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Anesthesia Pharmacology Review > Induction Drugs Pt. I (Barbiturates, Propofol) > Flashcards

Induction Drugs Pt. I (Barbiturates, Propofol) Flashcards

1
Q

Describe a sedative agent

A

Drug that induces a state of calm or sleep.

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2
Q

Describe a hypnotic agent

A

A drug taht induces hypnosis or sleep.

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3
Q

Describe an anxiolytic agent.

A

A drug that reduces anxiety and that has sedation as a side effect.

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4
Q

Describe a sedative-hypnotic agent.

A

A drug that reversibly depress activity of the CNS.

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5
Q

Describe general anesthesia.

A

A state of drug-induced unconsciousness.

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6
Q

What are other names for Procedural Sedation?

A

Conscious Sedation
Monitored Anesthesia Care

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7
Q

Describe Monitored Anesthesia Care

A

Administration of a combination
of sedative(s) and analgesic(s) to induce a depressed level of consciousness, allowing patients to tolerate unpleasant procedures and enabling clinicians to perform procedures effectively.

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8
Q

What four groups will medication be distributed to?

What is the CO% of each group?

A

Vessel rich group (75%)
Muscle group (18%)
Fat (5%)
Vessel poor group (2%)

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9
Q

What makes up the Vessel-rich group?

A

Brain
Heart
Kidney
Liver

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10
Q

What makes up the Muscle group?

A

Skeletal muscle
Skin

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11
Q

What makes up the Vessel-poor group?

A

Bone
Tendon
Cartilage

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12
Q

What are the 5 components of General Anesthesia?

A
  • Hypnosis
  • Analgesia
  • Muscle Relaxation
  • Sympatholysis (hemodynamic stability)
  • Amnesia

When giving general anesthesia, we want these 5 things to occur

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13
Q

What are the 4 stages of General Anesthesia?

A

Stage 1: Analgesia
Stage 2: Delirium
Stage 3: Surgical Anesthesia
Stage 4: Medullary Paralysis

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14
Q

What stage can cause death?

A

Stage 4

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15
Q

What stage consists of the lightest level of anesthesia?

A

Stage 1

(This is the stage of conscious sedation, the patient can still open their eyes on command, breathe normally, and protective reflexes maintained.)

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16
Q

Stage 1 begins with the initiation of an anesthetic agent and ends with ___.

The patient will experience ___ and ___ depression.

A

Loss of consciousness
Sensory and mental

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17
Q

What are the 3 lower airway reflexes?

A

Coughing
Gagging
Swallowing

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18
Q

What is the upper airway reflex?

A

Sneezing

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19
Q

Stage 2 starts with the loss of consciousness to the onset of automatic rhythmicity of vital signs. This stage is characterized by excitement in what areas?

A
  • Undesired CV instability excitation
  • Dysconjugate ocular movements
  • Laryngospasm
  • Emesis.
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20
Q

What is the response to stimulation in Stage 2 like?

A

Exaggerated and violent

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21
Q

What stage will have an absence of response to surgical incision and depression in all elements of the nervous system?

A

Stage 3

Will have all 5 components of anesthesia hypnosis, analgesia, muscle relaxation, sympatholysis, and amnesia

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22
Q

What stage is associated with cessation of spontaneous respiration and medullary cardiac reflex? What are the symptoms of this stage?

A

Stage 4 (over anesthesia)

  • All reflexes are absent
  • Flaccid Paralysis
  • Marked Hypotension with w/ irregular pulse.
  • May lead to death
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23
Q

How can you tell if a patient is out from stage 2 to stage 1 for an awake extubation?

A

Patient is able to follow commands

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24
Q

What is the benefit of using a barbiturate (thiopental) vs. diethyl ether?

A

Diethyl ether is slow, unpleasant, and more dangerous for induction of general anesthesia.
Barbiturates can cover stages 1 to stage 3 in as little as 2 minutes.

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25
Q

Why are barbiturates no longer used in the U.S.?

A

Thiopental is now part of the lethal injection cocktail for capital punishment.

