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Pharmacology Exam 2 > IV Anesthetics > Flashcards

IV Anesthetics Flashcards

1
Q

What is the chemical name for Propofol?

A

2,6-diisopropylphenol

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2
Q

What preservatives are found in the generic formulation of Propofol and what are the clinical implications?

A

sodium metabisulfite-bronchospasm
benzyl alcohol-avoid in infants

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3
Q

What is the mechanism of action of Propofol?

A

direct GABA-A agonist
change in Cl- conductance
neuronal hyperpolarization

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4
Q

What is the dose of propofol for induction? Infusion?

A

Induction: 1.5-2.5 mg/kg
Infusion: 25-200 mcg/kg/min

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5
Q

What is the onset of propofol?

A

30-60 seconds

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6
Q

What is the duration of propofol?

A

5-10 minutes

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7
Q

How is propofol cleared?

A

Liver P450 enzymes and extrahepatic metabolism mostly in the lungs
*clearance exceeds liver blood flow

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8
Q

What is the active metabolite of propofol?

A

none

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9
Q

What are the cardiovascular effects of propofol?

A

decreased BP, SVR, venous tone, preload, myocardial contractility

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10
Q

What are the respiratory effects of propofol?

A

shifts CO2 curve down and to the right (less sensitive to CO2)
respiratory depression
inhibits hypoxic ventilatory drive

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11
Q

What are the CNS effects of Propofol?

A

decreased CMRO2, CBF, ICP, IOP
NO ANALGESIA
anticonvulsant properties
myoclonus may occur
rarely seizures may occur

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12
Q

What are some other properties of propofol that are relevant?

A

antioxidant properties
change the color of urine (green-phenol, cloudy-increased uric acid)
antipruritic: 10 mg IV (spinal opioids and cholestasis)
antiemetic: 10-20 mg

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13
Q

What are the risk factors for propofol infusion syndrome?

A

propofol dose >4 mcg/kg/hr
propofol infusion duration >48 hours
sepsis
continuous catecholamine infusions
high dose steroids
significant cerebral injury

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14
Q

What are the clinical signs of propofol infusion syndrome?

A

acute refractory bradycardia leading to asystole plus at least one:
-metabolic acidosis
-rhabdomyolysis
-enlarged or fatty liver
-renal failure
-hyperlipidemia
-lipemia (early sign)

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15
Q

How do you treat propofol infusion syndrome?

A

discontinue propofol, maximize gas exchange, cardiac pacing, PDE inhibitors, glucagon, ECMO, CRRT

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16
Q

How long is a propofol syringe good for? Tubing?

A

syringe: 6 hours
tubing: 12 hours

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17
Q

What is the chemical name for fospropofol?

A

phosphono-O-methyl-2,6-diisopropylphenol

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18
Q

How does the formulation of Fospropofol differ from Propofol?

A

made in an aqueous solution which prevents burning and doesn’t support microbial growth

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19
Q

What is Fospropofol’s mechanism of action?

A

-prodrug metabolized to Propofol by alkaline phosphatase
-GABA-A agonist

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20
Q

What is the dose of Fospropofol?

A

initial bolus: 6.5 mg/kg
repeat bolus: 1.6 mg/kg

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21
Q

What is the onset of Fospropofol?

A

5-13 minutes

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22
Q

What is the duration of Fospropofol?

A

15-45 minutes

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23
Q

How is Fospropofol cleared?

A

same as propofol
liver P450 enzymes and extrahepatic metabolism mostly in the lungs

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24
Q

What is Fospropofol metabolized into?

A

Propofol, formaldehyde, and phosphate

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25
Q

What is a major side effect of Fospropofol?

A

genital and anal burning

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26
Q

What is the chemical name for ketamine?

A

2-(o-cholophenyl)-2 (methylamino) cycloheanone hydrochloride

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27
Q

What medication class is Ketamine from?

A

arylcyclohexylamine

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28
Q

What is the formulation for Ketamine?

A

racemic mixture of 1, 5, or 10% solutions

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29
Q

What is the mechanism of action for Ketamine?

A

NMDA receptor antagonist (antagonizes glutamate)
secondary receptors: opioid, MAO, serotonin, NE, muscarinic, Na+ channels

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30
Q

What is the dose of Ketamine?

