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Anesthesia Pharm (Spring '24) - C > Lecture 3 Sedatives/ Hypnotics Test 1 > Flashcards

Lecture 3 Sedatives/ Hypnotics Test 1 Flashcards

1
Q

A drug that induces calm or sleep is called a _______.

A drug that induces hypnosis is called a _________.

A

Sedative

Hypnotic

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2
Q

Both general anesthesia and sleep share similarities in that both inhibit _________ and ___________.

General anesthesia and sleep also reversibly inhibit the ________.

A

Thalmic
Mid-Brain Reticular Activating System (RAS)

CNS

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3
Q

1 in 10,000 patients will experience this in general anesthesia.

A

Awareness

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4
Q

In 1937, ___________ could be used to measure the effects of anesthesia.

A

EEG

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5
Q

In 1952, the depth of anesthesia correlates with ___________ of ether used.

A

Concentration or MAC

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6
Q

Anesthesia alters ____________ and ______________.

A

Cerebral Blood Flow (CBF)

Cerebral Metabolic Rate of Oxygen (CMRO2)

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7
Q

What was the issue with using EEG machines to measure the depth of general anesthesia?

A

Not practical to use so many leads and the device was large and bulky.

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8
Q

In 1996 the __________ was created using 1500 subjects and 5000 hours of EEG signals. It uses an algorithm and pattern to determine a patient’s depth under general anesthesia.

A

Bispectral Analysis

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9
Q

What was the BIS tested with?

A

Isoflurane/O2
Propofol/ Nitrous
Propofol/ Alfentanil

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10
Q

BIS change correlates to _____________.

What is the exception?

A

Patient movement.
The lower the number, the less movement

Exception: High dose narcotics have less correlation between BIS and movement

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11
Q

No patient with a BIS score less than _________ was conscious.

BIS scores less than ________ show that less than 5% chance of return to consciousness within 50 seconds.

A

58

65

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12
Q

What is the BIS range?

What is the ideal BIS range for someone under general anesthesia?

A

0 to 100

40 to 60

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13
Q

On the BIS monitor, what is the SQI?

EMG?
EEG?
SR?

A

SQI - Signal Quality Index

EMG- Electromyographic, tells you if the patient is about to move

EEG- brain activity

SR- Suppression Ratio, should be 0, how many seconds in the last minute has the EEG been flat.

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14
Q

Are BIS monitors 100% reliable?

A

No, different drugs such as ketamine and epinephrine can give the BIS monitor a falsely high reading despite the patient being adequately sedated.

Very important to look at BIS trends

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15
Q

What are the five main actions of BZDs?

A
  1. Anxiolytics
  2. Sedation
  3. Anterograde Amnesia (this last longer than sedative effects)
  4. Anticonvulsant
  5. Spinal Cord mediated skeletal muscle relaxation (not adequate for surgery)
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16
Q

What were the reasons that BZD replaced barbiturates for preop sedation?

A

Less tolerance was developed with BZD.
BZD had less potential for abuse.
BZD had fewer and less serious S/E.
BZD does not induce hepatic microsomal enzymes.

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17
Q

What are the similarities between BZD and barbituates?

A

Similar structure
Specific pharmacologic antagonist (flumazenil)

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18
Q

What is the most commonly used BZD in the perioperative period? This is also used as a preop med and for conscious sedation.

A

Midazolam (Versed)

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19
Q

Which two BZD have a greater half time than midazolam and more attractive for sedation post-op?

A

Diazepam (Valium)
Lorazepam (Ativan)

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20
Q

What is the MOA of a BZD?

A

The mechanism of action is GABA- mediated.
BZD binds at GABA-A Chloride Inophore receptors. This will enhance the affinity of receptors for GABA, opening chloride channels and inducing hyperpolarization.

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21
Q

Which receptor subunit on GABA is the most abundant?

What effect does it have?

What part of the brain does it affect?

A

Alpha-1

Sedative, Amnestic, Anticonvulsant

Cerebral cortex, Cerebellar cortex, thalamus

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22
Q

What receptor subunit on GABA exhibits anxiolytic and skeletal muscle relaxation?

What part of the brain does it affect?

A

Alpha-2

Hippocampus, amygdala

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23
Q

Name agents or drugs that can have a synergistic effect with BZD.

