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Anesthesia Pharmacology > Lecture 3 - Benzodiazepines (Test 1) > Flashcards

Lecture 3 - Benzodiazepines (Test 1) Flashcards

1
Q

What is the principal inhibitory neurotransmitter in the CNS?

A

Gamma-aminobutyric acid (GABA)
Slide 14

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2
Q

Benzodiazepines facilitate action at which receptor?

A

GABA-A Chloride Ionophore
Slide 14

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3
Q

By enhancing the affinity of the receptors for GABA, we also enhance which type of channels?

A

Chloride channels
(Slide 14)

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4
Q

Which GABA subunit is the most abundant and induces sedation, amnesia, and is also has anticonvulsant properties?

A

Alpha-1
Slide 15

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5
Q

Which GABA subunit works as an anxiolytic and has more effects on skeletal muscles?

A

Alpha-2
Slide 15

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6
Q

True or False
Benzodiazepines sit on their own site within the GABA receptor.

A

True
Slide 15

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7
Q

Opposed to alpha-1 and alpha-2, which receptor subtype sits outside the CNS?

A

Alpha-5
Slide 15

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8
Q

Which other GABA-A receptor binding sites are right beside the benzo sites?

A

Barbiturates
Etomidate
Propofol
Alcohol
*Can cause synergistic effects

Slide 16

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9
Q

Barbiturates, Etomidate, Propofol, and Alcohol have what type of effect when combined with benzos?

A

Synergistic
Slide 16

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10
Q

Are benzos highly protein-bound and lipid-soluble? What does this mean in regard to Vd?

A

Yes, 98%
They have a large volume of distribution due to the lipid solubility, but there is not a large amount of free drug to distribute because of the protein binding.
Slide 17

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11
Q

If you give a patient with cirrhosis or renal failure Versed, what would you expect?

A

A prolonged effect due to the drug not being metabolized/excreted.

Slide 17

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12
Q

Benzodiazepines decrease __________ activity on an EEG?

A

Alpha wave

Slide 19

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13
Q

Do benzodiazepines cause antegrade or retrograde amnesia? What does this mean?

A

Antegrade - The pt won’t remember anything after the drug is given
Slide 19

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14
Q

Benzodiazepines have synergistic effects with what type of drugs?

A

Alcohol, injected anesthetics, opioids, alpha-2 agonists, and inhaled anesthetics
Slide 20

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15
Q

Benzodiazepines can inhibit _____________ without the normal conformational change.

A

Platelet aggregation
Slide 21

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16
Q

Why is Valium (Diazepam) not used often in anesthesia?

A

prolonged duration of action compared to midazolam

(slide 35)

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17
Q

Valium’s onset of action is?

Elimination 1/2 time?

A

onset: in 1-5 mins

Elimination 1/2 time: in 20-40 hours

(slide 37)

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18
Q

Is Valium water soluble or insoluble?

A

water INSOLUBLE

(slide 36)

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19
Q

What additive is used in valium for IV administration that causes a burning pain on injection?

A

Propylene glycol

(slide 36)

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20
Q

Which dissociates from GABA receptors faster, Diazepam or Lorazepam?

Which has a longer E 1/2 time?

A

Diazepam, diazepam.

(slide 37)

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21
Q

What pathway metabolizes Diazepam?

A

CYP3A pathway

( - Kane)

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22
Q

What risk factors prolong effects of Diazepam?

A
  • Hepatic failure/Cirrhosis
  • Age (elderly d/t increased Vd 2/2 increased body fat)

(slide 37)

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23
Q

6-8 hours after admin of Valium, what are we most concerned about? (Hint: especially outpatient surgeries)

A

Return of drowsiness 2/2 valium’s active metabolites
(Kane mentioned the scenario with grandpa going home after sx and taking a nap to be found dead later from severe resp. depression d/t to the valium’s active metabolites)

(slide 38)

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24
Q

Which benzo can produce isoelectric EEG?

