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Adv Anes. Pharm Spring 2024 > Exam 1/ Lecture 3: Benzodiazepines > Flashcards

Exam 1/ Lecture 3: Benzodiazepines Flashcards

1
Q

Lecture 1/24/24

What is the definition of a Sedative

A

a drug that induces calm or sleep

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2
Q

Lecture 1/24/24

What is the definiton of a Hypnotics?

A

a drug that induces hypnosis or sleep

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3
Q

Lecture 1/24/24

True or false: The definitions for sedative and hypnotics can be use interchangeablely.

A

True

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4
Q

Lecture 1/24/24

What are the 2 main similarities that sedatives and hypnotics have with anesthesia?

A
  • Inhibits thalamic and mid -brain RAS (Reticular Activating System)
  • Rerversibly inhibits CNS

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5
Q

Lecture 1/24/24

A patient that experieces active recall from a surgery (smell burning tissue, hear the saw, feel the pain) can develop what type of mental disorder?

A

PTSD

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6
Q

Lecture 1/24/24

Is unconsciousness described as a single state (yes/no) or a continuum?

A

Continuum

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7
Q

Lecture 1/24/24

What happened in 1937 regarding EEG monitoring?

A

EEG could be use to measure effects

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8
Q

Lecture 1/24/24

What happened in 1952 regarding EEG monitoring?

A

Depth of Anesthesia correlates with concentration of ether

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9
Q

Lecture 1/24/24

What are 2 observational findings that are related to the depth of sedation and reflected in the EEG activity?

A

Cereberal blood flow
Cerberal metabolic oxygen demands

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10
Q

Lecture 1/24/24

What can alter the cereberal blood flow and cerberal metabolic oxygen demands?

A

Anesthesia

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11
Q

Lecture 1/24/24

When placing leads on a patient for a electroencephalogram what does these abbreviation stand for:
* F =
* C =
* T =
* P =
* O =
* A =
​

A
  • F = Frontal
  • C = center
  • T = Temporal
  • P = Parietal
  • O = Occipital
  • A = Auditory

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12
Q

Lecture 1/24/24/

When placing leads on a patient for a elctroencephalogram what letter/lead can the CRNA use as a reference point?

A

Z

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13
Q

Lecture 1/24/24

What side were the odd and even number EEG leads placed on the patient head?

A

Odd - Left
Even -Right

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14
Q

Lecture 1/24/24

In 1996, what type of technology was created?

A

Bispectral Analysis (BIS)

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15
Q

Lecture 1/24/24

What are the 3 combination of anesthesia drugs that were used to test the bisepectral analysis (BIS)

A
  • isoflurane/oxygen
  • propofol/nitrous
  • propofol/alfentanil

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16
Q

Lecture 1/24/24

After removing the high and low frequency artifact on a BIS, what did the company develop that assessed the consciousness of the patient?

A
  • Mathematical algorithm based on the pattern, time, frequency, and amplitude

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17
Q

Lecture 1/24/24

What type of drugs cause the BIS to change in correlation to the patient movement?

A

Hypnotic drugs

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18
Q

Lecture 1/24/24

Less correlation is seen between the BIS reading and patient movement when a narcotic is administered at a ________ dose

A

High

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19
Q

Lecture 1/24/24

True or False: A patient with a BIS of 23 is conscious

A

False, No patient with BIS < 58 was conscious

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20
Q

Lecture 1/24/24

What level of the BIS would determine that a patient had a less than 5% chance of returning to consciousness within 50 seconds?

A

BIS <65

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21
Q

Lecture 1/24/24

What are 3 brands of BIS monitoring device today?

A

PSA (Patient State Index)
Narcotrend
GE Entropy

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22
Q

Lecture 1/24/24

What are the abbreviation and mean to these 4 abbreviation on BIS?
* SQI
* EMG
* EEG
* SR

A
  • SQI (Signal quality index) – the quality of the signal – good or bad signal
  • EMG (Electromyography) – reflects muscle stimulation caused by increased muscle tone or movement
  • EEG (Electroencephalogram) – individual brain signals compressed into one signal
  • SR (suppression ratio) - tells you in the last 30 sec - 60 secs how long the BIS remain at 0

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23
Q

Lecture 1/24/24

What 4 medication class examples that will cause a depression in the BIS number?