A

Barbituates
Injected Anesthetics (Propofol)
Inhaled Anesthetics
Etomidate
Alcohol
Opioids
Alpha-2 agonist (Precedex)

All these bind to the Alpha subunit on the GABA receptor

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24
Q

The BZD that we use in anesthesia is highly ______________ and highly (98%)________________.

What does that mean?

A

Lipid Soluble
Protein Bound

This means that BZD will work quickly and go away quickly.

B/c they are lipid soluble, BZD will have a large Vd, just not a large amount because they are highly protein bound

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25
Q

Looking at an EEG, BZD will decrease __________ activity.

Some BZD are unable to produce a _______________ state.

BZD will cause ______________ amnesia.

A

Alpha

Isoelectric state

Anterograde

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26
Q

BZD inhibits _________________. Increasing the risk of bleeding.

A

Platelet aggregating factors

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27
Q

What type of structure does a BZD have that allows rapid metabolism?

A

Imidazole ring

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28
Q

How many more times potent is midazolam compared to diazepam?

A

2-3x, midazolam has a greater affinity for the receptor

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29
Q

What are special considerations to take into account for patients coming off of midazolam-induced sedation?

A

Amnestic effects last longer than sedation, have written instructions ready to go

30
Q

At a pH ___________, midazolam is ___________ with an open ring and protonated.

A

less than 3.5, water-soluble

31
Q

At a pH ___________, midazolam is ___________ with a closed ring and non-protonated.

A

greater than 4, lipid-soluble

32
Q

Is midazolam irritating to the veins?

A

No, midazolam is non-irritating

33
Q

What is the onset time over midazolam?

What is peak effect time?

What is the estimated half-time of midazolam?

A

1-2 minutes

5 minutes

2 hours (doubles for the elderly).

34
Q

What causes the short duration of action for midazolam?

A

Lipid solubility and rapid redistribution

35
Q

What is the volume of distribution for midazolam?

A

1 to 1.5L/kg

36
Q

What metabolizes midazolam?

What does midazolam metabolize into?

A

Cytochrome P-450 enzymes (CYP 3A4)

Active and inactive metabolites
1-hydroxymidazolam (half the activity of the parent)

37
Q

What are drugs that can inhibit P-450 enzymes and decrease BZD metabolism?

A

Cimetidine
Erythromycin
CCB
Antifungal
Fentanyl

38
Q

Clearance of midazolam is _______ faster than lorazepam.

Clearance of midazolam is _________ faster than diazepam.

A

5 times

10 times

39
Q

CMRO2 and CBF effect of midazolam?

Isoelectric EEG with midazolam?

A

Both Decrease

Unable to produce isoelectric effect with midazolam.

40
Q

Midazolam is a potent _____________ (even in status)

A

Anticonvulsant

41
Q

Midazolam preserves __________________ response to CO2.

A

Vasomotor

42
Q

Why is midazolam a great drug to give to neuro patients?

A

Does not increase ICP.

43
Q

List pulmonary effects of midazolam.

A

Dose-dependent and will decrease ventilation and hypoxic drive.
Greater depression with COPD and transient apnea if rapid IV infusion with opioids.
Decrease swallowing reflex.
Decrease upper airway activity.

44
Q

What are the cardiovascular effects of midazolam?
HR:
BP:
SVR:

A

Dose-dependent
HR: Increases
BP: Decreases
SVR: Decreases

Does not inhibit BP/HR response to intubation

45
Q

What is midazolam dosing for sedation in children?

What will be the peak effect time?

A

0.25 to 0.5 mg/kg (syrup)

20-30 minutes

46
Q

What is midazolam dosing for sedation in adults?

What will be the peak effect time?

A

1-5 mg IV

5 minutes

47
Q

What is midazolam dosing for adult induction?

What will be the preceding dose of opioids?

A

0.1-0.2 mg/Kg IV over 30-60 seconds

Facilitated by a preceding dose of opioid (1-3 minutes), 50 to 100 mcg of fentanyl (synergistic effect)

48
Q

It is uncommon to use midazolam for ___________. Instead, supplemented with opioids, propofol, and volatiles.

Midazolam is rarely associated with _____________ or ______________.

A

Maintenance (but decreases the requirement for volatiles)

N/V; emergence excitement (crazy)

49
Q

What is midazolam dosing for post-op sedation?

What are the considerations to take into account for this?