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26
Q

Why are we still talking about barbiturates?

A

This drug is still used in other countries.
Critical to understand properties of barbiturates (gold standard) as comparison with other drugs.

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27
Q

What is the MOA of Barbituates?

A

Potentiates GABA-A channel activity; directly mimics GABA.

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28
Q

What receptors do barbiturates act on?

A

Glutamate
Adenosine
Neuronal nAChRs

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29
Q

Barbiturates are a cerebral ____.

What will be the effect on CBF?
What will be the effect on CMRO2?

A

Vasoconstrictors

CBF decreases
CMRO2 decreases by 55%

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30
Q

How do barbiturates help with seizures?

A

The decrease in CBF and CMRO2 will decrease the metabolic activity of the brain

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31
Q

Do barbiturates cause analgesic effects?

A

No

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32
Q

What is the onset time of barbiturates?

A

30 seconds

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33
Q

Barbiturates have a rapid redistribution from brain to other tissues.
At 5 minutes ___ of the total dose in the blood is redistributed.
At 30 minutes __ of the total dose is remaining.

A

50%
10%

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34
Q

What will result from a prolonged infusion time of barbiturates?

A

Lengthy context-sensitive half-time

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35
Q

Where is thiopental rapidly distributed to?

The rate of metabolism of thiopental is equal to what?

A

Thiopental goes to the brain and viscera in about 1 minute.

Metabolism of thiopental is equal to thiopental accumulation in the fat.

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36
Q

During emergence, the medication that was stored in the _________ and __________ will be reabsorbed in the blood and affect mentation.

A

fat
lean tissues

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37
Q

What is the site of the initial redistribution for barbiturates?
After how much time is equilibrium achieved to the plasma?

A

Skeletal muscles
15 minutes

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38
Q

Why is the context-sensitive half-time for barbituates so long?

A

The fat is a reservoir site for the drug, redosing/large dosing will yield cumulative effects.

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39
Q

Usually, barbiturates are dosed on ___ body weight.

A

lean

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40
Q

How are Barbituates metabolized?

How are they excreted?

Elimination half-time consideration for pediatrics?

A

Hepatocytes 99%

Renally

Shorter half-time (higher metabolism)

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41
Q

What is the protein binding percentage of barbiturates?

Is the barbiturate active or inactive?

A

Binds to albumin 70 to 85%

Inactive, most of the drug will be bound to the protein. Once the drug becomes unbound and crosses the BBB, that is when the drug will affect mentation.

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42
Q

When the barbiturate is non-ionized it will be ____ soluble and ____ favors.

A

more lipid soluble and acidosis favors

Wants to stay in muscle and fat

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43
Q

When the barbiturate is ionized, it will be ____ soluble and ____ favors.

A

less lipid soluble and alkalosis favors

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44
Q

What are previous uses of barbiturates?

A

Premedication for Hangover

Grand mal seizures (now uses benzos)

Rectal administration with uncooperative/young patients

Increased ICP, cerebral protection

Induction

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45
Q

___ isomer is much more potent than ____ isomer, but the barbiturates are only marketed as ____ mixtures.

A

S- isomer
R- isomer
Racemic Mixture

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46
Q

What are examples of oxybarbiturates?

A

Methohexital
Phenobarbital
Pentobarbital

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47
Q

What are examples of thiobarbiturates?

A

Thiopental
Thiamylal

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48
Q

What is the dose of Thiopental (sodium pentothal)

A

4mg/kg IV

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49
Q

For Thiopental, in 30 minutes only ___% remains in the brain.

A

10%
(rapid redistribution)
Because of the rapid redistribution, be sure to supplement induction with other anesthetic agents so the patient can stay down during induction.

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50
Q

Where else can thiopental be redistributed?

When do you decrease the dose of thiopental?

A

Skeletal muscles

In the elderly or if the patient is in shock

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51
Q

What is the fat/blood coefficient of thiopental?

The dose of thiopental is calculated on _________.

The elimination half-time of thiopental is longer than __________.