A

Diazepam

(slide 39)

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25
Q

Out of Versed, Ativan and Valium, which one would cause minimal decrease in BP, CO, and SVR even with induction doses?
(Hint: It used to be used for cardiac surgery induction*)

A

Valium (Diazepam)

(Slide 41)

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26
Q

If you give Valium (Diazepam) and you see a change in BP, what could be the cause?

A

Additives such as opioids & propofol!

Valium alone will not cause a change in BP!

(Slide 41)

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27
Q

Which has more effect on respiratory drive - Midazolam or Diazepam?

A

Midazolam

Diazepam has “minimal effects on ventilation” but can be exaggerated with opioids, ETOH, and COPD

(slide 40)

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28
Q

Depending upon the dose of Versed, what effects does it have in cardiovascular system?

A

↑ HR and ↓BP
slide 29
(↓BP is thought to be due to ↓ in SVR)

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29
Q

If you have given nitrous to your patient and then given Valium (Diazepam) would you expect to see a change in BP?

A

NO!

Nitrous is an additive that will not effect BP when given with Valium!

(Slide 41)

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30
Q

Does versed alter cardiac output?

A

No.
slide 29
(Versed ↓SVR, the compensatory effect is to ↑HR to maintain CO)

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31
Q

What benzo is known to be a potent anticonvulsant?

At what dose and route per the powerpoint?

Which types of seizures is this med known to treat particularly well?

A

Valium (Diazepam)

Dose: 0.1 mg/kg IV

Known to be effective in treating: Delirium Tremens, Status Epilepticus, and Lidocaine toxicity related seizures

(slide 39)

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32
Q

Besides Valium, what are some other known longer acting anticonvulsants?

A

Fosphenytoin and Cerebryx

(slide 39)

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33
Q

Which benzodiazepine was used as a muscle relaxant back in the day before flexeril was invented (decreased tonic effect on spinal neuron)?

(Hint: people developed tolerance to its muscle relaxation properties & it has no action at neuromuscular junction!)

A

Valium (Diazepam)

(Slide 43)

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34
Q

Do you give versed to pt who is in hypovolemic shock, or hemorrhaging?

A

No
slide 29
(Versed further decreases BP)

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35
Q

What is the induction dose for Valium (Diazepam)?

A

0.5-1.0 mg/kg IV
(Slide 44)

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36
Q

In what 3 patient population do we decrease the dose of Valium by 25-50%?

A

*Elderly
*Liver disease
*Presence of opioids
(Slide 44)

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37
Q

So Dr. Kane mentioned that Valium (Diazepam) can cause a “slight decrease in tidal volume” but what stimulation is adequate to temporarily reverse this mild ventilatory depressant?

A

Surgical stimulation (so resp. drive isn’t much of a concern intra-op but keep in mind the long elimination 1/2 time for post-op)

(slide 40)

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38
Q

What is the most potent sedative and amnestic compared to Midazolam and Diazepam?

A

Lorazepam (Ativan)

Slide (45)

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39
Q

Lorazepam (Ativan) resembles Oxazepam (Serax) because?

A

Oxazepam has an extra Cl- atom!
(Oxazepam is an active metabolite of Temazepam)

(Slide 45)

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40
Q

T/F
Ativan is insoluble in water therefor it requires a solvent such as propylene glycol for preparation.

A

True

(Slide 46)

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41
Q

When would Versed (midazolam) not inhibit the associated HR/BP responses?

A

During intubation.

slide 29
(This response is good when someone comes with hypotension.
Intubation will help stimulate the sympathetic system to offset the decrease in BP)

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42
Q

True or false: BIS level changes are correlated to the patients movement?

A

True

(slide 8)

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43
Q

What BIS level range do we want to achieve to represent adequate general anesthesia?

A

Want: 40-60 range
(ranges from 0-100)

(slide 8)

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44
Q

What does a low BIS level represent?

A

low brain activity and less likely to move

(slide 8)

45
Q

What does a high BIS level represent?

A

Awake state and more likely to move

(slide 8)

46
Q

When monitoring BIS levels, what does the “High Dose Narcotic Technique” cause to the reading?

A

Less correlation between BIS and movement
(when little to no other general anesthetic is given with opioids)

(slide 8)

47
Q

Compared to Midazolam and Diazepam, Lorazepam has a ________ onset of action, _________ lipid solubility, and _______ metabolic clearance.