A

1-7 mg/hr IV

-2-3 days max because prolong use will cause T-cell suppression.
-Accumulation of Active metabolites and clearance depends on hepatic metabolism, not redistribution.

50
Q

Diazepam is highly ____________ soluble and has a more prolonged duration of action than midazolam. Rarely used in anesthesia.

A

Lipid

51
Q

What substance is in diazepam that causes irritation and burning to the veins?

A

Propylene glycol

Soybean formulation is less painful

52
Q

What is the onset time for diazepam?

What is the half-time for diazepam?

A

1-5 minutes

20-40 hours (10-20 times longer than versed)

53
Q

What metabolizes diazepam?

What does diazepam metabolize into?

When will patients experience return drowsiness?

A

Cytochrome P-450 enzymes (CYP 3A4)

Activate metabolites as nearly as potent as the parent
Desmethydiazepam and oxazepam

Return drowsiness in 6-8 hours

54
Q

What are CNS effects of diazepam?
CBP:
CMRO2:
Isoelectric EEG:

A

CBP: decrease
CMRO2: decrease
Isoelectric: Can produce an isoelectric effect

55
Q

What is the diazepam dose for an anticonvulsant?

What else can this be used to treat?

A

0.1 mg/kg IV

DTs, status epilepticus, lidocaine toxicity related seizures

56
Q

What are the pulmonary effects of diazepam?

After __________ mg/kg IV, there will be an increase in PaCO2.

What will reverse ventilatory depressant of diazepam?

A

A slight decrease in tidal volume that can be exaggerated with opioids, alcohol, and COPD

0.2 mg/kg

Surgical Stimulation

57
Q

What are the cardiovascular effects of diazepam?
BP:
CO:
SVR:

A

What are the cardiovascular effects of diazepam?
BP: Minimal
CO: Minimal
SVR: Minimal

BP changes with opioids and unchanged with the addition of nitrous

58
Q

What are the neuromuscular effects of diazepam?

A

Decrease muscle tone, decrease tonic effect on spinal neuron

59
Q

What is the dosing of diazepam for induction?

What are the considerations when it comes to dosing for the elderly, patients with liver disease, or the presences of opioids?

A

0.5 - 1.0 mg/kg IV

Decrease dose by 25% to 50%

60
Q

Compared to midazolam and diazepam, ____________ is the most potent sedative and amnestic of the three.

A

Lorazepam

61
Q

Lorazepam is ______________ soluble.

This drug has a __________ onset of action and __________ metabolic clearance when compared to midazolam.

A

Lipid soluble (insoluble in water, will have irritation)

Slower onset and slower metabolic clearance.
(slower entrance to CNS too)

62
Q

What is the IV dose of Ativan?

What is the peak effect time?

What is its half-time?

A

1-4 mg IV

20-30 minutes

14 hours

63
Q

What is different about the metabolism of Ativan compared to versed and valium?

A

Ativan is not entirely dependent on the CYP450 enzyme.

64
Q

Organ system effects of Lorazepam?

A

Similar to other BZD and will be dose dependent.

65
Q

Which drug acts as a competitive antagonist with a high affinity for BZD receptors and reverses all agonist activity of BZDs?

A

Flumazenil (Romazicon)

66
Q

How is Flumazenil metabolized?

What does it metabolize into?

A

The hepatic microsomal enzyme (CPY P450, CYP 3A4)

Inactive metabolites.

67
Q

What is the inital dosing of Flumazenil?

A

0.2 mg IV and titrate to consciousness, give 0.1 mg every minute up to 1 mg total, or return to consciousness.

68
Q

What is the dosing of Flumazenil to reverse sedation?

What is the dosing of Flumazenil for OD BZD?

A

0.3 to 0.6 mg

0.5 to 1.0 mg

69
Q

What to do if the patient is still unconscious after using 1.0 mg of flumazenil?

A

Use other intoxicants like Narcan.

70
Q

What is the duration of flumazenil?

What is the continuous infusion rate of flumazenil?

A

30-60 minutes (half-time for BZD are longer, may need to redose)

0.1 to 0.4 mg/hr

71
Q

What are the side effects of flumazenil?

What are the special considerations to take when using flumazenil?

A

None

Contraindicated if BZDs are used as an antiepileptic drug, can precipitate acute withdrawal seizures.

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

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