Non-depolarizing Muscle Relaxants Flashcards
1
Q
Name the (4) influences on which Non-depolarizing NMB we chose
A
- onset
- duration of action
- Rate of recovery
- metabolism
2
Q
Non-depolarizing Neuromuscular Blocker MOA
A
- Act at pre-junctional sites—-To block Ach release
- Compete for alpha subunits
3
Q
MOA of NDMB: Compete for alpha subunits
A
- of post-junctional nChRs
- with Ach
- No conformational change
4
Q
(7) Characteristics of Blockade for Non Depolarizing
A
- Decreased twitch response to a single stimulus
- Unsustained response (fade) to continuous stimulus
- TOF ratio < 0.7
- Post-tetanic potentiation
- Potentiation of other non-depolarizing drugs
- Antagonism by anticholinesterase drugs
- No fasciculations during onset
5
Q
What does the “fade” suggest in non-depolaring NMB
A
- Suggests some fiber are contracting while some are blocked
- Some are more susceptible to NMBDs
6
Q
Describe how skeletal muscles contract.
A
- “all or none”
7
Q
Name (3) Adverse Side Effects of Non-depolarizing
A
- Cardiovascular effects
- Critical Illness myopathy
- Altered responses
8
Q
Name the (3) reasons for Cardiovascular effects with non-depolarizing
A
- Release of histamine
- Effects at cardiac muscarinic receptors
- Effects on nAChRs at autonomic ganglia
9
Q
Why do the cardiovascular effects vary between patients?
A
- underlying diseases
- preop meds
10
Q
Are the cardiovascular effects of Non-depolarizing clinically significant?
A
- Rarely
11
Q
Non-depolarizing Cardiovascular effects: “Autonomic margin of safety”
A
- Difference between dose that produces blockade (ED95) and dose that creates circulatory effects
- Same dose for pancuronium
- Very different dose for vec, roc, cis
12
Q
Critical Illness Myopathy: Skeletal Muscle Weakness
A
- Weeks to months after NMBD discontinued
- Patients with MSOF who were ventilated > 6 days
- Usually an aminosteroid blocker
- Glucocorticoids prior to NMBD may enhance risk
- Nerve monitoring, sedation, analgesia, small doses of NMBD beneficial?
13
Q
Critical Illness myopathy: MOA of skeletal muscle weakness
A
MOA unknown
* Decreased clearance?
* Active metabolites?
14
Q
Non-depolarizing: Altered Responses with Volatiles
A
Dose-dependent enhancement
* Desflurane>Sevoflurane>Isoflurane
* Onset as early as 30 minutes…
15
Q
Non-depolarizing + Volatile anesthetics alterations MOA
A
- Incompletely understood
- Dose dependent inhibition of nACHR?
16
Q
Altered Responses (non-depolarizers): Diuretics. Corticosteroids, Metoclopromide, LAs
A
Enhances or prolong blockade
* ↑ acetylcholine release
* Depression of cholinesterase activity
* Depression of nerve conduction
17
Q
Altered Responses (non-depol and SCh): Magnesium
A
Enhances blockade
18
Q
MOA of action for magnesium + Succinycholine
A
- MOA is unclear
- thought to be a more rapid shift to Phase 2 block.
19
Q
MOA of altered responses with non-depolarizers and Magnesium
A
- decreases prejunctional release of Ach
- Decreases sensistivity to post junctional membranes
20
Q
What can occur when you give Ephedrine prior to non-depolarizers
A
- Decreases onset time d/t ⬆️ CO and skeletal muscle flow
21
Q
What occurs when you give Esmolol prior to induction?
