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Anesthesia Pharmacology > Induction: Barbiturates and Propofol Test 2 > Flashcards

Induction: Barbiturates and Propofol Test 2 Flashcards

1
Q

A drug that induces a state of calm or sleep.

A

Sedative

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2
Q

A drug that induces hypnosis or sleep.

A

Hypnotic

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3
Q

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

A

Anxiolytic

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4
Q

A drug that reversibly depresses the activity of the CNS.

A

Sedative-Hypnotics

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5
Q

State of drug-induced unconsciousness.

A

General Anesthesia

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6
Q

What is MAC?

A

Monitored Anesthesia Care- administration of a combination of sedatives and analgesics to induce a depressed level of consciousness, allowing patients to tolerate unpleasant procedures and enabling clinicians to perform procedures effectively.

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7
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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8
Q

What makes up the Vessel-rich group?

A

Brain
Heart
Kidney
Liver

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9
Q

What makes up the Muscle group?

A

Skeletal muscle
Skin

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10
Q

What makes up the Vessel-poor group?

A

Bone
Tendon
Cartilage

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11
Q

What are the 5 components of General Anesthesia?

A

Hypnosis
Analgesia
Muscle Relaxation
Sympatholysis (hemodynamic stability)
Amnesia

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12
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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13
Q

What stage can cause death?

A

Stage 4

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14
Q

What stage consist 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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15
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

Still open their eyes on command, breath, have protective reflexes

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16
Q

What are the 3 lower airway protective reflexes?

A

Coughing
Gagging
Swallowing

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17
Q

What is the upper airway reflex?

A

Sneezing

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18
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.
Responses are exagerrated; this stage is passed rapidly due to anesthetic agents

If you stimulating and they respond crazy, stop & give more sedation!

Kids sometimes go through this stage twice

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19
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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20
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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21
Q

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

A

Patient is about to follow commands

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22
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.

W/ diethyl ether, people stayed in stage 2 for a long time

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23
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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24
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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25
Q

What is the MOA of Barbituates?

A

Potentiates GABA-A channel activity; directly mimics GABA.

Acts on glutamate, adenosine, and neuronal nicotinic acetylcholine receptors

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26
Q

Barbiturates are a cerebral _____________.

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

A

Cerebral vasoconstrictor

CBF decreases
CMRO2 decreases by 55%

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27
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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28
Q

Do barbiturates cause analgesic effects?

A

No Analgesia

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29
Q

What is the onset time of barbiturates?

Barbiturates have a rapid redistribution at 5 minutes __________ of the total dose in the blood.

How much of the total dose will be in the blood after 30 minutes?

A

30 seconds

50%

10%

Rapid distribution from brain to other tissues

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30
Q

What will result from a prolonged infusion time of barbiturates?

A

Lengthy context-sensitive half-time

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31
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.

Stays in the fat for long bc it is lipid soluble

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32
Q

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

A

fat and lean tissues

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33
Q

What is the site of the initial redistribution for barbiturates?

Equilibrium at __________ minutes to plasma.

When will perfusion decrease?

Who has mass decrease?

A

Skeletal muscles

15 minutes

Perfusion decrease d/t shock

The elderly will have a mass decrease

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34
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.

Barbs are dosed on lean body weight

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35
Q

How are Barbituates metabolized?

How are they excreted?

Elimination half-time consideration for pediatrics?

A

Hepatocytes 99%

Renal
Pediatrics have a half-time (higher metabolism)

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36
Q

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 goes the VRG and crosses the BBB, that is when the drug will affect mentation.

Having drug bound to albumin=inactive

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37
Q

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

A

more lipid soluble and favors acidosis

Wants to stay in muscle and fat

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38
Q

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

A

less lipid soluble and alkalosis favors

ionized= more water soluble and inactive

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39
Q

What are previous uses of barbiturates?

A

preanesthetic; not used anymore d/t hangover effects

Grand mal seizures (now uses benzos)

Rectal administration with uncooperative/young patients

Increased ICP, cerebral ischemia

Induction

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40
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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41
Q

What are examples of oxybarbiturates?

A

Methohexital
Phenobarbital
Pentobarbital

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42
Q

What are examples of thiobarbiturates?

A

Thiopental
Thiamylal

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43
Q

What is the dose of Thiopental (sodium pentothal)

A

Dose: 4mg/kg IV

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44
Q

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

Because of this, what are the anesthetic considerations for this medication?

A

10% remains in the brain (rapid redistribution)

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

45
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

46
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

47
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

48
Q

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

A

Blood-gas coefficient

49
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.

