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Pharmacology Exam 3 > Non-depolarizing Muscle Relaxants > Flashcards

Non-depolarizing Muscle Relaxants Flashcards

1
Q

Name the (4) influences on which Non-depolarizing NMB we chose

A
  1. onset
  2. duration of action
  3. Rate of recovery
  4. metabolism
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2
Q

Non-depolarizing Neuromuscular Blocker MOA

A
  • Act at pre-junctional sites—-To block Ach release
  • Compete for alpha subunits
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3
Q

MOA of NDMB: Compete for alpha subunits

A
  • of post-junctional nChRs
  • with Ach
  • No conformational change
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4
Q

(7) Characteristics of Blockade for Non Depolarizing

A
  1. Decreased twitch response to a single stimulus
  2. Unsustained response (fade) to continuous stimulus
  3. TOF ratio < 0.7
  4. Post-tetanic potentiation
  5. Potentiation of other non-depolarizing drugs
  6. Antagonism by anticholinesterase drugs
  7. No fasciculations during onset
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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
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6
Q

Describe how skeletal muscles contract.

A
  • “all or none”
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7
Q

Name (3) Adverse Side Effects of Non-depolarizing

A
  1. Cardiovascular effects
  2. Critical Illness myopathy
  3. Altered responses
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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
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9
Q

Why do the cardiovascular effects vary between patients?

A
  • underlying diseases
  • preop meds
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10
Q

Are the cardiovascular effects of Non-depolarizing clinically significant?

A
  • Rarely
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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
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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?
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13
Q

Critical Illness myopathy: MOA of skeletal muscle weakness

A

MOA unknown
* Decreased clearance?
* Active metabolites?

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14
Q

Non-depolarizing: Altered Responses with Volatiles

A

Dose-dependent enhancement
* Desflurane>Sevoflurane>Isoflurane
* Onset as early as 30 minutes…

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15
Q

Non-depolarizing + Volatile anesthetics alterations MOA

A
  • Incompletely understood
  • Dose dependent inhibition of nACHR?
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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

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17
Q

Altered Responses (non-depol and SCh): Magnesium

A

Enhances blockade

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18
Q

MOA of action for magnesium + Succinycholine

A
  • MOA is unclear
  • thought to be a more rapid shift to Phase 2 block.
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19
Q

MOA of altered responses with non-depolarizers and Magnesium

A
  • decreases prejunctional release of Ach
  • Decreases sensistivity to post junctional membranes
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20
Q

What can occur when you give Ephedrine prior to non-depolarizers

A
  • Decreases onset time d/t ⬆️ CO and skeletal muscle flow
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21
Q

What occurs when you give Esmolol prior to induction?

A
  • Esmolol delays onset
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22
Q

Altered Response: Hypothermia — Vecuronium and Pancuronium

A
  • doubles the duration
  • MOA: temp slows the hepatic enzymes activity
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23
Q

Altered Response Hypothermia: Atracuium/Cisatracurum

A

MOA: temperature dependent elimination processes
* Hoffman elimination
* Ester hydrolysis

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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
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25
Q

Altered Response: NMB + Acute Hyperkalemia

A
  • Decreases resting membrane potential (partially depolarizes cell membrane)
  • Increases effects of depolarizing NMBDs
  • Resistance to non-depolarizing NMBDs
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26
Q

Altered Response: NMB + Burns

A

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

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27
Q

Altered Resposes: Burns Resistiance to NMB MOA

A
  • Altered affinity of nAChRs?
  • Not related to altered density (# of receptors)
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28
Q

Altered Responses of NMB: Paresis or Hemiplegia— Paretic arm

A
  • Resistance compared to unaffected side
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29
Q

Altered Responses of NMB: Paresis or Hemiplegia— Unaffected side

A
  • Resistance compared to normal patients
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30
Q

Altered Responses: Paresis or Hemiplegia– MOA

A

Proliferation of extrajunctional nAChRs

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31
Q

Altered Responses: Allergic reactions

A
  • Succinylcholine more likely
  • Pavulon, Vecuronium, Rocuronium < Succinylcholine
  • Cisatracurium least likely
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32
Q

Name the Non-depolarizing Agent that will most likely cause an allergic reaction?