A

Slower, Lower, Slower

(Slide 46)

48
Q

During BIS studies: Were patients with a BIS <58 conscious or unconscious?

A

unconscious

(slide 8)

49
Q

During BIS studies: Patients with a BIS <65 had a less than 5% chance of returning to consciousness within how long?

A

50 sec.
(under 1 min- per Dr. Kane)

(slide 8)

50
Q

On the BIS monitor, what does the SQI reading stand for and show?

A

Signal Quality Index.
- Predicts the reliability of the signal vs artifact. The higher the SQI, the more reliable is the BIS number.

(slide 9)

51
Q

On the BIS monitor, what does the EMG reading stand for and show?

A

Electromyographic
- Reflects muscle stimulation caused by an increase in muscle tone/tightness or muscle movement. (even if we do not see them initially moving, it can tell us if they are about to move)

(slide 9)

52
Q

What are the 5 main pharmacological effects that Benzodiazepines do?

A
  1. Anxiolytic
  2. Sedation
  3. Anterograde amnesia
  4. Anticonvulsant
  5. Spinal-cord mediated skeletal muscle relaxation (used these before muscle relaxers were invented)

(slide 11)

53
Q

Yes or No: Are people who go to sleep (get sedated) while they are anxious and scared likely to wake up anxious and scared?

A

Yes!
(Why we want to give a anxiolytic Benzodiazepine before hand - want to go to sleep calm and wake up calm)

(slide 11)

54
Q

Define Anterograde amnesia:

A

From the time the medication is given and forward, will have loss of memory.

(slide 11)

55
Q

What is the dose of versed for children? when does it peak?

A

0.25 - 0.5 mg/kg oral and peaks in 20-30 minutes
slide 30
(makes sure you give it 20-30 minutes prior to going OR)

56
Q

Yes or No: Does Amnesia last longer than the sedative effects?

A

Yes!

(slide 11)

57
Q

Define Retrograde Amnesia:

A

Loss of memory where you can’t recall memories that were formed before the event that caused the amnesia. It usually affects recently stored past memories, not memories from years ago. Only known Rx to cause Retrograde Amnesia is Electroconvulsive Therapy

(slide 11)

58
Q

What is the difference between a sedative and hypnotic? What common effect do they both have?

A

Both induce sleep. Sedative also induces calm. Hypnotic also induces hypnosis. (Slide 2)

59
Q

What similarities does anesthesia share with sleep? (Hint: brain related)

A

Both will inhibit thalamus and mid brain RAS (reticular activating system), can reversibly inhibit CNS. (Slide 2)

60
Q

Some studies suggest anywhere from 1/1000 to 1/10000 people will experience _______ under anesthesia. Very traumatic.

A

Awareness, consciousness. Some awareness can be normal during sedation only cases and emergence, but should not be normal during general anesthesia. (Slide 3)

61
Q

What are the 4 main reasons we replaced Barbiturates with Benzodiazepines for preop sedation in anesthesia?

A
  1. Less tolerance
  2. Less potential for abuse
  3. Fewer/less serious side effects
  4. Does not induce hepatic microsomal enzymes (CYP450)

(slide 12)

62
Q

In comparing Barbiturates with Benzodiazepines: Do they share a similar structure? (Y/N)

A

Yes

(slide 13)

63
Q

what is Benzodiazepines pharmacologic antagonist?

A

Flumazenil

(slide 13)

64
Q

Is Midazolam most commonly used during perioperative or postoperative period?

A

Perioperative- for prompt recovery

(slide 13)

65
Q

Is Diazepam/Lorazepam most commonly used during the perioperative or postoperative period?

A

Postoperative- have a much greater 1/2 time than that of Midazolam

(slide 13)

66
Q

When giving anesthesia, EEG monitoring can be used to help monitor what 2 brain related values?

A

CBF (cerebral blood flow) and CMRO2 (cerebral metabolic rate of oxygen).
Higher CBF and CMRO2 = more awake. Lower = less awake.

