropine across the BBB? Why? What does is this not really an issue?
Tertiary amine so will cross the blood-brain barrier (usually not an issue with therapeutic doses of 0.2-0.4 mg)
113
Who should atropine be used in cautiously in?
- Caution with elderly (central effects)
| - Caution with children as can block ACh sympathetic sweat glands
114
What are the anesthetic uses of atropine?
Anesthetic uses: treat bradycardia (vagolytic), treat excessive secretions (antisialogogue)
115
What can lower doses of atropine cause?
Lower doses may result in paraydoxical bradycardia: central vagotonic effect on SA node (< 0.5 mg)
116
Why should atropine be used cautiously in patients with angle-closure glaucoma?
will raise intraocular pressure
117
What is the onset of atropine?
1-2 minutes
118
What is the metabolism of atropine?
50% hepatic metabolism
119
What is central anticholinergic syndrome?
”atropine poisoning” ,“atropine fever” – too much atropine, tx with physostigmine (anticholinesterase drug)
120
What is the atropine dose of adults for IV/IM?
0.5-1 mg
121
What is the IV pediatric dose of atropine?
0.02 mg/kg
122
What is the IM pediatric dose of atropine?
0.02-0.04 mg/kg
123
What is the structure of glycopyrrolate? How does this effect the permeability?
Quaternary ammonium that does NOT cross blood brain barrier
124
What does not occur with Glycopyrrolate?
does not contribute to postop delirium that can occur with atropine or scopolamine
125
Glycopyrrolate: Less _______ than atropine
Tachycardia
126
What is the ionization of Glycopyrrolate?
Highly ionized with Vd of 0.42 L/kg.
127
What is the onset of Glycopyrrolate?
1 minute
128
How long do antisialagogue effects of Glycopyrrolate last?
effects lasting up to 7 hours, duration of up to 4 hours
129
What is the elimination of Glycopyrrolate?
over 80% unchanged in the urine
130
How can Glycopyrrolate & atropine effect the esopheageal sphincter?
Both atropine and glycopyrrolate can transiently decrease lower esophageal sphincter (LES) tone (concern with reflux)
131
What is the reversal dose of Glycopyrrolate for adults?
0.01-0.02 mg/kg when co-administered with neostigmine (usually close to 1:1 [ml] with neostigmine)
132
What is the dose of Glycopyrrolate for bradycardia and antisialogogue?
0.1-0.4 mg
133
What is the dose of Glycopyrrolate in pediatrics?
0.01 mg/kg
134
What is the structure of Scopolamine?
Tertiary amine – crosses the blood-brain barrier
135
What is a common side effect of Scopolamine?
drowsiness
136
What are the indications for Scopolamine (3)?
- PONV prophylaxis
- Anterograde amnesia
- Sedation
137
What are the precautions Scopolamine?
Patients with cognitive dysfunction – can attenuate CNS effects with co-administration of a benzo
138
What other effects does Scopolamine have (2)?
Inhibits bowel and bladder tone
139
Who should Scopolamine be avoided in?
in patients with intestinal obstruction & urinary obstruction
140
What is the adult IV dose of Scopolamine?
0.3-0.65 mg over 2 minutes
141
What is the pediatric dose of Scopolamine for 6months-3 years old?
0.1-0.15 mg
142
What is the pediatric dose of Scopolamine for 3 years-6 years old?
0.2-0.3 mg
143
What is the transdermal dose of the patch of Scopolamine?
1.5 mg (over 3 days)
144
What are the clinical manifestations of anticholinergic toxicity? (6)
```
Dry mouth
Tachycardia
Fever
Impaired vision
Cutaneous flushing
CNS manifestations
```
145
What are the CNS manifestations of anticholinergic toxicity? (6)
- Restlessness, irritability, hallucinations, unconsciousness
- Delayed awakening from anesthesia, ventilatory depression
146
What is the treatment for anticholinergic toxicity?
Physostigmine 15-60 mcg/kg, may need to be repeated in 15-30 minutes
147
What drug class is Physostigmine?
Cholinesterase inhibitor
148
What is the structure of Physostigmine? What impact does it have on its permability of the BBB?
Lipid soluble tertiary amine, crosses the blood-brain-barrier
149
What is the MOA of Physostigmine?
Counteracts symptoms by increasing the amount of acetylcholine available to compete for muscarinic receptor binding