A

11

Ideal body weight

Methohexital

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52
Q

Describes the distribution of a given agent at equilibrium between two substances at the same temperature, pressure, and volume.

A

Partition coefficient

50% of thiopental is available in arterial blood and 50% is available in the vessel poor group, rich group, and muscle, since they are at equilibrium that will be the partition coefficient

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53
Q

Describes the distribution of an anesthetic between blood and gas at the same partial pressure.

A

Blood-gas coefficient

54
Q

What does a higher blood-gas coefficient correlate with?

A

Higher solubility of anesthetic in the blood and thus slowing the rate of induction. The blood can be considered a pharmacologically inactive reservoir.

55
Q

Methohexital (Brevital) has a lower lipid solubility than ___________.

A

Pentothal (Thiopental)

56
Q

At a normal pH, __% of methohexital is non-ionized.
What percent of pentothal is non-ionized?

What is the metabolism and recovery of methohexital?

A

76%
61% (pentothal)

Fast metabolism and rapid recovery
(induction only, not continuous infusion)

57
Q

What are the excitatory phenomenon with methohexital?

A

Myoclonus
Hiccups

58
Q

What is the IV dose of methohexital?

What is the rectal dose of methohexital?

A

1.5 mg/kg IV

20-30 mg/kg (rectal)

59
Q

With continuous methohexital infusion, there can be post-op ____ activity in 1 out of 3 patients.

A

Seizure

60
Q

Methohexital can induce seizures in patients undergoing _ _ _.

A

temporal lobe resection
(lower seizure threshold, easier for seizures to occur)

61
Q

Methohexital will decrease seizure durations by __% in ECT patients

A

35 to 45%

don’t give methohexital if the patient has a history of seizures, but if they are in an active seizure, go ahead and use methohexital

62
Q

CV effects of barbiturates
(5mg/kg of thiopental)
SBP:
HR:

A

SBP: Transient 10-20 mmHg decrease
HR: 15 to 20 bpm increase

63
Q

For patients that are hypovolemic, have CHF, and are on beta blockers. Barbiturates will lack __ response.

A

baroreceptor

just don’t give barbiturates to anyone with these conditions

64
Q

Barbiturates will cause __ release.
Usually asymptomatic, thiopental can lead to an anaphylactoid response with previous exposure.

A

Histamine

have epinephrine ready

65
Q

What are the side effects of ventilation with barbiturates?

A

Dose-dependent.
The increasing dose will depress ventilatory centers (medullary and pontine).

66
Q

Barbiturates and sensitivity to CO2.

A

Decrease sensitivity to CO2.
This means we need a higher level of ETCO2 in order to trigger the medullary and pointe center for spontaneous respiration.

May need an ETCO2 of 50 or 55 to trigger a breath

67
Q

How do you return to spontaneous ventilation with barbiturates?

A

Slow frequency or decrease tidal volume.

68
Q

What occurs with barbiturates through an intra-arterial injection?

A

Immediate intense vasoconstriction and pain.
Obscure distal arterial pulses.
Blanching, followed by cyanosis.
Gangrene and permanent nerve damage.

69
Q

How do you treat intra-arterial barbiturate injection?

A

Vasodilators - lidocaine and papaverine to sustain adequate blood flow (heat pads)

70
Q

Scoliosis surgery with barbiturates will require ______ monitoring

A

Somatosensory Evoked Potentials (SSEP)

Commonly used to detect changes in nerve conduction and prevent impending nerve injury

71
Q

After 2-7 days barbiturates cause _ _.

A

Enzyme induction

Accelerated metabolism of anticoagulants, phenytoin, TCAs, digoxin, corticosteroids, bile salts, and vit. K.
May persist for 30 days

72
Q

Barbituates will cause a modest transient decrease in _ _ _ and _ _ _.

A

Renal blood flow
Glomerular filtration rate

73
Q

Propofol is a __ __ __ agonist.

A

Gamma Aminobutyric Acid (GABA) agonist

74
Q

What is the dose of propofol for induction?

A

1.5 to 2.5 mg/kg IV

75
Q

What is the dose of propofol for conscious sedation?