A
  • Hypnotics
  • Volatiles
  • NMBD
  • Opioids

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24
Q

1/24/24

What 2 examples of mediction that would cause an increase in the BIS

A
  • Ketamine
  • epinephrine

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25
Q

Lecture 1/24/24

True or False: Beta blockers will cause a depression in the BIS

A

True

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26
Q

Lecture 1/24/24

What is the range per company that BIS number should display to reflect that the patient is adequately sedated?

A

40 - 60

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27
Q

Lecture 1/24/24

A patient BIS trend lower than 40 could be a correlation of what depth of sedation?

A

deep sedation

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28
Q

Lecture 1/24/24

A patient BIS trend higher than 60 could be a correlation to what depth of sedation?

A

Mininal sedation

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29
Q

Lecture 1/24/24

What are the 5 pharmacologic effects of benzodiazepines?

A
  • anxioltics
  • sedation
  • anterograde amnesia
  • anticonvulsants action
  • Spinal -Cord medicated skeletal muscle relaxation

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30
Q

Lecture 1/24/24

What is the difference between anterograde and retrograde amnesia?

A

Retrograde amnesia is when you can’t recall memories from your past. Anterograde amnesia is when you can’t form new memories but can still remember things from before you developed this amnesia

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31
Q

Lecture 1/24/24

Benzodiazepines cause what type of amnesia to patients?

A

Anterograde amnesia

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32
Q

Lecture 1/24/24

Which type of amnesia last longer than the sedative effects?

A

Anterograde Amnesia

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33
Q

Lecture 1/24/24

What type of benzodiaepine was given via rectum as an anticonvulsant and can be use as a skeletal muscle relaxant?

A

Valium

Slide 11

34
Q

Lecture 1/24/24

Benzodiazepines replace which class of drug?

A

Barbiturates

Slide 12

35
Q

1/24/24

what are organ system effects: Pulmonary of Midazolam/Versed

A

Dose-dependent decreases in ventilation
-Decreases hypoxic drive
-depression with COPD
-Transient apnea if rapid IV esp. with opioid

Depresses swallowing reflex

Decreases upper airway activity

Slide 28

36
Q

Lecture 1/24/24

Which specfic benzodiazepine does the pharmacologic works the best on?

A

Versed

Slide 13

37
Q

1/24/24

what are organ system effects: Cardiovascular of Midazolam/Versed

A

Dose dependent increased HR, decreased BP

Cardiac output unchanged
SVR decreased
Helpful in pts with CHF??? - yes

Enhanced hypotension with hypovolemia

Does NOT inhibit BP/HR response to intubation
Offsets hypotension noted above?

slide 29

38
Q

Lecture 1/24/24/

What are the 4 main comparison stated in class regarding comparing the benzodiaepines to each other?

A
  • Structurally similar
  • Specific pharmacologic antagonist ???
  • Midazolam most commonly used in perioperative period
  • Diazepam / lorazepam has much greater ½ time than midazolam and more attractive for sedation postop

Silde 13

39
Q

Lecture 1/24/24

Why do they CRNA use less ativan/ lorazepam now then in the past for post -op sedation management?

A

Due to the developement of precedex

Slide 13

40
Q

1/24/24

what is the Dosing for Sedation with Midazolam/Versed?

A

Preop/intraop sedation/anxiolysis

0.25-0.5 mg/kg oral (children)
Peak 20-30 minutes

1-5 mg IV (adults)
Peaks 5 minutes
Elderly require decreased doses…..Greater CNS sensitivity

slide 30

41
Q

1/24/24

A

Midazolam Safety in Children: Preop : po 30 minutes before induction

slide 31

42
Q

1/24/24

what is the Dosing for Induction with Midazolam/Versed?

