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KM (Spring 2024) Anesthesia Pharm ** > *Induction Drugs (Barbs & Propofol) (Exam II) > Flashcards

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

1
Q

What is the 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?

A

Monitored Anesthesia Care (MAC)
Procedural Sedation/ Conscious Sedation

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2
Q

What organs utilize the most blood supply?

A
  • Vessel-rich group = 75% CP (brain, heart, liver, kidneys)

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3
Q

What organs are in between Vessel-rich and Vessel-poor groups?

A
  • Skeletal muscles & skin = 18% CO
  • Fat = 5% CO

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4
Q

What organs utilize the least?

A

Bone, tendons, & cartilage = 2% CO

S7

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5
Q

What are the components of General Anesthesia?

A
  1. Hypnosis
  2. Analgesia
  3. Muscle Relaxation
  4. Sympatholysis
  5. Amnesia

S8

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6
Q

What are the four stages of anesthesia?

A

Stage 1- Analgesia
Stage 2 -Delirium
Stage 3 - Surgical Anesthesia
Stage 4 - Medullary paralysis (death)

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7
Q

What is Stage 1 and what is the pt. able to do?

A
  • initiation of anesthesia to loss of conscsiousness
  • lightest level of anesthesia

Patient able to:
-open their eyes on command
-breathe normally
-maintain protective reflexes
-tolerate mild stimuli

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8
Q

What reflexes are we suppressing during stage 1 anesthesia?

A

Coughing, swallowing, and gagging reflexes (lower airway reflexes)

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9
Q

What is Stage 2 and what is it characterized?

A

loss of consciousness to onset of automatic (voluntary) rhythmicity

characterized by excitement (undesired CV instability excitation, dysconjugate ocular movements, laryngospasm, and emesis)

Passed rapidly due to response to stimulation is exaggerated and violent

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10
Q

During induction, when would one most likely see laryngospasm?

A
  • Stage 2

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11
Q

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

A
  • Stage 2

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12
Q

What is Stage 3 and its components?

A

Depression in all elements of nervous system function
and
Absence of response to surgical incision

Components:
* hypnosis
* analgesia
* muscle relaxation
* sympatholysis
* amnesia

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13
Q

What is Stage 4 and its characteristics?

A

with cessation of spontaneous respiration and medullary cardiac reflexes

-may lead to death

characteristics:
-all reflexes are absent
-flaccid paralysis
-hypotension with weak, irregular pulse

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14
Q

Why are Barbituates talked about
(according to Castillo)?

A
  • still used in other countries
  • **GOLD STANDARD as comparison with other drugs **

S17

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15
Q

What is the mechanism of action of barbiturates?

A
  • potentiate GABA -A channel activity
  • Direct mimic of GABA causing Cl⁻ influx & cellular hyperpolarization.

*No analgesia

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16
Q

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

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

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17
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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18
Q

What is the onset of Barbituates and how is the patient affected?

A

Rapid onset of 30 seconds

Rapid awakening due to rapid uptake

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19
Q

Where is the site of initial redistribution for barbiturates?

When is equilibrium between plasma concentrations & muscle concentrations reached?

A
  • Skeletal muscles
  • 15 min
    *mass decreased on elderly

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20
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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21
Q

What is the metabolism and excretion of barbiturates?

A
  • Hepatic metabolism
  • Renal excretion

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22
Q

Elimination 1/2 of Barbituates is shorter for which population

A

Pediatrics

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23
Q

What are Barbiturates bound and how much?

A

70 - 85% protein bound on Albumin

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24
Q

What are the characteristics of a non-ionized barbiturate?

A
  • Lipophillic
  • Acidotic environment is favored.

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25
Q

What are the characteristics of an ionized barbiturate?

A
  • Lipophobic
  • Alkalotic-favored

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26
Q

What were previous uses of Barbituates?

A
  • Premedication
  • treat Grand mal seizures
  • rectal administration with uncooperative/young patients
  • increased ICP
  • cerebral protection
  • induction

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27
Q

Why might barbiturates be considered cerebro-protective?

A

↓CBF & ↓CMRO₂

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28
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.

S24

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29
Q

How would one differentiate thiobarbiturates vs oxybarbiturates?

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

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30
Q

What is the dose for Thiopental?

A

4mg/kg iV

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31
Q

How much is in the brain 30 minutes post-administration? Why?

A

10% in the brain after admin.
Rapid redistribution to skeletal muscles occurs.

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32
Q

What is the Elimination 1/2 time of Thiopental?

A

longer than methoxital

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33
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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34
Q

What is distribution of a drug between two substances that have the same temp, pressure, and volume?

A

partition coefficient

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35
Q

What is the number that describes the distribution of an anesthetic between blood and gas at the same partial pressure?

A

blood-gas coefficient

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36
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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37
Q

Which is more lipid soluble: thiopental or methohexital?

A

Thiopental (Sodium Pentothal)

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38
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% non-ionized Methohexital
  • 61% non-ionized Sodium Pentothal
  • Methohexital for induction has a faster metabolism and recovery due to its increased lipid-solubility.

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39
Q

Which barbiturate causes excitatory symptoms like myoclonus and hiccups?

A

Methohexital

S29

40
Q

How would methohexital infusions differ from induction?