Anesthesia can lower these values. By combining EEG monitoring with anesthesia, we can help find the sweet spot where a pt is asleep but not dying. (Slide 5)

67
Q

What is the dose of versed for adults? When does it peak?

A

1 - 5 mg IV and peaks in 5 minutes
Slide 30
(Decrease dose in elderly, greater CNS sensitivity to versed)

68
Q

To reverse NMB, ______ is used with atropine or _________.

A

Neostigmine, Robinul
slide 29
(Neostigmine can cause bradycardia and Robinul can cause tachycardia, so these drugs are given together to cancel out the side effect of each other)

69
Q

What is the dosage of Versed given for induction to adults?
Would you give an opioid?

A

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

With 50-100mcg of fentanyl over 1 -3 min (can be given before benzo or immediately after)

Slide 32

70
Q

What are the benefits of using maintenance dosing of versed?

A
  1. It can give synergistic effects with opioids, propofol, and volatiles.
  2. decrease requirements for volatiles (depends on the versed dose).
  3. Rarely associated with N/V or emergence excitement.
    Slide 33
71
Q

What is the dosage for postoperative sedation (Midazolam) if the patient is still intubated?

A

1-7 mg/hr IV
Slide 34

72
Q

Why does Versed cause a delay in awakening with maintenance dosage?

A

Due to the accumulation of active metabolite while running as a drip. Its clearance depends on hepatic metabolism, not redistribution.

Slide 34

73
Q

What are the critical care medicine sedation guidelines regarding running versed drip?

A

Versed should not run more than 2-3 days because in the lab it shows an alteration in the ability of the T- cells to mount an immune response. So the patients are more prone to infection.
Slide 34
(but unclear clinical significance)

73
Q

What is the peak effect of IV Lorazepam (Ativan)?

A

20-30 mins

Slide 47

74
Q

What is the elimination halftime of lorazepam (Ativan)?

A

14 hrs

Slide 47

75
Q

Lorazepam (Ativan) is better suited for day-to-day use vs for induction/OR.
True of False?

A

True!

Slide 47

76
Q

Lorazepam (Ativan) relies heavily on the CYP450 enzymes.
True of False?

A

False!
It has a slower metabolism…
This means it is safer to use in liver disease patients and won’t affect other drugs concentration like versed and valium would. (Bc they inhibit CYP450)

Slide 47

77
Q

Lorazepam (Ativan) has similar organ system effects as other benzo’s. It is also good as a gtt for ____ sedation or ____ longterm.

A

Post-op, PO

Slide 48

78
Q

What is the IV dose for Lorazepam (Ativan) if the patient is hallucinating or acting crazy?

A

1 - 4 mg IV

Slide 49

79
Q

What is the antagonist for benzo’s? And what type of antagonist is it? (Competitive or non-competitive)

A

Flumazenil (Romazicon)
Competitive Antagonist! -it will reverse or prevent all benzo activity on the benzo receptor.

Slide 50

80
Q

Flumazenil (Romazicon) is metabolized by _____ _____ _____ to _____ metabolites and is eliminated.

A

Hepatic microsomal enzymes, inactive

Slide 51

81
Q

What is the initial dose of Flumazenil (Romazicon)?

What is the titrating dose after the initial dose?

A

Initial: 0.2 mg IV

Titrate (to consciousness): repeated 0.1mg q1min to 1mg total

Slide 52

82
Q

If you’re trying to reverse sedation, expect to give ___ - ___mg of Flumazenil (Romazicon).

If unconscious or OD on benzo’s, expect to give ___-___mg.

A

Reverse sedation: 0.3 - 0.6mg

OD: 0.5 - 1mg
*if you give all this & still unconscious - you’re problem is something else.
(Narcan, Banana bag, hepatic encephalopathy?)

Slide 52

83
Q

If you overdose your patient on versed (midazolam) (E 1/2 = 2 hrs), you know you will have to give repeated doses of Flumazenil (Romazicon) bc its duration is only ___ - ___ mins.

What’s the continuous infusion rate?

A

30-60 mins
*cont infusion (0.1 - 0.4 mg/hr)

Slide 52

84
Q

What are the side effects of Flumazenil (Romazicon)?