50
Q

Methohexital has a lower lipid solubility than ___________.

A

Pentothal

51
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% (methohexital)
61% (pentothal)

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

we want the non ionized form so it goes straight to the brain and doesnt get bound to anything

52
Q

What are the excitatory phenomenon with methohexital?

A

Myoclonus and Hiccups

myoclonus- direct involuntary muscle movement; not a seizure

53
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)

continuous infusion- post op seizure activity 1 out of 3 patients!

54
Q

Methohexital can induce seizures in patients undergoing ________________.

A

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

55
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

as compared to etomidate

ECT: induce seizure in brains then shock them to induce euphoria and reduce depression!

56
Q

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

A

CV effects of barbiturates (5mg/kg of thiopental)
SBP: Transient 10-20 mmHg decrease
HR: 15 to 20 bpm increase

57
Q

Barbituaries will diminish baroreceptor response in what patients?

A

hypovolemic, CHF, beta blockade

58
Q

Barbiturates will cause __________ release.

A

Histamine

have epinephrine ready

usually asymptomatic

thiopental will acuse anaphylactoid resposne with previous experience

59
Q

What are the side effects of ventilation with barbiturates?

A

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

depressed or apneic

60
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

61
Q

How do you return to spontaneous ventilation with barbiturates?

A

Slow frequency or decrease tidal volume.

in order to get that CO2 up to get them breathing

62
Q

What is the side effect of barbiturates through intra-arterial injection?

Treatment?

A

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

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

63
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

64
Q

2 to 7 days of barbiturate infusion will _________ metabolism of anticoagulation, phenytoin, TCAs, digoxin, corticosteroids, bile salts, and vit K. May persist for 30 days.

Barbituates will cause a modest transient decrease in ________ and _________.

A

accelerate metabolism
due to induction of enzyme CYP450
(more frequent dosing of those drugs will be required)

Renal blood flow and Glomerular filtration rate

make sure BP is normal to increase renal perfusion!

65
Q

Propofol is a ____________ agonist.

A

Gamma Aminobutyric Acid (GABA) agonist

66
Q

What is the dose of propofol for induction?

What is the dose of propofol for conscious sedation?

What is the dose of propofol for maintenance?

Rapid injection (<15 secs) will produce unconsciousness within ________ seconds.

A

Induction: 1.5 to 2.5mg/kg IV

Conscious sedation: 25 to 100 µg/kg/min

Maintenance: 100 to 300 µg/kg/min

30 seconds

67
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)

68
Q

Propofol is
_________% soybean oil

_________% glycerol

_________% purified egg phosphatide (lecithin)

A

Propofol is
10% soybean oil
2.25% glycerol
1.2% purified egg phosphatide (lecithin)

Lecithin is part of the EGG YOLK

69
Q

Disadvantages of propofol:
Supports ________ growth
Causes increased plasma ___________ concentrations (prolonged use)
________ on injection

A

Disadvantages of propofol:
Supports bacteria growth
Causes increased plasma triglyceride concentrations (prolonged use)
Pain on injection (give lidocaine IV before)

70
Q

What are the commercial preparations for propofol?

A

Ampofol (low lipid emulsions with no preservatives, higher incidence of pain on injection)

Aquavan (prodrug that eliminates pain on injection, byproduct will produce pain, larger Vd, higher potency)

Nonlipid with Cyclodextrins (clinical trials)

71
Q

Propofol is a relative modulator of ______________ receptors.

A

GABA-A

72
Q

GABA is the principal inhibitory NT in the ________.
GABA-A receptor activation will increase transmembrane conductance of _________.

Causes what to the postsynaptic cell membrane

A

Brain

Chloride
hyperpolarization of the postsynaptic cell membrane and functional inhibition of the post-synaptic neuron, no transmission of impulse

73
Q

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

A

Spinal cord depression

74
Q

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

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

A

Lungs

Cytochrome P450

75
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

76
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

77
Q

Propofol
Elimination Half Time:
Vd:
Clearance:
SBP trend:
HR trend:

A

Propofol
Elimination Half Time: 0.5-1.5 hrs
Vd: 3.5-4.5 L/kg
Clearance: 30-60 mL/kg/min
SBP trend: Decreased
HR trend: Decreased

78
Q

Etomidate
Elimination Half Time:
Vd:
Clearance:
SBP trend:
HR trend:

A

Etomidate
Elimination Half Time: 2-5 hrs
Vd: 2.2-4.5 L/kg
Clearance: 10-20 mL/kg/min
SBP trend: No change to decrease
HR trend: No change

79
Q

Ketamine
Elimination Half Time:
Vd:
Clearance:
SBP trend:
HR trend:

A

Ketamine
Elimination Half Time: 2-3 hrs
Vd: 2.5-3.5 L/kg
Clearance: 16-18 mL/kg/min
SBP trend: Increase
HR trend: Increase

80
Q

Propofol awakening times with cirrhosis of the liver?