A

Succinycholine

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33
Q

Name the Non-depolarizing Agent that will least likely cause an allergic reaction?

A

Cisatracuronium

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34
Q

When is an allergic reaction cross sensitivity possible?

A
  • Quaternary ammonium group
35
Q

What does a 1st exposure represents prior sensitization to what??

A
  • soaps/cosmentics
  • women > men
36
Q

Altered Response to NMB: Gender

A
  • Women more sensitive
  • Need 22% less (vecuronium)
  • Need 30% less (rocuronium)
  • Duration of block greater in women
37
Q

Long-acting NMBDs: Pancuronium (Pavulon)

A
  • Bisquaternary aminosteroid
  • Vagolytic properties
38
Q

Name the most common long acting NMBD

A

Pancuronium (Pavulon)

39
Q

Pancuronium (Pavulon) Intubating dose/onset/Duration

A
  • 0.1 mg/kg
  • onset: 3-5 mins
  • Duration: 60 -90 minutes
40
Q

Pancuronium: Metabolism

A
  • 80% eliminated unchanged in urine
41
Q

Pancuronium: Metabolism in Renal Failure

A
  • 30-50% decreased plasma clearance
  • 10-40% deasacetylpancuronium metabolite ½ as active (by liver)
42
Q

Pancuronium: Metabolism in Liver disease

A
  • Increased VD
  • Larger initial dose is needed
  • Prolonged elimination ½ time
43
Q

Pancuronium: Metabolism– Aging

A

decreased plasma clearnace d/t renal function

44
Q

Pancuronium: Cardiovascular Effects

A

↑ HR, MAP, CO

45
Q

(4) Causes for ↑ HR, MAP, CO from Pancuronium

A
  • Vagal Blockade
  • SNS activation
  • No change in SVR or inotropy
  • No histamine release
46
Q

Cardiovasular Vagal Blockade w/ Pancuronium

A
  • mostly at SA node
  • BP increase d/t HR
47
Q

Cardiovascular SNS activation with Pancuronium

A
  • release of NE presynaptically
  • Blockade of NE uptake
48
Q

Name (4) Intermediate Acting NMBD

A
  • Vecuronium
  • Rocuronium
  • Cisatracurium
  • Atracurium
49
Q

Comparing Local Anesthetics to NMBDs

A
  • similiar onset of maximum blockade
  • Approximartely 1/3 duration of action
  • Minimal/absent CV effects
  • Antagonized by anticholinesterase drugs approx 20 minutes
50
Q

Vecuronium (Norcuron)

A
  • Intermediates -acting
  • Amiosteroid
51
Q

Vercuronium: dose/onset/duration

A
  • 0.2 mg/kg
  • onset: 3-5 minutes
  • duration: 20-35 mintes
52
Q

Vercuronium (Norcuron) Metabolism

A
  • Hepatic metabolism
  • Renal Excretion
53
Q

Vercuronium (Norcuron): Hepatic Metabolism

A
  • Principle organ of elimination
  • 3-desacetylvecuronium
54
Q

Vecuronium metabolite

A
  • 3-desacetylvecuronium
  • 50-80% as potent
  • rapidly converte to metabolite with 1/10th effects
55
Q

Vecuronium (Norcuron): Renal Excretion

A
  • 30% appears unchanged
  • Renal dysfunction — Elimination is prolonged
56
Q

What happens when you give repeated dosed of Vecuronium?