A
- Esmolol delays onset
22
Q
Altered Response: Hypothermia — Vecuronium and Pancuronium
A
- doubles the duration
- MOA: temp slows the hepatic enzymes activity
23
Q
Altered Response Hypothermia: Atracuium/Cisatracurum
A
MOA: temperature dependent elimination processes
* Hoffman elimination
* Ester hydrolysis
24
Q
Altered Response: Paralytics + Acute Hypokalemia
A
- Hyperpolarizes cell membrane (increased transmembrane potential)
- Resistance to depolarizing NMBDs
- Increased sensitivity to non-depolarizing NMBD’s
25
Altered Response: NMB + Acute Hyperkalemia
* Decreases resting membrane potential (partially depolarizes cell membrane)
* Increases effects of depolarizing NMBDs
* Resistance to non-depolarizing NMBDs
26
Altered Response: NMB + Burns
Resistance
* Begins approx. 10 days post injury
* Declines after 60 days
* 30% BSA or >
* May be offset by using 1.2 mg/kg dose of Rocuronium
27
Altered Resposes: Burns Resistiance to NMB MOA
* Altered affinity of nAChRs?
* Not related to altered density (# of receptors)
28
Altered Responses of NMB: Paresis or Hemiplegia--- Paretic arm
* Resistance compared to unaffected side
29
Altered Responses of NMB: Paresis or Hemiplegia--- Unaffected side
* Resistance compared to normal patients
30
Altered Responses: Paresis or Hemiplegia-- MOA
Proliferation of extrajunctional nAChRs
31
Altered Responses: Allergic reactions
* Succinylcholine more likely
* Pavulon, Vecuronium, Rocuronium < Succinylcholine
* Cisatracurium least likely
32
Name the Non-depolarizing Agent that will most likely cause an allergic reaction?
Succinycholine
33
Name the Non-depolarizing Agent that will least likely cause an allergic reaction?
Cisatracuronium
34
When is an allergic reaction cross sensitivity possible?
* Quaternary ammonium group
35
What does a 1st exposure represents prior sensitization to what??
* soaps/cosmentics
* women > men
36
Altered Response to NMB: Gender
* Women more sensitive
* Need 22% less (vecuronium)
* Need 30% less (rocuronium)
* Duration of block greater in women
37
Long-acting NMBDs: Pancuronium (Pavulon)
* Bisquaternary aminosteroid
* Vagolytic properties
38
Name the most common long acting NMBD
Pancuronium (Pavulon)
39
Pancuronium (Pavulon) Intubating dose/onset/Duration
* 0.1 mg/kg
* onset: 3-5 mins
* Duration: 60 -90 minutes
40
Pancuronium: Metabolism
* 80% eliminated unchanged in urine
41
Pancuronium: Metabolism in Renal Failure
* 30-50% decreased plasma clearance
* 10-40% deasacetylpancuronium metabolite ½ as active (by liver)
42
Pancuronium: Metabolism in Liver disease
* Increased VD
* Larger initial dose is needed
* Prolonged elimination ½ time
43
Pancuronium: Metabolism-- Aging
decreased plasma clearnace d/t renal function
44
Pancuronium: Cardiovascular Effects
↑ HR, MAP, CO
45
(4) Causes for ↑ HR, MAP, CO from Pancuronium
* Vagal Blockade
* SNS activation
* No change in SVR or inotropy
* No histamine release
46
Cardiovasular Vagal Blockade w/ Pancuronium
* mostly at SA node
* BP increase d/t HR
47
Cardiovascular SNS activation with Pancuronium
* release of NE presynaptically
* Blockade of NE uptake
48
Name (4) Intermediate Acting NMBD
* Vecuronium
* Rocuronium
* Cisatracurium
* Atracurium
49
Comparing Local Anesthetics to NMBDs
* similiar onset of maximum blockade
* Approximartely 1/3 duration of action
* Minimal/absent CV effects
* Antagonized by anticholinesterase drugs approx 20 minutes
50
Vecuronium (Norcuron)
* Intermediates -acting
* Amiosteroid
51
Vercuronium: dose/onset/duration
* 0.2 mg/kg
* onset: 3-5 minutes
* duration: 20-35 mintes
52
Vercuronium (Norcuron) Metabolism
* Hepatic metabolism
* Renal Excretion
53
Vercuronium (Norcuron): Hepatic Metabolism
* Principle organ of elimination
* 3-desacetylvecuronium
54
Vecuronium metabolite
* 3-desacetylvecuronium
* 50-80% as potent
* rapidly converte to metabolite with 1/10th effects
55
Vecuronium (Norcuron): Renal Excretion
* 30% appears unchanged
* Renal dysfunction --- Elimination is prolonged
56
What happens when you give repeated dosed of Vecuronium?
