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Anesthesia Pharm (Spring '24) - C > Lecture 5 Induction: Barbiturates and Propofol Test 2 > Flashcards

Lecture 5 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 sedative or analgesic, allowing patients to tolerate unpleasant procedures and enabling clinicians to perform procedures effectively.

AKA Procedure Sedation/ Conscious Sedation

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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

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16
Q

What are the 3 lower airway 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.

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19
Q

What is the response to stimulation in Stage 2 like?

A

Exaggerated and violent

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20
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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21
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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22
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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23
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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24
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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25
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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26
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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27
Q

Barbiturates are a cerebral _____________.

What will be the effect on CBF?
What will be the effect on CMRO2?
What is the level of analgesia that it provides?

A

Cerebral vasoconstrictor

CBF decreases
CMRO2 decreases by 55%
Provides no analgesia

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28
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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29
Q

Do barbiturates cause analgesic effects?

A

No Analgesia

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30
Q

What is the onset time of barbiturates?

Barbiturates have a rapid redistribution from brain to other tissues. 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%

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31
Q

What will result from a prolonged infusion time of barbiturates?

A

Lengthy context-sensitive half-time

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32
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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33
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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34
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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35
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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36
Q

Usually, barbituates are dosed on ________ body weight.

A

lean

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37
Q

How are Barbituates metabolized?

How are they excreted?

Elimination half-time consideration for pediatrics?

A

Hepatocytes 99%

Renal

Shorter half-time (higher metabolism)

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38
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.

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39
Q

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

A

more lipid soluble and acid favors

Wants to stay in muscle and fat

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40
Q

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

A

less lipid soluble and alkalosis favors

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41
Q

What are previous uses of barbiturates?

A

Premedication - Not used anymore (hangover)

Grand mal seizures (now uses benzos)

Rectal administration with uncooperative/young patients

Increased ICP, cerebral protection

Induction

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42
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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43
Q

What are examples of oxybarbiturates?

A

Methohexital
Phenobarbital
Pentobarbital

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44
Q

What are examples of thiobarbiturates?

A

Thiopental
Thiamylal

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45
Q

What is the dose of Thiopental (sodium pentothal)

A

Dose: 4mg/kg IV

46
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.

47
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

48
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

49
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

ChatGPT: The partition coefficient in pharmacology measures how well a drug dissolves in fats compared to water. It shows a drug’s ability to cross cell membranes, affecting its absorption and distribution in the body. A higher value means the drug is more fat-soluble and can easily move through lipid-rich areas.

50
Q

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

A

Blood-gas coefficient

51
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.

52
Q

Methohexital has a lower lipid solubility than ___________.

A

Thiopental (Sodium Pentothal®️)

53
Q

At a normal pH, _________% of methohexital is non-ionized. What percent of Thiopental (sodium pentothal) is non-ionized?

What is the metabolism and recovery of methohexital?

A

At a normal pH…

76% (methohexital) is non-ionized
61% (pentothal) is non-ionized

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

54
Q

What are the excitatory phenomenon with methohexital?

A

Myoclonus and Hiccups

55
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)

56
Q

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

A

Seizure

57
Q

Methohexital can induce seizures in patients undergoing ________________.

A

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

58
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

59
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

60
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

61
Q

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

A

Histamine

have epinephrine ready

62
Q

What are the side effects of ventilation with barbiturates?

A

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

63
Q

What is the relationship between Barbiturates and sensitivity to CO2 and what will it cause?

A

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

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

64
Q

How do you return to spontaneous ventilation with barbiturates?

A

Slow frequency or decrease tidal volume.

65
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)

66
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

67
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

(more frequent dosing will be required)

Renal blood flow and Glomerular filtration rate

68
Q

Propofol is a ____________ agonist.

A

Gamma Aminobutyric Acid (GABA) agonist

69
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

70
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)

71
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

72
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)

73
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)

74
Q

Propofol is a relative modulator of ______________ receptors.

A

GABA-A

75
Q

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

A

Brain

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

76
Q

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

A

Spinal cord depression

77
Q

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

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

A

Lungs

Cytochrome P450

78
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

79
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

80
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

81
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

82
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

83
Q

Propofol awakening times with cirrhosis of the liver?

A

Similar awakening time with alcoholic and normal patients.

84
Q

Will renal dysfunction affect propofol clearance?

A

No influence on propofol clearance.

85
Q

Concerns about propofol with pregnancy?

A

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

86
Q

What are the clinical uses of propofol?

A
  1. Induction DOC
  2. Continuous IV infusion (by itself or with other anesthetics, TIVA[Total IV Anesthesia])
87
Q

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

A

2%
(20 mg/mL)

88
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

89
Q

Propofol dose consideration for the elderly?

A

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

90
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

91
Q

With intravenous sedation of propofol:
_________ analgesic and amnestic effects.
Prompt recovery without _______________.
Low incidence of postop ____________.
Anti-convulsant properties.
________ 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.

92
Q

Propofol is the agent of choice in brief _______ procedures.

A

Gi endoscopy

93
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.

94
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

95
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.

96
Q

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

A

1 mg/kg IV

97
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

98
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

99
Q

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

CPP = MAP - ICP

A

decrease

100
Q

EEG changes from propofol is similar to ________.

A

Thiopental

101
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.

102
Q

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

A

Seizures

103
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

104
Q

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

A

Exaggerated (might consider etomidate instead)

105
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.
106
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.

107
Q

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

A

Normal

108
Q

Prolong infusion can cause _________ injury.

A

Hepatocellular

109
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)

110
Q

What is the cause of PRIS?

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

111
Q

What happens if someone with PRIS is in cardiogenic shock?

A

Treatment: Extracorporeal membrane oxygenation (ECMO)

112
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.
- Pain on injection (<10% of patients)
- Inhibits platelet aggregation
- Allergic Reactions
- Prolonged myoclonus
- Abuse and Misuse

Anesthesia Pharm (Spring '24) - C (20 decks)

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