A

Dose: 0.1-0.2 mg/kg IV over 30-60 seconds

Facilitated by preceding dose of opioid
1-3 minutes
Fentanyl 50-100 mcq

slide 32

43
Q

1/24/24

Midazolam/Versed Dosing: Maintenance

A

Maintenance

Uncommon
-Can be used to supplement opioids, propofol, and volatiles
-Decreases requirements for volatiles
-Dose dependent manner

Rarely associated with N/V or emergence excitement

slide 33

44
Q

1/24/24

Midazolam/Versed Postoperatvie Sedation

A

Dose: 1-7 mg/hr IV

Markedly delayed awakening
Active metabolites accumulate
Clearance depends on hepatic metabolism not redistribution

Society of Critical Care Medicine sedation guidelines
2-3 days
Immune/T cell effects (versed has negative effects on)
Unclear clinical significance

slide 34

45
Q

1/24/24

Diazepam/Valium is…

A

Highly lipid soluble

More prolonged duration of action than midazolam

Rarely used in anesthesia
Midazolam so beneficial

slide 35

46
Q

1/24/24

Diazepam/Valium Preparation

A

Dissolved in organic solvents
Insoluble in water
Propylene glycol…pain on injection; glycol toxicity
Soybean formulation…less painful

slide 36

47
Q

1/24/24

Diazepam/Valium Pharmacokinetics

A

Onset 1-5 minutes

E ½ time
20-40 hours….extensively protein bound
Similar Vd to midazolam
d/t lipid solubility (larger…women vs men)

Effects prolonged
Hepatic failure/cirrhosis
Age

Dissociates from GABAa faster than lorazepam
Shorter duration of action….longer elimination ½ time

slide 37

48
Q

1/24/24

Diazepam/Valium Metabolism

A

Cytochrome CYP3A pathway

Active metabolites
-Desmethyldiazepam* (48-96 hours) and oxazepam
-Nearly as potent as diazepam
-Return of drowsiness 6-8 hours

Drug interactions similar to Midazolam

slide 38

49
Q

1/24/24

what are the organ system effects: CNS of Diazepam/Valium?

A

Similar to other BZD’s r/t CMRO2 and CBF

Potent anticonvulsant
-0.1 mg/kg IV
-Abolishes DT’s, status epilepticus, lidocaine toxicity related seizures
-Longer acting antiepileptic drug also administered (fosphenytoin…cerebyx)

Can produce isoelectric EEG

Slide 39

50
Q

1/24/24

what are organ system effects: Pulmonary of Diazepam/Valium?

A

Minimal effects of ventilation
Slight decrease in Vt
After 0.2mg/kg IV increases in PaCO2
Exaggerated with opioids, alcohol, COPD

Ventilatory depressant effects reversed by surgical stimulation

slide 40

51
Q

1/24/24

What are organ system effects: Cardiovascular of Diazepam/Valium

A

Minimal decreases in BP, CO and SVR *even with induction doses
was great for cardiac surgery induction

BP changes that do occur…..
Additive with opioid
Unchanged with addition of nitrous (unlike opioid/nitrous)
Prevents recall

slide 41

52
Q

What is the Cardiovascular effect of
Diazepam (Valium)?

A

did this study looking at an awake patient versus when they gave Valium versus one that had Valium and Nitrous:
* Systolic pretty much unchanged
* Diastolic pretty much unchanged
* heart rate pretty much unchanged
* Pulmonary artery pressures pretty much unchanged.

So again, really solid, really safe.

Slide 42

53
Q

What is the Neuromuscular effect of
Diazepam (Valium)?

A
  • Decreases tonic effect on spinal neuron
  • skeletal muscle tone decreased
  • Develop tolerance to skeletal muscle relaxant effects
  • No action at neuromuscular junction
  • will need Vec, Roc, or Sux

slide 43

54
Q

What is the dosing for Diazepam (Valium)?

A

Induction: 0.5-1.0 mg/kg IV

Decrease dose by 25-50%:
* Elderly
* Liver disease
* Presence of opioids

slide 44

55
Q

What is the MOA of Lorazepam (Ativan)

A
  • Resembles oxazepam (Serax)
  • More potent sedative and amnestic compared to Midazolam and Diazepam

slide 45

56
Q

What is the preparation and onset of action of Lorazepam (Ativan)?