A

induction: 1-2 mg/kg
maintenance: 1-3 mg/kg
analgesia: 0.1-0.5 mg/kg
IM: 4-8 mg/kg
PO: 10 mg/kg

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31
Q

What is the onset of Ketamine?

A

IV: 30-60 seconds
IM: 2-4 minutes
PO: variable

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32
Q

What is the duration of Ketamine?

A

10-20 minutes
(60-90 minutes to full orientation)

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33
Q

How is Ketamine cleared?

A

liver P450 enzymes

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34
Q

What effect does chronic ketamine use have?

A

induces the enzymes that metabolize it leading to rapid escalation in tolerance

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35
Q

What is the active metabolite of Ketamine?

A

Norketamine (1/3-1/5 potency)
excreted in the urine

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36
Q

What are the cardiovascular effects of Ketamine?

A

increased SNS tone, CO, HR, SVR, PVR
myocardial depressant

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37
Q

What are the respiratory effects of Ketamine?

A

bronchodilation
increased oral and pulmonary secretions
no effect on upper airway muscle tone, airway reflexes, respiratory drive, CO2 response curve

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38
Q

What are the CNS effects of Ketamine?

A

increased CMRO2, ICP, CBF, & EEG activity
possible increased IOP
nystagmus or blepharospasm
emergence delirium (prevent w/benzos)

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39
Q

True or False: Ketamine relieves somatic pain more than visceral pain.

A

True

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40
Q

What is the chemical name for Etomidate?

A

R-1-methyl-1-(a-methylbenzyl) imidazole -5-carboxylate

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41
Q

What medication class is Etomidate from?

A

Imidazole

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42
Q

When given in physiologic pH, is Etomidate more lipid or water-soluble?

A

lipid soluble

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43
Q

What are the two formulations of Etomidate?

A

35% Propylene glycol (more painful)
lipid emulsion (less painful)

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44
Q

What is the mechanism of action of Etomidate?

A

GABA-A agonist

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45
Q

What is the dose of Etomidate?

A

0.2-0.4 mg/kg

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46
Q

What is the onset of Etomidate?

A

30-60 seconds

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47
Q

What is the duration of Etomidate?

A

5-15 minutes

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48
Q

How is Etomidate cleared?

A

Liver (P450 enzymes) & non-specific plasma esterases

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49
Q

True or False: With Etomidate, rapid awakening is due to redistribution.

A

True

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50
Q

What is the active metabolite of Etomidate?

A

none

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51
Q

What are the cardiovascular effects of Etomidate?

A

minimal change in HR, SV, & CO
decreased SVR & BP
no block to SNS from laryngoscopy

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52
Q

What are the respiratory effects of Etomidate?

A

mild respiratory depression

53
Q

What are the CNS effects of Etomidate?

A

decreased CMRO2, CBF, ICP
cerebral perfusion pressure same
NO ANALGESIA

54
Q

Does Etomidate increase the risk of seizures?

A

no hx of seizures: no increased risk
hx of seizures: increased risk of seizures and seizure-like activity

55
Q

Why is Etomidate use avoided in patients with Addison’s disease or sepsis?

A

Etomidate inhibits 11-beta-hydroxylase and 17-beta-hydroxylase which are required for cortisol and aldosterone synthesis

56
Q

True or False: Nausea and vomiting rates are more common with Etomidate than with other induction agents.

A

True
as high as 30-40%

57
Q

What are thiobarbiturates?

A

sulfur molecule in the 2nd position
increases lipid solubility & potency
ex. Thiopental, Thiamylal

58
Q

What are oxybarbiturates?

A

oxygen molecule in the 2nd position
ex. Methohexital, Pentobarbital

59
Q

What does adding a methyl group to the nitrogen of barbiturates do?

A

lowers the seizure threshold and increases potency
ex. Methohexital

60
Q

What does adding a methyl group to the nitrogen of barbiturates do?

A

decreases seizure threshold and increases potency
ex. Methohexital

61
Q

What is the chemical name for Thiopental?

A

5-ethyl-5-(1-methylbutyl)-2-thiobarbituric acid

62
Q

What medication class does Thiopental come from?

A

barbiturate

63
Q

What is the formulation of Thiopental?

A

water soluble
precipitates when mixed with acidic solution

64
Q

What is the mechanism of action of Thiopental?