A

25 to 100 µg/kg/min

76
Q

What is the dose of propofol for maintenance?

A

100 to 300 µg/kg/min

77
Q

Rapid injection ( < 15 secs) of propofol will produce unconsciousness within _ _.

A

30 seconds

78
Q

Propofol is a constitution of 1% solution, how many mg/mL is that?

What would 2% be?

A

1% (10mg/mL)

2% (20mg/mL)

79
Q

What is the constitution of 1% Propofol?

A

10% soybean oil
2.25% glycerol
1.2% purified egg phospatide (lecithin)
Assess patient allergy to egg whites

80
Q

What are the disadvantages of Propofol?

A

Support bacterial growth
Increase plasma triglyceride conc.
Pain on injection

81
Q

What are the commercial preparations for propofol?

A

Ampofol
Aquavan
Nonlipid with Cyclodextrins (clinical trials)

82
Q

Describe Ampofol preparation

A

Low lipid emulsions with no preservatives
Higher incidence of pain on injection

83
Q

Describe Aquavan preparation

A

Prodrug that eliminates pain on injection
Byproduct will produce pain, larger Vd, and higher potency

84
Q

Propofol is a relative modulator of ____ receptors.

A

GABA-A

85
Q

What is the principal inhibitory neurotransmitter of the brain?

A

GABA

86
Q

GABA-A receptor activation will increase transmembrane conductance of what ion?

A

Chloride
hyperpolarization of the postsynaptic cell membrane and functional inhibition of the postsynaptic neuron

87
Q

Immobility of propofol is not caused by drug-induced __ __ __.

A

spinal cord depression

88
Q

Clearance of propofol is through the ________ more than hepatic blood flow.

A

Lungs

89
Q

Tissue uptake of propofol is greater when it is being metabolized by _________.

A

Cytochrome P450

90
Q

What metabolizes propofol?

What does it metabolize to?

Where is propofol excreted?

A

Hepatic enzyme cytochrome P450

Water soluble sulfate and glucuronic acid metabolites

Excreted by the kidneys

91
Q

What is the elimination half-time of propofol?

What is the context-sensitive half-time of propofol?

A

0.5 to 1.5 hours

40 minutes (8-hour infusion)
Note that it is shorter than thiopental, b/c propofol is not as lipid-soluble as barbiturates

92
Q

How will cirrohsis of the liver affect propfol administration?

A

Similar awakening time with alcoholic and normal patients

93
Q

Does renal dysfuntion affect propofol clearance?

A

No

94
Q

What concerns are there regarding propofol and pregnancy?

A

Propofol will cross the placenta but is rapidly cleared in the neonatal circulation

95
Q

What are the clinical uses of propofol?

A

Induction
Continous IV infusion

96
Q

In ICU, _____-% solution is used to reduce the amount of lipid emulsion administered.

A

2%
(20 mg/mL)

97
Q

What is the propofol induction dose for adults?

A

1.5 to 2.5 mg/kg IV

98
Q

What is the propofol induction dose for children?

A

3.0 to 3.5 mg/kg IV
higher dose d/t larger central distribution volume and clearance rate

99
Q

Propofol dose consideration for the elderly?

A

Lower induction dose by 25% to 50%
1 mg/kg or even less than that.

100
Q

Plasma levels of propofol
Unconscious on induction:
Awakening:

A

Unconscious on induction: 2 to 6 μg/mL
Awakening: 1.0 to 1.5 μg/mL

101
Q

What is the propofol dose for conscious sedation?

A

25 to 100 µg/kg/min

102
Q

With intravenous sedation of propofol:
____ analgesic and amnestic effects.
Prompt recovery without ___ ___.
Low incidence of ___.
Anti-convulsant and ___ properties.
___ or ____ used as adjuncts.

A

Minimal
Residual sedation
PONV
Amnestic (dose-dependent)
Midazolam or Opioids

103
Q

Propofol is the agent of choice in brief ___ ____ procedures.

A

GI Endoscopy

104
Q

The anti-emetic effects of propofol are more effective than _______.

