Nondepolarizing NMBDs Flashcards
1
Q
What is the action of Nondepolarizing NMBDs?
A
act as competitive antagonists by binding to the α subunits of the nAChR
2
Q
What do the Nondepolarizing NMBDs bind to?
A
to one of the α subunits
3
Q
What does Nondepolarizing NMBDs binding cause?
A
doesn’t open channel, blocks depolarization
4
Q
What are the classifications of Nondepolarizing NMBDs?
A
Chemical class & Duration of action
5
Q
What are the different chemical class of Nondepolarizing NMBDs?
A
steroidal, benzylisoquinolinium
6
Q
In general, dose of ________ ED95 is used to facilitate tracheal intubation and dose of ______ of the ED95 is used to maintain neuromuscular blockade
A
2-3x; 10%
7
Q
What substance was the basis for development of the benzylisoquinolinium-type muscle relaxants? What historical impact did it have?
A
Curare (South American Indians’ arrow poisons)
8
Q
What is tubocurarine? What was its only clinical use?
A
not currently in use anymore d/t side effects,
De-fasciculating dose (priming dose) 3 mg- primary purpose when it was used
9
Q
What Benzylisoquinolinium Compounds are currently in use? (3)
A
Atracurium, Cisatracurium, Mivacuronium
10
Q
What is the structure of Atracurium (Tracrium)?
A
Racemic mixture of 10 stereoisomers
11
Q
What is the metabolism of Atracurium (Tracrium)?
A
Undergoes spontaneous degradation at physiologic temperature and pH by Hoffman elimination and can also undergo ester hydrolysis
12
Q
What does metabolism of Atracurium (Tracrium) yield (2)?
A
yielding laudanosine and a monoquaternary acrylate as metabolites
13
Q
What is laudanosine? What is its clearance?
A
is liver dependent for clearance, with 70% excreted in bile (excretion of this metabolite is impaired in patients with biliary obstruction)
14
Q
What is the permeability of Atracurium (Tracrium) to the BBB and CNS?
A
Crosses blood brain barrier and has CNS stimulating properties
15
Q
What can Atracurium (Tracrium) cause the release of?
A
histamine release
16
Q
What is a potential quality of Atracurium (Tracrium) ?
A
Neuroprotective qualities?
17
Q
What is the intubating dose of Atracurium (Tracrium)?
A
0.5 mg/kg
18
Q
What is the onset of Atracurium (Tracrium)?
A
2-4 minutes
19
Q
What is the duration of action of Atracurium (Tracrium)?
A
30-60 min. (intermediate acting)
20
Q
What is the subsequent dose of Atracurium (Tracrium)?
A
0.1-0.2 mg/kg
21
Q
What is the chemical structure of Cisatracurium (Nimbex)?
A
Cis isomer of atracurium
22
Q
What is the potency of Cisatracurium (Nimbex)?
A
4-5 times more potent than atracurium
23
Q
What is the metabolism of Cisatracurium (Nimbex)?
A
Metabolized by Hoffman elimination to laudanosine and a monoquaternary alcohol metabolite
24
Q
How much of hoffman elimination accounts for the clearance of Cisatracurium (Nimbex)?
A
Hoffman elimination accounts for 77% of the total clearance and 23% is drug is cleared through organ-dependent means (renal elimination = 16%)
25
Does Cisatracurium (Nimbex) under ester hydrolysis?
Does not undergo ester hydrolysis
26
Does Cisatracurium (Nimbex) cause histamine release?
No
27
What is the induction dose of Cisatracurium (Nimbex)?
0.1 mg/kg
28
What is the onset of Cisatracurium (Nimbex)?
2-4 minutes
29
What is the duration of action of Cisatracurium (Nimbex)?
30-60 min. (intermediate acting)
30
What is the subsequent dose of Cisatracurium (Nimbex)?
0.03 mg/kg
31
What is the only short short-acting nondepolarizing neuromuscular blocking drug available?
