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Anesthesia Pharm (Spring '24) - A > Induction Drugs (Barbs & Propofol) (Exam II) > Flashcards

Induction Drugs (Barbs & Propofol) (Exam II) Flashcards

1
Q

What organs utilize the most blood supply?
What organs utilize the least?
What organs are in between these two groups?

A
  • Vessel-rich group = 75% CP (brain, heart, liver, kidneys)
  • Skeletal muscles & skin = 18% CO
  • Fat = 5% CO
  • Bone, tendons, & cartilage = 2% CO
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2
Q

What are the one-word (ish) summaries of the four stages of anesthesia?

A
  1. Analgesia
  2. Delirium
  3. Surgical Anesthesia
  4. Medullary paralysis (death)
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3
Q

What reflexes are we suppressing during stage 1 anesthesia?
If stage 1 anesthesia is maintained, what is it called?

A
  • Coughing, swallowing, and gagging reflexes (lower airway reflexes)
  • Conscious sedation
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4
Q

During induction, when would one most likely see laryngospasm?

A
  • Stage 2
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5
Q

During emergence, when would one most likely need to be re-intubated?

A
  • Stage 2
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6
Q

What is the mechanism of action of barbiturates?

A
  • Direct mimic of GABA causing Cl⁻ influx & cellular hyperpolarization.
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7
Q

What do barbiturates do to CBF & CMRO₂ ?
How is this accomplished?

A
  • ↓ CBF & ↓ CMRO₂ (by 55%) via cerebral vasoconstriction
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8
Q

What drug class is represented by the figure below? How do you know this?

A
  • Barbiturates
  • Rapid redistribution & lengthy context-sensitive half-time (noted by fat build-up over time)
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9
Q

Where is the site of initial redistribution for barbiturates?
When is equilibrium between plasma concentrations & muscle concentrations reached?

A
  • Skeletal muscles
  • 15 min
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10
Q

Where is the main reservoir for barbiturates?
What does this mean clinically?

A
  • Adipose tissue
  • Dose on lean body weight and note cumulative effects of barbiturates.
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11
Q

What is the metabolism and excretion of barbiturates?

A
  • Hepatic metabolism; Renal excretion
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12
Q

How protein bound (in a percentage) are barbiturates?

A
  • 70 - 85% protein bound
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13
Q

What are the characteristics of a non-ionized barbiturate?

A
  • Lipophillic
  • Acidotic environment is favored.
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14
Q

What are the characteristics of an ionized barbiturate?

A
  • Lipophobic
  • Alkalotic-favored
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15
Q

Why might barbiturates be considered cerebro-protective?

A
  • Barbs = ↓CBF & ↓CMRO₂
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16
Q

Regarding barbiturates, are S-isomers or R-isomers more potent?
Which is used clinically?

A
  • S-isomer barbiturates are more potent
  • Trick question. Racemic mixtures are only ones used.
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17
Q

How would one differentiate thiobarbiturates vs oxybarbiturates?

A
  • Thiobarbiturates: thiopental, thiamylal.
  • Oxybarbiturates: methohexital, phenobarbital, pentobarbital.
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18
Q

What is the dose for Thiopental?
How much is in the brain 30 minutes post-administration? Why?

A
  • 4mg/kg iV
  • 10% in the braine after admin. Rapid redistribution to skeletal muscles occurs.
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19
Q

What is the fat/blood partition coefficient of thiopental?
What does this mean?

A
  • 11
  • Dosing needs to be calculated on Ideal Body Weight.
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20
Q

What does a partition coefficient describe?

A
  • Distribution of a drug between two substances that have the same temp, pressure, and volume.
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21
Q

What is the blood-gas coefficient?

A
  • Number that describes the distribution of an anesthetic between blood and gas at the same partial pressure.
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22
Q

What would a high blood-gas coefficient indicate?

A
  • Slower Induction time

Essentially, drug is taken up into the blood and wants to stay in the blood rather than going to tissues like the brain.

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23
Q

Which is more lipid soluble, thiopental or methohexital?

A
  • Thiopental (Sodium Pentothal)
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24
Q

At a normal pH _____% of methohexital is non-ionized.

At a normal pH ____% of sodium pentothal is non-ionized.

What does this mean in regards to induction for comparing these drugs?

A
  • 76%
  • 61%
  • Methohexital for induction has a faster metabolism and recovery due to its increased lipid-solubility.
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25
Q

Which barbiturate causes excitatory symptoms like myoclonus and hiccups?