* cumulative effects
57
Vecuronium Metabilism: Elderly
* Decrease Vd --less muscle mass
* Decrease cleantance-- less hepatic flow
58
Vecuronium Metabolism: Obstetrics
* insignificant effects to fetus
* increased clearnance in 3rd trimester d/t progesterone
* Prolonged duration early postpartum --- IBW
59
Vecuronium + Acid Base Changes
* depends on when the acid-base status changes
* Prior to NMBD ---- no prolonged blockade
60
Vecuronium + Respiratory Acidosis: After NMBD
Prolongs the Blockade
* activity inversely proportonal to bound drug ---- acidosis decreases bound amount
* change in ionization at receptor increases attachment time.
61
What is you concern post-op with giving acid-base changes following a NMBD?
* hypoventilation
62
Cardiovascular effects of Vecuronium
* Essentially none
* No histamine release
63
Rocuronium (Zemuron)
* Intermediate acting
* Aminosteroid
64
Rocuronium: low dose/onset/duration
* 0.6 mg/kg
* onset: 3-5 minutes
* duration: 20-30 minutes
65
Recuronium (zemuron): high dose/onset/duration
* 1.2 mg/kg
* 1-2 minutes
* duration: 60 minutes
66
Why would you give a high dose of Rocuronium?
Large dose parallel onset of SCh but onset of pancuronium
67
Rocuronium ( Zemuron) Metabolism
* Excreted in bile
* 10-30% renal excretion
68
Rocuronium ( Zemuron) Metabolism: liver failure and elderly
* longer duration
* d/t decrease clearnace and increased Vd
69
Does renal failure affect the metabolism of Rocuronium?
* only maginally affect
70
Cardiovascular effects of Rocuronium (Zemuron)
* No histamine release
* No cardiac effects -- slight vagolytic effect
71
Cistaracurium (Nimbex)
* Intermediate Acting
* Benzylisoquinolone
72
Cisatracurium (Nimbex): dose/onset/duration
* 0.1 mg/kg
* onset 3-5 minutes
* Duration: 20-35 minutes
73
Cisatracuronium (Nimbex) Metabolism
* Cis-isomer
* Recovery from infusion is not dependent on time
* Degradation
74
Degradation of Cisactracuronium (Nimbex)
* Hoffman Elimination
* Doesn't use non-specific plasma cholinesterase as much as Atracurium
75
Cisactracuronium (Nimbex): Metabolism in Elderly
* slight delay (1 min) in onset d/t CO
76
Cisactracuronium (Nimbex): Metabolism Obese
* Duration of action prolonged IF dose at actual body weight
* d/t Vd
77
Cardiovascular Effects of Cisactracuronium (Nimbex)
* No histamine Release
* Cardiovascular stability
78
Mivacurium (Mivacron)
* Short Acting
* Benzylisoquinolone
79
Name the only useful Short Acting non-depolarizer
Mivacurium (Mivacron)
80
Mivacurium (Mivacron): dose/onset/duration
* 0.15 mg/kg
* onset: 2-3 minutes
* Durations: 12-20 minutes
81
Name the (3) steroisomers of Mivacurium (Mivacron)
* Cis-cis
* Cis-trans
* Trans-trans
All have NM blocking ability
82
Mivacurium (Mivacron) Metabolism
* Cleared by plasma cholinesterase
* Not current on market
83
Mivacurium (Mivacron) Cardiovascular Effects
* Minimal effects
* Histamine Release
84
Mivacurium (Mivacron): CV histamine release
* > 3x ED95 --- transicent MAP drop
* More commone with rapid. large doses
* MAP drops more in HTN pts than non-HTN pts