A

GABA-A agonist
low dose: increases affinity for GABA for receptor
high dose: directly stimulates GABA-A receptor

65
Q

What is the dose for Thiopental?

A

adults: 2.5-5 mg/kg
peds: 5-6 mg/kg

66
Q

What is the onset of Thiopental?

A

30-60 seconds

67
Q

What is the duration of action of Thiopental?

A

5-10 minutes

68
Q

How is Thiopental cleared?

A

Liver (P450 enzymes)
*repeated doses>tissue accumulation>prolonged wake up and hangover effect

69
Q

True or False: With Thiopental, rapid awakening is determined by redistribution.

A

True

70
Q

What is the active metabolite of Thiopental?

A

low dose: none
high dose: Pentobarbital

71
Q

What are the cardiovascular effects of Thiopental?

A

hypotension (vasodilation, decreased preload, myocardial depression)
reflex tachycardia (maintains CO)

72
Q

What are the respiratory effects of Thiopental?

A

shifts CO2 curve to right
respiratory depression
bronchoconstriction (histamine release)

73
Q

What are the CNS effects of Thiopental?

A

decreased CMRO2, CBF, ICP, EEG
NO ANALGESIA
focal neuroprotection

74
Q

What occurs with intra-arterial injection of Thiopental?

A

intense vasoconstriction, crystal formation, inflammation > tissue necrosis

75
Q

How do you treat intra-arterial injection of Thiopental?

A

phentolamine or phenoxybenzamine
stellate ganglion block or brachial plexus block

76
Q

Which barbiturate is the gold standard for electroconvulsive therapy? What is the dose?

A

Methohexital
1-1.5 mg/kg

77
Q

Which barbiturate is excreted unchanged in the urine?

A

Phenobarbital
*not metabolized by P450 enzymes

78
Q

What is acute intermittent porphyria?

A

caused by a defect in heme synthesis that promotes the accumulation of heme precursors

79
Q

What is AIP made worse by?

A

stimulation of ALA synthase
emotional stress
prolonged NPO status
CYP450 induction

80
Q

What are the signs and symptoms of AIP?

A

severe abdominal pain
N/V
anxiety/confusion/psychosis
coma
skeletal muscle weakness
bulbar weakness

81
Q

What drugs should be avoided in patients with AIP?

A

barbiturates
etomidate
ketamine
ketorolac
amiodarone
calcium channel blockers
birth control pills

82
Q

How do you treat AIP?

A

HYDRATION
glucose supplementation
heme arginate
prevent hypothermia

83
Q

What drugs are safe in patients with AIP?

A

volatile anesthetics
nitrous oxide
NMBs
NMB reversals
narcotics
midazolam
ondansetron
vasopressors
beta-blockers

84
Q

What is the chemical name for Dexmedetomidine?

A

(S)-4-(1-(2,3-dimethylphenyl)ethyl)-1H-imidazole monohydrochloride

85
Q

What medication class is Dexmedetomidine from?

A

Imidazole

86
Q

What is the formulation of Dexmedetomidine?

A

water soluble
Vial: 100 mcg/mL
Infusion: 4 mcg/mL

87
Q

What is the mechanism of action of Dexmedetomidine?

A

alpha-2 agonist of presynaptic nerve
sedation: inhibits the locus coerulus in the pons
analgesia: dorsal horn of spinal cord

88
Q

What is the dose of Dexmedetomidine?

A

loading: 1 mcg/kg over 10 minutes
maintenance: 0.4-0.7 mcg/kg/hr

89
Q

What is the onset of Dexmedetomidine?

A

10-20 minutes with loading dose

90
Q

What is the duration of Dexmedetomidine?

A

10-30 minutes after infusion stopped

91
Q

How is Dexmedetomidine cleared?

A

Liver (P450 enzymes)

92
Q

What is the active metabolite of Dexmedetomidine?

A

none

93
Q

What are the cardiovascular effects of Dexmedetomidine?

A

hypotension
bradycardia

94
Q

What side effect does rapid administration of Dexmedetomidine cause?

A

short-lived hypertension
alpha-2 stimulation in vasculature before SNS tone reduction in CNS

95
Q

What are the respiratory effects of Dexmedetomidine?

A

NO respiratory depression

96
Q

What are the CNS effects of Dexmedetomidine?