Mivacurium (Mivacron), (left the market in 2006, reintroduced in 2016)
32
What is the chemical structure of Mivacurium (Mivacron)?
Mix of 3 stereoisomers
33
What is the metabolism of Mivacurium (Mivacron)?
Metabolized by butyrylcholinesterase (plasma cholinesterase/pseudocholinesterase)
34
What is the rate of metabolism of Mivacurium (Mivacron)?
at about 70-88% of the rate of succinylcholine to a monoester, a dicarboxylate acid
35
What can Mivacurium (Mivacron) produced? When?
May produce histamine release, if administered rapidly
36
What is the intubation dose of Mivacurium (Mivacron)?
0.25 mg/kg given over 15 seconds
37
What is the onset of Mivacurium (Mivacron)?
2-3 minutes
38
What is the duration of action of Mivacurium (Mivacron)?
15-20 min. (short acting)
39
What is the subsequent dose of Mivacurium (Mivacron)?
0.1 mg/kg
40
What are the sterodial compounds (Aminosteroids) of NMBDs currently in practice?
Pancuronium, Vecuronium, Rocuronium
41
What is the potency of Pancuronium (Pavulon)?
Potent, long-acting
42
What properties does Pancuronium (Pavulon) have (2)?
Possesses vagolytic (increased HR) and butrylcholinesterase-inhibiting properties
43
How is Pancuronium (Pavulon) cleared? (2)
40-60% cleared by the kidneys & 11% excreted in the bile
44
How is Pancuronium (Pavulon) metabolized?
15-20% metabolized by deacetylation in the liver
45
What is true about Pancuronium (Pavulon) metabolites?
Metabolites are less potent as neuromuscular blockers and are excreted in urine
46
What important about the Pancuronium (Pavulon) accumulation?
Accumulation of the 3-OH metabolites responsible for the prolongation of the duration of the block produced by pancuronium
47
What is the intubating dose of Pancuronium (Pavulon)?
0.08 - 0.1 mg/kg
48
What is the onset of Pancuronium (Pavulon)?
2-4 minutes
49
What is the duration of action of Pancuronium (Pavulon)?
60-90 min. (long acting)
50
What is the subsequent dose of Pancuronium (Pavulon)?
0.015- 0.1 mg/kg
51
What are the characteristics of Vecuronium (Norcuron) that makes it slightly different then Pancuronium (Pavulon)?
- A slight decrease in potency
- Loss of the vagolytic properties of pancuronium
- Molecular instability in solution (explains shorter duration of action)
- Increased lipid solubility (greater biliary elimination of vecuronium than pancuronium)
52
What is the principle elimination of Vecuronium (Norcuron)?
- Liver principal organ of elimination
| - 30-40% cleared in the bile
53
Vecuronium (Norcuron): Renal excretion accounts for excretion of _______ of the administered dose
30%
54
What is the duration of action based off of for Vecuronium (Norcuron)?
Duration of action is dependent primarily on hepatic function and to a lesser extent, renal function
55
What can contribute to prolonged neuromuscular blockade from vecuronium?
During prolonged administration, the metabolite 3-OH may contribute to prolonged neuromuscular blockade
56
3-OH has ______ the neuromuscular blocking potency of vecuronium
80%
57
What is the intubating dose of Vecuronium (Norcuron)?
0.1 mg/kg
58
What is the onset of Vecuronium (Norcuron)?
2-4 minutes – you will have to bag/mask vent the patient until the onset of action
59
What is the duration of action of Vecuronium (Norcuron)?
30-60 min. (intermediate acting)
60
What is the subseqent dose of Vecuronium (Norcuron)?
0.01-0.015 mg/kg
61
What is the characteristics of Vecuronium (Norcuron) storage?
Prepared as a powder, must be reconstituted
62
What duration class is Rocuronium (Zemuron)?