What is propofol’s MOA for its anti-emetic effect?

A

Zofran
Depresses the subcortical pathways and has a direct depressant effect on the vomiting center.

105
Q

What is the sub-hypnotic dose of propofol?

How many mL is that?

A

10 to 15 mg IV followed by 10 μg/kg/min

1 to 1.5 mL of 1% proprofol

106
Q

Propofol also has anti-pruritic effects, what is the dose?

How much will you give if you have 1% propofol?

A

10 mg IV

1% propofol is 10mg/mL so 1 mL.

107
Q

Propofol can be used as an anticonvulsant agent, what is the dose?

A

1 mg/kg IV

108
Q

What other benefits does Propofol have?

A

Bronchodilator
Analgesic (at low doses)
Potent antioxidant
Does not trigger MH

109
Q

With Propofol what occurs to CMRO2, CBF, and ICP?

A

Decrease
Autoregulation related to CBF and PaCO2 is maintained

110
Q

Large doses of Propofol may cause a _ in cerebral perfusion pressure

A

decrease
support the MAP

111
Q

EEG changes from propofol is similar to ___.

A

Thiopental

112
Q

What are SSEPs?

Propofol effect on SSEPs?

A

Somatosensory evoked potentials (SSEPs) are brain and spinal cord responses elicited by sensory stimuli. Most of the clinically used SSEPs are elicited by electrical stimulation to the peripheral nerve, although more natural stimuli such as pain or touch sensation can yield SSEPs.

Propofol has no SSEP suppression, unless volatiles or nitrous is added.

113
Q

Propofol does cause excitatory movements on induction/emergency (myoclonus) but does not produce ____.

A

Seizures

114
Q

Does SBP decrease more with Propofol or Thiopental administration?

A

Propofol
d/t inhibition of SNS, vascular smooth muscle relaxation, and decreased SVR. Also decreases the level of intracellular calcium

115
Q

What are the CV side effects if propofol is given to someone with hypovolemia, elderly, or LV compromise?

A

Exaggerated
(might consider etomidate instead)

116
Q

What is the effect on HR with propofol?

A

Bradycardia d/t decreased SNS response, may depress baroreceptor reflexes.

Profound bradycardia and asystole happens even in healthy adults.

Worse in the pediatric population

117
Q

What occurs to ventilation with Propofol administration?

A

Dose-dependent depression, apnea
increased with opioids (synergistic)

118
Q

What occurs to the hypoxic pulmonary vasocontriction response with Propofol?

A

Remains intact
Prevents V/Q mismatch; maintaining CBF and CMRO2

119
Q

What can reverse the ventilatory depressive effects of Propofol?

A

Painful surgical stimulation

120
Q

Propofol’s effect on liver transaminase enzymes or creatine concentration:

A

Normal

121
Q

Prolonged propofol infusion can cause _ injury

A

Hepatocellular

122
Q

This syndrome will cause green urine (from phenols), and no alternation in renal function.

What is the cloudy urine caused by?

A

Propofol Infusion Syndrome

Uric acid crystallization (no alteration to renal function)

123
Q

What is Propofol Infusion Syndrome?

A

aka PRIS
High dose infusions of >75 μg/kg/min for >24 hours.

124
Q

What can PRIS cause?

A

Severe, refractory, and fatal bradycardia in children

125
Q

What are the S/S’s of PRIS?

A

Lactic acidosis
Bradycardia
Rhabdomyolysis
Green urine

126
Q

Is PRIS reversible?

A

In the early stages

127
Q

What happens if someone with PRIS is in cardiogenic shock?

A

Treatment: Extracorporeal membrane oxygenation (ECMO)

128
Q

What are propofols effects on the following:

Intraocular pressure
Platelet aggregation
Myoclonus

A

Decreased
Inhibition
Prolonged

129
Q

T/F Propofol is prone to abuse and misuse.

A

True

130
Q

T/F Propofol is prone to allergic reactions.

A

True

Anesthesia Pharmacology Review (4 decks)

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