A

Very lipid-soluble so:

  • Drug persists from infusion but clears quickly from induction.

?

41
Q

What is the IV methohexital dose?

A

1.5 mg/kg IV

S30

42
Q

What is per rectum dose of Methohexital?

A

20 - 30 mg/kg PR

S30

43
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.

S30

44
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

S31

45
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

S31

46
Q

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

A

anaphylactic due to histamine release

S31

47
Q

What are the respiratory effects of barbiturates?

A
  • Dose-dependent medullary & pontine respiratory depression.

= Less sensitivity to CO₂ levels
*pt. will need more CO₂ for voluntary breathing
(slow frequency of RR and decreased Vt)

S33

48
Q

How do you return to spontaneous ventilation with barbiturates?

A

Slow frequency or decrease tidal volume.

Slide 33

49
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.

S34

50
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

Slide 35

51
Q

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

A

accelerate metabolism

(more frequent dosing will be required)

Slide 35

52
Q

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

A

Transient ↓RBF and ↓GFR

S35

53
Q

What is the Induction dose of Propofol

A

1.5 - 2.5 mg/kg IV

S37

54
Q

What is the conscious sedation dose of Propofol?

A

25 - 100 µg/kg/min

S37

55
Q

What is the maintenance dose of Propofol?

A

100 to 300 µg/kg/min

S37

56
Q

What does rapid injection (<15 seconds) of Propofol produce?

A

unconsciousness within 30 seconds

S37

57
Q

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

A
  • 10mg/mL

S39

58
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

S39

59
Q

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

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

S39

60
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
- high potency.

S40

61
Q

What is the mechanism of action of propofol?

A

GABA-A receptor modulator that increases Cl⁻ conductance.

S41

62
Q

How does propofol cause immobility through spinal cord-depression?

A
  • Trick question. Immobility from propofol is not from drug-induced spinal cord depression.
63
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.

S 42

64
Q

What is the clearance of Propofol?

A

30 - 60 mL/kg/min

S42 and S44

65
Q

What metabolizes propofol?

A

CYP450 and UGT1A9

S42

66
Q

What is the E ½ time of propofol?

A
  • 30 - 90 minutes

S 42

67
Q

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

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

S42

68
Q

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

A
  • Propofol: ↓BP & ↓HR
  • Thiopental: ↓BP & ↑HR
69
Q

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

A
  • Yes but is rapidly cleared from neonatal circulation.

S45

70
Q

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

A

No

S45

71
Q

What drug is the induction drug of choice?

A

Propofol

S46

72
Q

What is theinduction dose of propofol in adults and children?

A
  • Adults: 1.5-2.5 mg/kg IV
  • Pediatrics:** higher doses** due to larger central volume and clearance rate.
73
Q

What is the induction dose of propofol in the elderly?

A

1 mg/kg IV (25 - 50% lower than regular adult)

S47

74
Q

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

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

S47

75
Q

What is the conscious sedation dose of Propofol?

A

25 - 100 μg/kg/min

76
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.

S47

77
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

S49

78
Q

What is the sub-hypnotic dosing for propofol?

A

10 - 15 mg IV, followed by 10 mcg/kg/min

S49

79
Q

What is the anti-pruritic dosing of propofol?

A

10 mg IV

from Neuraxial opioids or cholestasis

S50

80
Q

What is the anti-convulsant dosing of Propofol?

A

1 mg/kg IV

S50

81
Q

What are “other” category benefits of propofol?

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

S50

82
Q

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

A
  • ↓ CMRO₂, CBF, and ICP

S51

83
Q

Large doses of Propofol may ___________ cerebral perfusion pressure.

A

decrease

S51

84
Q

Though Propofol will not produce seizures, it will produce __________.

A

myoclonus
(involuntary twitching or jerking)

S51

85
Q

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

A

Propofol

S52

86
Q

Which would decrease blood pressure more: thiopental or propofol?

A

Propofol

S53

87
Q

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

A
  • SNS inhibition causing ↓SVR and ↓ ICF Ca⁺⁺
  • exaggerated in Hypovolemia, elderly, and LV compromise

S53

88
Q

How is propofol-induced hypotension from induction usually counteracted?

A
  • Intubation (from laryngeal stimulation).
89
Q

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

A
  • ↓SNS response & baroreceptor reflex
    depression.
  • Profound bradycardia & eventual asystole with overdose

S54

90
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
  • Intact hypoxic pulmonary vasoconstriction response
  • Painful surgical stimulation counteracts the ventilatory depressant effects

S55

91
Q

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

A

Hepatocellular injury or Propofol Infusion Syndrome.

S56

92
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.

S56

93
Q

What is Metabolic acidosis thought to occur from poisoning of electron transport chain and impaired oxidation of fatty acids?

A

Propofol Infusion Syndrome

S57

94
Q

What infusion dosing can result in Propofol Infusion Syndrome?

A

> 75 μg/kg/min for longer than 24 hours

S57

95
Q

What is the worst side effect in children who have Propofol Infusion Syndrome?

A
  • Severe, refractory, fatal bradycardia

S57

96
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

*Reversible in the early stage

S57

97
Q

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

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

S58

KM (Spring 2024) Anesthesia Pharm ** (101 decks)

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