A

Similar awakening time with alcoholic and normal patients.

81
Q

Will renal dysfunction affect propofol clearance?

A

No influence on propofol clearance.

82
Q

Concerns about propofol with pregnancy?

A

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

83
Q

What are the clinical uses of propofol?

A
  1. Induction DOC
  2. Continuous IV infusion (by itself or with other anesthetics, TIVA)
84
Q

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

A

2%
(20 mg/mL)

85
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

86
Q

Propofol dose consideration for the elderly?

A

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

87
Q

Plasma levels of propofol
Unconscious on induction:
Awakening:

A

Plasma levels of propofol
Unconscious on induction: 2 to 6 μg/mL
Awakening: 1.0 to 1.5 μg/mL

88
Q

With intravenous sedation of propofol:
_________ analgesic and amnestic effects.
Prompt recovery without _______________.
Low incidence of postop ____________.
Anti-convulsant properties.
For TIVA, ________ or __________ used as adjuncts.

A

With intravenous sedation of propofol:
Minimal analgesic and amnestic effects.
Prompt recovery without residual sedation.
Low incidence of postop PONV
Anti-convulsant properties.
Midazolam or Opioid used as adjuncts.

89
Q

Propofol is the agent of choice in brief _______ procedures.

A

Gi endoscopy

90
Q

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

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

A

Zofran

Propofol depresses the subcortical pathways and has a direct depressant effect on the vomiting center.

91
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

92
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.

effects associated w neuraxial opoids or choletestasis

93
Q

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

A

1 mg/kg IV

94
Q

Other benefits of propofol include:
Propofol as a bronchodilator
_________ at low doses
Potent ________
Does not trigger _______

A

Other benefits of propofol include:
Propofol as a bronchodilator
Analgesia at low doses
Potent antioxidant
Does not trigger MH

95
Q

Propofol will decrease __________, __________, and ________.
Autoregulation related to CBF and PaCO2 is ________.

A

Propofol will decrease CMRO2, CBF, and ICP
Autoregulation related to CBF and PaCO2 is maintained

96
Q

Large doses of propofol may __________ Cerebral perfusion pressure. Need to support MAP.

CPP = MAP - ICP

A

decrease

97
Q

EEG changes from propofol is similar to ________.

A

Thiopental

98
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.

99
Q

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

A

Seizures

100
Q

Compare SBP of propofol and thiopental.

A

The decrease in SBP in propofol is higher than in thiopental d/t inhibition of the SNS, vascular smooth muscle relaxation, and decrease SVR…also decreases the level of intracellular calcium

101
Q

What are the CV side effects if propofol is given to someone with hypovolemia, elderly, LV compromised.

A

Exaggerated (might consider etomidate instead)

102
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.

103
Q

Pulmonary side effects of propofol.
Dose-dependent ventilation depression will cause _______.
__________ effect with opioids.
__________ hypoxic pulmonary vasoconstriction response.
____________ counteracts the ventilatory depressant effects.

A

Pulmonary side effects of propofol.
Dose-dependent ventilation depression will cause Apnea.
Synergistic effect with opioids.
Intact hypoxic pulmonary vasoconstriction response.
Painful surgical stimulation counteracts the ventilatory depressant effects.

104
Q

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

A

Normal

105
Q

Prolong infusion can cause _________ injury.

A

Hepatocellular

106
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 alternation to renal function)

107
Q

What is the cause of propofol infusion syndrome?

What will this cause?

Signs/Sx?

Reversible?

A

High dose infusion, greater than 75 μg/kg/min for 24 hours.

Cause severe, refractory, and fatal bradycardia in children

Symptoms: Lactic acidosis, bradycardia, rhabdomyolysis, green urine

Reversible in the early stages

108
Q

What happens if someone with PRIS is in cardiogenic shock?

A

Treatment: Extracorporeal membrane oxygenation (ECMO)

109
Q

Propofol side effects on other organs:
______ Intraocular pressure.
Inhibits ____________.
Allergic Reactions
Prolonged __________
Abuse and Misuse

A

Propofol side effects on other organs:
Decrease Intraocular pressure.
Inhibits platelet aggregation
Allergic Reactions
Prolonged myoclonus
Abuse and Misuse

Anesthesia Pharmacology (20 decks)

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