Intermediate acting
63
What is the recovery of Rocuronium (Zemuron)?
Moderate recovery
64
What is the onset of Rocuronium (Zemuron)? What is its onset compared to other NMBD?
- Faster onset than pancuronium or vecuronium
| - Time to maximum block is 1.7 minutes
65
What is the potency of Rocuronium (Zemuron)?
6 times less potent than vecuronium
66
What is the primarily elimination of Rocuronium (Zemuron)? (2)
Primarily eliminated by the liver and excreted in the bile
67
Approximately _______ of rocuronium is excreted unchanged in the urine
30%
68
What is the storage of Rocuronium (Zemuron)?
At room temperature, rocuronium is stable for 60 days (is usually refridgerated)
69
What is the intubating dose of Rocuronium (Zemuron)?
0.6 mg/kg
70
What is the onset of Rocuronium (Zemuron)?
1-1.5 minutes
71
What is the RSI dose of Rocuronium (Zemuron)?
0.6-1.2 mg/kg provides good to excellent intubating conditions in 45-90 seconds
72
What is the duration of action of Rocuronium (Zemuron)?
30-60 min. (intermediate acting)
73
What is the maintenance dose of Rocuronium (Zemuron)?
0.1-0.2 mg/kg
74
What effect can two successive injections of nondepolarizing muscle relaxants have?
can decrease the onset of muscle paralysis
75
What is the priming dose?
A small sub-paralytic “priming” dose is injected about 3 minutes before the full intubating dose
76
What is the effect of the priming dose?
The priming dose, by occupying a small number of receptors, speeds the onset of effect with the subsequent dose
77
What is possible to achieve by priming?
By priming, it is possible to achieve onset times in the range of one minute
78
What can most patients show signs of following a priming dose?
As with defasciculation and SCh, some patients may show signs of weakness following the priming dose
79
Who do we need to be careful using priming doses with?
Careful with vulnerable patients- become very anxious and remember this! (“I can’t breathe”)
80
What is drug potency expressed in?
terms of the dose-response relationship
81
What is potency?
Potency is expressed as the dose of drug required to produce an effect
82
What is potency in relationship to Nondepolarizing NMBDs?
- 50% or 95% depression of twitch height (ED50 and ED95)
| - ED50 is a more robust parameter
83
What effect does inhalational anesthetics have on nondepolarizing neuromuscular blockers.
Inhalational anesthetics potentiate the neuromuscular blocking effect
84
What is required regarding the dose of nondepolarizing NMBDs with inhalational anesthetics?
Decrease in the required dosage of neuromuscular blocker and prolongation of both the duration of action of the relaxant and recovery from neuromuscular block
85
What effects the magnitude of potentiate?
is dependent upon the duration of inhalational anesthesia, the specific inhalational agent used, and the concentration of inhalational agent used
86
Rank the order of common anesthesia meds and their potentiate of non depolarizing NMBDs?
desflurane > sevofurane > isoflurane > halothane > nitrous oxide-barbiturate-opioid or propofol anesthesia
87
What is the mechanism of action for potentation of inhalational anesthetics and non depolarizing NMBDs?
- Central effect on alpha motorneurons and interneuronal synapsis
- Inhibition of postsynaptic nicotinic acetylcholine receptors
- Augmentation of the antagonist’s affinity at the receptor site
88
What are some antibiotic examples that can potentiate neuromuscular blockade?
Aminoglycoside antibiotics, Polymyxins
| Lincomycin and clindamycin, Tetracyclines
89
What are some Aminoglycoside antibiotic examples that can potentiate neuromuscular blockade?
Gentamycin, Streptomycin, Tobramycin
90
What is the MOA of Lincomycin and clindamycin potentiation of non depolarizing NMBDs?
Primarily inhibit the prejunctional release of acetylcholine and depresses postjunctional nicotinic acetylcholine receptor sensitivity to acetylcholine
91
What is the activity of Tetracyclines potentiation of non depolarizing NMBDs?