A
  • cumulative effects
57
Q

Vecuronium Metabilism: Elderly

A
  • Decrease Vd –less muscle mass
  • Decrease cleantance– less hepatic flow
58
Q

Vecuronium Metabolism: Obstetrics

A
  • insignificant effects to fetus
  • increased clearnance in 3rd trimester d/t progesterone
  • Prolonged duration early postpartum — IBW
59
Q

Vecuronium + Acid Base Changes

A
  • depends on when the acid-base status changes
  • Prior to NMBD —- no prolonged blockade
60
Q

Vecuronium + Respiratory Acidosis: After NMBD

A

Prolongs the Blockade
* activity inversely proportonal to bound drug —- acidosis decreases bound amount
* change in ionization at receptor increases attachment time.

61
Q

What is you concern post-op with giving acid-base changes following a NMBD?

A
  • hypoventilation
62
Q

Cardiovascular effects of Vecuronium

A
  • Essentially none
  • No histamine release
63
Q

Rocuronium (Zemuron)

A
  • Intermediate acting
  • Aminosteroid
64
Q

Rocuronium: low dose/onset/duration

A
  • 0.6 mg/kg
  • onset: 3-5 minutes
  • duration: 20-30 minutes
65
Q

Recuronium (zemuron): high dose/onset/duration

A
  • 1.2 mg/kg
  • 1-2 minutes
  • duration: 60 minutes
66
Q

Why would you give a high dose of Rocuronium?

A

Large dose parallel onset of SCh but onset of pancuronium

67
Q

Rocuronium ( Zemuron) Metabolism

A
  • Excreted in bile
  • 10-30% renal excretion
68
Q

Rocuronium ( Zemuron) Metabolism: liver failure and elderly

A
  • longer duration
  • d/t decrease clearnace and increased Vd
69
Q

Does renal failure affect the metabolism of Rocuronium?

A
  • only maginally affect
70
Q

Cardiovascular effects of Rocuronium (Zemuron)

A
  • No histamine release
  • No cardiac effects – slight vagolytic effect
71
Q

Cistaracurium (Nimbex)

A
  • Intermediate Acting
  • Benzylisoquinolone
72
Q

Cisatracurium (Nimbex): dose/onset/duration

A
  • 0.1 mg/kg
  • onset 3-5 minutes
  • Duration: 20-35 minutes
73
Q

Cisatracuronium (Nimbex) Metabolism

A
  • Cis-isomer
  • Recovery from infusion is not dependent on time
  • Degradation
74
Q

Degradation of Cisactracuronium (Nimbex)

A
  • Hoffman Elimination
  • Doesn’t use non-specific plasma cholinesterase as much as Atracurium
75
Q

Cisactracuronium (Nimbex): Metabolism in Elderly

A
  • slight delay (1 min) in onset d/t CO
76
Q

Cisactracuronium (Nimbex): Metabolism Obese

A
  • Duration of action prolonged IF dose at actual body weight
  • d/t Vd
77
Q

Cardiovascular Effects of Cisactracuronium (Nimbex)

A
  • No histamine Release
  • Cardiovascular stability
78
Q

Mivacurium (Mivacron)

A
  • Short Acting
  • Benzylisoquinolone
79
Q

Name the only useful Short Acting non-depolarizer

A

Mivacurium (Mivacron)

80
Q

Mivacurium (Mivacron): dose/onset/duration

A
  • 0.15 mg/kg
  • onset: 2-3 minutes
  • Durations: 12-20 minutes
81
Q

Name the (3) steroisomers of Mivacurium (Mivacron)

A
  • Cis-cis
  • Cis-trans
  • Trans-trans

All have NM blocking ability

82
Q

Mivacurium (Mivacron) Metabolism

A
  • Cleared by plasma cholinesterase
  • Not current on market
83
Q

Mivacurium (Mivacron) Cardiovascular Effects

A
  • Minimal effects
  • Histamine Release
84
Q

Mivacurium (Mivacron): CV histamine release

A
  • > 3x ED95 — transicent MAP drop
  • More commone with rapid. large doses
  • MAP drops more in HTN pts than non-HTN pts

Pharmacology Exam 3 (4 decks)

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