A

Really, none. :D

Slide 53

85
Q

What chemistry characteristic is specific to Benzos

A

Imidazole ring

Slide 22

86
Q

What are midazolam’s chief indications?

A

PreOp (anti-anxiety) and conscious sedation

Slide 22

87
Q

You give the pt a hefty dose of Versed (Midazolam) in pre-op. The surgeon arbitrarily cancels the case and you want to give Flumazenil (Romazicon) to reverse the benzo.
You check the pt hx again and see your patient suffers from epilepsy and is on multiple AED’s.

Is it okay to proceed with the Flumazenil? Explain your answer.

A

No…
This will void their AED’s and could precipitate acute withdrawal seizures.
*You should try to reverse narcotic (if they had any) first!

Slide 54

88
Q

True or False. It is harder to perform conscious sedation in the OR than general anesthesia.

A

True

Slide 22

89
Q

What other Benzo is Midazolam 2-3x as potent?

A

diazepam (valium)

Slide 22

90
Q

With Midazolam, _______ effects last longer than _______ effects

A

Amnesia. Sedation

Slide 22

91
Q

For Midazolam….
In a pH environment < 3.5 the ring structure is _______.
In a pH environment > 4.0 the ring structure is _______.

A

Open
Closed

Slide 23

92
Q

For Midazolam….
It is lipid soluble and unprotonated in a pH environment of ______.
It is water soluble and protonated in a pH environment of _______.

A

> 4.0
< 3.5

Slide 23

93
Q

True or False. Midazolam burns when injected.

A

False

Slide 23

94
Q

What is the onset time of action for Versed?

A

1- 2 minutes (IV)

Slide 24

95
Q

What is the time for peak effect for Versed?

A

5 minutes
Be patient and let it work….or youll kill somebody geez…

Slide 24

96
Q

Why does Versed have a short duration?

A

Versed is lipid soluble but it does not stay on the receptor for long periods. It rapidly redistributes. This is good for us!
Slide 24

97
Q

E 1/2 time for Versed?

A

2 hours
Doubled for elderly patients.

Slide 25

98
Q

Volume of Distribution for versed…

A

1- 1.5 L/kg
Very lipid soluble.

Slide 25

99
Q

What is an active metabolite of Versed?

A

1 - hydroxymidazolam
1/2 the activity of the parent

Slide 26

100
Q

Drugs that cause inhibition of P-450 enzymes (decreases BZD metabolism)

A

Cimetidine
Erythromycin
Calcium Channel Blockers
Antifungal
Fentanyl

Slide 26

101
Q

Midazolam clearance is __ times faster than ativan and ___ times faster than valium.

A

5
10

Slide 26

102
Q

What are the 6 CNS effects of Versed mentioned in lecture?

A

Decreased Cerebral Metabolic Requirement of Oxygen
Decreased Cerebral Blood Flow
Does not produce isoelectric EEG
Potent anticonvulsant
Preserves vasomotor response to CO2
No change in ICP

Slide 27

103
Q

What are the 3 pulmonary effects of versed mentioned in lecture?

A

Dose Dependent decreases in ventilation
Depresses swallowing reflex
Decreases upper airway activity (coughing)

Slide 28

104
Q

In the OR, instead of an impractical 12-20 lead EEG machine, we use _____ instead.

A

BIS aka Bispectral Analysis. (Slide 7)

105
Q

What is BIS? How was it created?

A

Bispectral Analysis. This was created in 1996 by combining data from 1500 subjects and 5000 hours of EEG. BIS interprets EEG like information from the patient and puts that data into a mathematical algorithm. The mathematical algorithm then gives you a score that indicates your level of consciousness. (Slide 7)

106
Q

What medications did they use when creating/testing BIS?

A

A combination of isoflurane/oxygen, propofol/nitrous, and propofol/alfentanil. (Slide 7)

107
Q

Versed decreases what two things in the CNS?

A

Cerebral Blood Flow
Cerebral Metabolic Requirement of Oxygen

Slide 27

Anesthesia Pharmacology (20 decks)

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