A

Preparation: Insoluble in water and requires solvent (Polyethylene Glycol)

Onset of action:
* slower than Midazolam or Diazepam
* slower entrance to CNS (due to lower lipid solubility)
* slower metabolic clearance

Used for post-op sedative

slide 46

57
Q

What is the Peak Effect and IV dose of Lorazempam (Ativan)?

A

20-30 minutes with 1-4 mg IV dose

Slide 47 and Slide 49

58
Q

How is Lorazepam (Ativan) metabolise?

A
  • conjugaged to inactive metabolites
  • not entirely dependent on hepatic enzymes
    -less affected by hepatic function, age, drugs
    -not as affected by blood flow

slide 47

59
Q

What is the Half-time of Lorazepam (Ativan)?

A

E ½ time 14 hours
* Slower than midazolam
* Glucuronidation slower than oxidative hydroxylation

slide 47

60
Q

What is the organ system effects of Lorazepam (Ativan)?

A
  • similar CNS effects
  • Heart effects
  • Pulmonary effects to other Benzodiazepines

slide 48

61
Q

What is the MOA of Flumazenil (Romazicon)?

A

1,4 imidazobenzodiazepine derivative

  • Competitive antagonist: high affinity for BZD receptor
  • Prevents/reverses all agonist activity of BZD
62
Q

What is the metabolism of
Flumazenil (Romazicon)?

A

It metabolizes to the patient’s microsomal enyzmes and inactive metabolites

63
Q

What is the dose of Flumazenil (Romazicon)?

A

**0.2 mg IV **and titrated to consciousness
- Repeated 0.1mg q 1 minute to 1 mg total

Reversal within 2 minutes
0.3-0.6 mg to reverse sedation
**0.5-1.0 mg **to abolish therapeutic dose

Unconscious/overdose AND 0.5-1mg without change means it is caused by other intoxicants

Slide 52

64
Q

What is the duration of
Flumazenil (Romazincon)?

A

30-60 minutes

Supplemental doses vs continuous infusion (0.1-0.4 mg/hr)

65
Q

What is the side effects and contraindication of Flumazenil (Romazincon)?

A

Side effects: NONE

Contraindication: patients on Benzodiazepine antiseizure drugs (we can precipitate acute withdrawal seizure)

66
Q

Which GABA receptor is primarily associated with the CNS?

A

GABA alpha-2

67
Q

Which is the most abundant GABA receptor?

A

GABA alpha-1

68
Q

Which 4 common drugs bind to GABA-A receptor?

A

Barbiturates, Etomidate, Propofol, Alcohol

69
Q

After the administration of Benzodiazepines there will a _______ in alpha activity

70
Q

The following would have a synergistic effect would occur between Benzodiazepines:

A
  • Alcohol
  • Injected anesthetics
  • Inhaled Anesthetics
  • Opioids
  • Alpha-2 Agonists (Ex: Precedex, Clonidine)
71
Q

Benzodiazepines cause a conformational change in plates by _____ platelet aggregating factor

72
Q

What is type of chemical structure stabilizes Midazolam (Versed)?

A

Imidazole Ring

73
Q

Midazolam (Versed) is ______ times as potent as Diazepam (Valium

74
Q

Midazolam becomes water soluble in what state?

A

When it is protonated at a pH <3.5

75
Q

What is the onset time of Midazolam (Versed)?

A

1-2 Minutes (IV administration)

76
Q

What is the E ½ of Midazolam (Versed)?

77
Q

What is the Volume Distribution of Midazolam (Versed)

A

Vd = 1-1.5 L/Kg

78
Q

The E ½ of Midazolam is doubled in what population?

A

Elderly Patients

79
Q

What effects does a high dose of Midazolam have on CMRO2 (Cerebral Metabolic Rate of Oxygen) and CBF (Cerebral Blood Flow)?

A

Decreases both CMRO2 and CBF

80
Q

Is Midazolam (Versed) a potent anticonvulsant?

A

Yes, even in status epilepticus

Adv Anes. Pharm Spring 2024 (7 decks)

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