Exhibit postjunctional activity only
92
What effect does hypothermia and magnesium sulfate have on nondepolarizing neuromuscular blocking agents?
potentiates the neuromuscular blockade induced by nondepolarizing neuromuscular blocking agents
93
What is the MOA of magnesium on potentiate nondepolarizing neuromuscular blocking agents?
- Mechanism of action may be pharmacokinetic, pharmacodynamic or both
- High magnesium concentrations inhibit calcium channels at the presynaptic nerve terminals that trigger the release of acetycholine
94
What do local anesthetics have on neuromuscular block?
in larger doses potentiate neuromuscular block
95
_________ also potentiates the neuromuscular block
Quinidine
96
What is a factor that makes pts more resistant to nondepolarizing muscle blockers?
Patients receiving chronic anticonvulsant therapy
97
What is the MOA of chronic anticonvulsant therapy on Decreasing Potency of Neuromuscular Blocking Agents?
Attributed to increased clearance, increased binding of the neuromuscular blockers to alpha1 acid glycoproteins, and/or upregulation of neuromuscular acetylcholine receptors
98
What is needed for pts receiving anticonvulsant therapy and need a neuromuscular blockade?
Need increased doses to achieve complete neuromuscular blockade
99
What is the relationship between hyperparathyroidism and hypercalecemia to atracurium?
In patients with hyperparathyroidism, hypercalcemia is associated with decreased sensitivity to atracurium and a resulting shortened duration of neuromuscular blockade
100
What effect does increased calcium have on tubocurarine and pancuronium?
Increased calcium concentrations decrease the sensitivity to tubocurarine and pancuronium
101
What determines the speed of onset of action to to the potency of the nondepolarizing blocker?
The speed of onset of action is inversely proportional to the potency of the nondepolarizing blocker
102
Low potency is predictive of a _______onset
rapid onset (rocuronium)
103
High potency is predictive of a ______ onset
slow onset (tubocurarine)
"Per equipotent doses: more molecules exist in solution for the lower potency drug"
104
What two medications cause autonomic effects?
Tubocurarine & Pancurornium
105
What is the autonomic effects of Tubocurarine?
Associated with marked ganglion blockade resulting in hypotension
106
What is the autonomic effects of Tubocurarine from histamine release? (4)
causes flushing, hypotension, reflex tachycardia, bronchospasm
107
What is the autonomic effects of Pancurornium? (2)
- Direct vagolytic effect
| - May stimulate catecholamine release from adrenergic nerve terminals
108
What three NMBD cause histamine release?
Mivacurium, atracurium, and tubocuranine
109
What are the clinical signs of histamine release? (4)
Skin flushing, decreases in blood pressure, decreases in systemic vascular resistance, increases in heart rate
110
When are clinical signs of histamine release are seen?
when plasma concentrations of histamine increase 200-300% below baseline
111
What is the duration of histamine release?
Short duration of 1-5 minutes, dose related
112
What can occur with histamine release in those with reactive airway disease?
Histamine release may result in increased airway resistance and bronchospasm in patients with reactive airway disease
113
What are the probabilities of Anaphylactic or anaphylactoid reactions during anesthesia?
estimated to occur in 1:1,000 to 1:25,000 administrations
114
What is the mortality rate of Anaphylactic or anaphylactoid reactions?
Associated mortality rate of 5%
115
What immune component is associated with anaphylactic or anaphylactoid reactions?
IgE mediated
116
What is the most common cause of anaphylaxis during anesthesia?
who experienced allergic reactions: neuromuscular blocking drugs > antibiotics
117
What medications are most commonly associated with Anaphylactic reactions?
Succinylcholine and rocuronium most frequently involved
118
____________ and ________ less frequently involved in Anaphylactic reactions.
Pancuronium and cisatracurium
119
Review Neuromuscular Blocking Agent Elimination: Summary
Slide 64