A

decreased CBF
ANALGESIA
NO change: CMRO2, ICP
resembles sleep
not reliable amnestic
anti-shivering (impairs thermoregulatory response)

97
Q

Why is Dexmedetomidine good for neuro surgery?

A

does not impair evoked potentials
useful for “wake-up” test for scoliosis

98
Q

How can you give Dexmedetomidine to a child without an IV?

A

nasal or buccal route
3-4 mcg/kg 1 hour before surgery

99
Q

What is the chemical name for Midazolam?

A

8-chloro-6-(2-fluorophenyl)-1-methyl-4-H-imidazo(1,5-a)(1,4) benzodiazepine

100
Q

What medication class is Midazolam from?

A

Benzodiazepine

101
Q

What is the formulation of Midazolam?

A

imidazole ring

102
Q

When given in physiologic pH, is Midazolam more lipid or water-soluble?

A

lipid soluble

103
Q

What is the mechanism of action of Midazolam?

A

GABA-A agonist
increased frequency of channel opening

104
Q

What is the dose of Midazolam?

A

IV sedation: 0.01-0.1 mg/kg
IV induction: 0.1-0.4 mg/kg
PO sedation peds: 0.5-1 mg/kg

105
Q

What is the onset of Midazolam?

A

30-60 seconds

106
Q

What is the duration of action of Midazolam?

A

IV: 20-60 minutes

107
Q

How is Midazolam cleared?

A

Liver and intenstine by P450 enzymes

108
Q

What is the active metabolite of Midazolam?

A

1-hydroxymidazolam
1/2 potent, rapidly conjugated to inactive
renal failure prolongs the effect

109
Q

What are the cardiovascular effects of Midazolam?

A

minimal effects for sedation
decreased SVR and BP for induction

110
Q

What are the respiratory effects of Midazolam?

A

minimal effects for sedation
respiratory depression for induction (COPD patients more sensitive)
opioids potentiate respiratory depression

111
Q

What are the CNS effects of Midazolam?

A

minimal effects on CMRO2 & CBF for sedation
decreased CMRO2 and CBF for induction
anterograde amnesia
anticonvulsant
anxiolysis
spinally mediated skeletal muscle relaxation
NO ANALGESIA

112
Q

Why does Diazepam remain in the body for so long?

A

undergoes enterohepatic recirculation
t1/2=43 hours

113
Q

What are good uses for Diazepam?

A

anticonvulsant
prevention of emergence delirium after ketamine
antispasmodic (muscle spasticity)

114
Q

Why is Lorazepam limited for being an anticonvulsant?

A

it has a slow onset

115
Q

What is the relative potency (greatest to least):
diazepam
lorazepam
midazolam

A

lorazepam > midazolam > diazepam
LMD sounds like L & D

116
Q

What is added to diazepam and lorazepam to enhance water solubility?

A

Propylene glycol
*causes venous irritation (diazepam > lorazepam)

117
Q

What is the dose for remimazolam?

A

induction: 2.5-5 mg over 1 minute for
maintenance: 2.5 mg over 15 seconds Q2min

118
Q

What is the half-time of Remimazolam?

A

0.5-2 minutes

119
Q

How is Remimazolam cleared?

A

non-specific plasma esterases

120
Q

What are the benefits of Remimazolam over Midazolam?

A

faster onset of action, deeper sedation, faster recovery

121
Q

What are the benefits of Remimazolam over Propofol?

A

less respiratory depression and better cardiopulmonary stability

122
Q

What is the reversal for Remimazolam?

A

Flumazenil

123
Q

What is the mechanism of action of Flumazenil?

A

competitive GABA-A antagonist

124
Q

What is the duration of action of Flumazenil?

A

30-60 minutes

125
Q

What is the dose of Flumazenil?

A

initial: 0.2 mg IV
0.1 mg increments Q1min

126
Q

How is reversal of benzodiazepines different from reversal of opioids?

A

Flumazenil does NOT increase SNS tone, anxiety, or neuroendocrine evidence of stress

127
Q

What side effects can occur when giving Flumazenil to a benzodiazepine-dependent patient?

A

signs of withdrawal including seizures

128
Q

True or False: Flumazenil usually reverses sedative effects with greater effect than amnestic effects.

A

True

Pharmacology Exam 2 (5 decks)

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