A

Methohexital

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26
Q

How would methohexital infusions differ from induction?

A

Very lipid-soluble so:

  • Drug persists from infusion but clears quickly from induction.
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27
Q

What is the IV methohexital dose?
What if it needs to be given rectally?

A
  • 1.5 mg/kg IV
  • 20 - 30 mg/kg PR
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28
Q

What is the seizure profile of methohexital?

A

Can induce seizures but is better than etomidate or when used with ECT.

  1. Continuous infusions induce post-op seizures in ⅓ of patients.
  2. Seizures are induced in patients undergoing temporal lobe resection.
  3. Seizure duration reduced 35-45% in ECT patients vs etomidate.
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29
Q

What cardiovascular side effects would occur with thiopental administration in a normovolemic patient?

A
  • Transient sBP decrease of 10-20mmHg
  • Transient HR increase of 15-20 bpm
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30
Q

What patient conditions could result in poor baroreceptor response after barbiturate administration?

A
  • Hypovolemia, CHF, & β-blockade
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31
Q

Thiopental can have a __________ type response due to __________ release coupled with previous exposure to the drug.

A

anaphylactic ; histamine

32
Q

What are the respiratory effects of barbiturates?

A

Dose-dependent medullary & pontine respiratory depression.

(Less sensitivity to CO₂ levels).

33
Q

What would occur with accidental arterial administration of a barbiturate?
What is the treatment?

A
  • Immediate, limb-threatening vasoconstriction.
  • Lidocaine or papaverine injection as well as any other vasodilatory method.
34
Q

When would CYP450 enzyme induction be seen with a barbiturate infusion?
How long could it last?

A
  • 2-7 days post-infusion
  • CYP450 induction could last up to 30 days.
35
Q

What renal effects would one expect to see after barbiturate administration?

A
  • Transient ↓RBF and ↓GFR
36
Q

For Propofol, what are the doses for:
1. Induction
2. Maintenance
3. Conscious sedation

A
  1. Induction = 1.5 - 2.5 mg/kg IV
  2. Maintenance = 100 - 300 μg/kg/min
  3. Conscious sedation = 25 - 100 μg/kg/min
37
Q

What is the most common concentration of a 1% solution?

A
  • 10mg/mL
38
Q

What are the inactive ingredients in propofol? Why is one particularly important?

A
  • 1.2% Lecithin (from egg yolks) can cause anaphylaxis with egg allergies.
  • 2.25% glycerol
  • 10% soybean oil
39
Q

What are the disadvantages of propofol’s inactive ingredient composition?

A
  • ↑ bacterial growth
  • ↑ plasma triglycerides with prolonged infusions
  • Pain on injection
40
Q

Differentiate Ampofol and Aquavan.

A
  • Ampofol - low-lipid, no preservative that burns on injection more often.
  • Aquavan - prodrug with less injection pain but causes dysesthesias. Slower onset, larger Vd, and high potency.
41
Q

What is the mechanism of action of propofol?

A
  • GABA receptor modulator that increases Cl⁻ conductance.
42
Q

How does propofol cause immobility through spinal cord-depression?

A
  • Trick question. Immobility from propofol is not from drug-induced spinal cord depression.
43
Q

What are the clearance characteristics of propofol?

A

The clearance of propofol is primarily through hepatic metabolism, with minor contributions from renal clearance and pulmonary elimination.

44
Q

What metabolizes propofol?

A
  • CYP450 and UGT1A9
45
Q

What is the E ½ time of propofol?

A
  • 30 - 90 minutes
46
Q

What is the context-sensitive half-time of propofol? Is this a relatively low or high context half-time?

A
  • 40 minutes (for an 8 hours infusion)
  • Low CS ½ time.
47
Q

What are the following characteristics of propofol:
1. Elimination ½ time.
2. Volume of distribution
3. Clearance (mL/kg/min)

A
  1. E ½ time = 30 - 90 minutes
  2. Vd = 3.5 - 4.5
  3. Clearance = 30 - 60 mL/kg/min
48
Q

Differentiate blood pressure and heart rate changes that occur with propofol vs thiopental.

A
  • Propofol: ↓BP & ↓HR
  • Thiopental: ↓BP & ↑HR
49
Q

Does propofol cross the placenta? What are the consequences of this?

A
  • Yes but is rapidly cleared from neonatal circulation.
50
Q

Do cirrhosis and renal dysfunction have significant effects on propofol metabolism?

A

No

(Induction drugs 1, slide 43)

51
Q

What drug is the induction drug of choice?

A

Propofol

52
Q

What is the induction dose of propofol in adults? Children?

A
  • Adults: 1.5-2.5 mg/kg IV
  • Pediatrics: higher doses due to larger central volume and clearance rate.
53
Q

What is the induction dose of propofol in the elderly?

A
  • 1 mg/kg IV (25 - 50% lower than regular adult)
54
Q

What plasma propofol levels would correlate with unconsciousness?
What about awakening?

A
  • Unconscious: 2 - 6 μg/mL
  • Awake: 1 - 1.5 μg/mL
55
Q

What is the conscious sedation dose of propofol?

A
  • 25 - 100 μg/kg/min
56
Q

What are the characteristics of propofol in the context of conscious sedation?

A
  • Minimal analgesia but has anti-convulsive and amnestic properties.
  • Prompt recovery w/ low residual sedation
  • ↓ risk of PONV
  • Midazolam or opioids as adjuncts.
57
Q

What are the anti-emetic properties of propofol?
Why is this thought to occur?

A
  • Very anti-emetic (more effective than ondansetron)
  • Direct depressant of vomiting center
58
Q

What is the sub-hypnotic dosing for propofol?

A
  • 10 - 15 mg IV, followed by 10 mcg/kg/min
59
Q

What is the anti-pruritic dosing of propofol?

A
  • 10 mg IV
60
Q

What is the anti-convulsant dosing of propofol?

A

1mg/kg IV

61
Q

What are “other” category benefits of propofol?

A
  • Bronchodilation
  • Anti-emetic
  • Anti-pruritic
  • Anti-convulsant
  • Low dose analgesia
  • Antioxidant
  • Does not trigger MH
62
Q

What are propofol’s effects on CMRO₂, CBF, and ICP?

A
  • ↓ CMRO₂, CBF, and ICP
63
Q

Large doses of propofol may ______ cerebral perfusion pressure.

A

decrease

64
Q

Though propofol will not produce seizures, it will produce _______.

A

myoclonus

65
Q

Between thiopental, propofol, and isoflurane, which is the least EEG suppressive?

A
  • Propofol
66
Q

Which would decrease blood pressure more, thiopental or propofol?

A

Propofol

67
Q

What is the mechanism for propofol-induced hypotension?
What conditions will exaggerate this effect?

A
  • SNS inhibition causing ↓SVR and ↓ ICF Ca⁺⁺.
  • Hypovolemia, elderly, and LV compromise
68
Q

How is propofol-induced hypotension from induction usually counteracted?

A
  • Intubation (from laryngeal stimulation).
69
Q

Why is bradycardia seen with propofol?
What would occur with propofol overdose?

A
  • ↓SNS response & baroreceptor reflex
    depression.
  • Profound bradycardia & eventual asystole.
70
Q

What are the pulmonary effects of propofol?
How does this change with opioids?

A
  • Dose-dependent depression of respiratory drive.
  • Synergistic resp depression with opioids
71
Q

What severe condition(s) can occur with prolonged propofol infusions?

A
  • Hepatocellular injury or Propofol Infusion Syndrome.
72
Q

What is Propofol Infusion Syndrome?

A
  • Metabolic acidosis thought to occur from poisoning of electron transport chain and impaired oxidation of fatty acids.
73
Q

What relatively benign condition(s) can occur from prolonged propofol infusions?
Why does this happen?

A

Green and cloudy urine from phenols and uric acid crystals.

Neither alters renal function.

74
Q

What sort of infusion dosing can result in propofol infusion syndrome?

A
  • > 75 μg/kg/min for longer than 24 hours
75
Q

What is the worst side effect in children who have propofol infusion syndrome?

A
  • Severe, refractory, fatal bradycardia
76
Q

What are the symptoms of propofol infusion syndrome?
How is propofol infusion syndrome diagnosed?

A
  • Urine changes, lactic acidosis, brady-dysrhythmias, and rhabdomyolysis.
  • ABG & serum lactate concentrations.
77
Q

What are the “other” organ system effects of propofol?

A
  • Injection pain (lido before)
  • ↓ IOP
  • Plt aggregation inhibition
  • Allergic reactions (lecithin)
  • Prolonged myoclonus
  • Abuse/misuse

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

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