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Anesthesia Pharmacology > Benzodiazepines > Flashcards

Benzodiazepines Flashcards

Test 1

1
Q

Whats the difference between a sedative and a hypnotic?

A

sedative: induces calm or sleep

hypnotic: induces hypnosis or sleep

both share similarities with anesthesia

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2
Q

What does sedative/hypnotics inhibit?

A

Thalmic & mid brain RAS
CNS

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3
Q

T/F: some people will have awareness under general anesthesia

A

T

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4
Q

What is a good range for BIS monitoring to be between? What does it mean when they are within this range? Below this range?

A

40 - 60

Within: Probably will have no recall

Below: Too deep

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5
Q

What are the 4 components of BIS monitors? And what do they tell us?

A
  1. SQI (signal quality index)
  2. EMG: tell us if the patient is about to move. You shouldn’t have EMG movement if patient is paralyzed.
  3. EEG
  4. SR (suppression ratio): how much of time within the last few minutes has the BIS # been 0
    you should never have a number for this
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6
Q

How do synergistic anesthetics affect the BIS number?

A

Decreases it

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7
Q

How does ketamine affect the BIS number?

A

Increases it

Ketamine is a sympathomimetic and stimulates the CNS and causes the brain to be more active while being in an anesthetic state

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8
Q

How does beta blockers affect the BIS number?

A

Decreases it

Peripheral nervous system is stimulated so CNS like it’s more suppressed

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9
Q

When taking drugs that may artificially manipulate the BIS number, we are more interested in _________

A

trends

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10
Q

What are the pharmacological effects of benzodiazepines?

A

SAAAS

Sedation
Anxiolytics
Anterograde amnesia
Anticonvulsant
Spinal-cord mediated skeletal muscle relaxation

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11
Q

Anterograde amnesia in benzos lasts ______ than sedative effects

A

longer

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12
Q

What are reasons that we give benzodiazepines over barbiturates?

A
  1. Less risk for increased tolerance
  2. Less risk for abuse
  3. Fewer serious side effects
  4. Don’t induce hepatic microsomal enzymes
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13
Q

All benzos are structurally & chemically ______

A

similar

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14
Q

The antagonist for benzos is considered __________. What does this mean?

A

Nonspecific

This means if given, will affect any benzos that have been taken

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15
Q

What is the antagonist for benzos? (reversal agent)

A

Flumazenil/Romazicon

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16
Q

Midazolam is most commonly used in ________. Why?

A

Pre/Periop

Quick onset, shorter half time, and prompt recovery

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17
Q

What is the MOA of benzos?

A

Facilitates action of GABA, which is a main inhibitory neurotransmitter in the CNS, at GABAA receptors which are located in lipid bilayers.

This allows the receptor to open and Cl- to hyperpolarize the postsynaptic membrane –> more resistant to depolarization

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18
Q

Where do benzos bind on the GABA-A receptor?

A

Alpha1-gamma
Alpha2-gamma

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19
Q

What is the difference between the Alpha 1 and Alpha 2 subunit?

A

Alpha1: most abundant type
-sedative, amnestic, anticonvulsant
-cerebral cortex, cerebellar cortex, thalamus

Alpha2: anxiolytic, skeletal muscle
-hippocampus, amygdala

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20
Q

What are other things that bind to GABA-A receptor binding sites? Why does this matter?

A
  1. Barbiturates
  2. Etomidate
  3. Propofol
  4. Alcohol
  5. Volatiles

Synergistics increase risk for overdose & tolerance

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21
Q

All benzos have a ______ lipid solubility & ______ protein bound

A

high

highly

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22
Q

How do benzos affect your EEG?

A

Decreased alpha activity

Some can produce isoelectric state

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23
Q

Which benzo does not produce in isoelectric state in EEGs?

A

Versed/Midazolam

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24
Q

What things cause synergistic affects with benzos?

A
  1. Barbiturates
  2. Etomidate
  3. Propofol
  4. Alcohol
  5. Volatiles
  6. Opioids
  7. Alpha-2 agonists
  8. Injected anesthetics
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25
Q

Benzos ______ platelet aggregation by doing what?

A

inhibit

preventing the conformational change in the platelet membrane to be able to grab on to each other

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26
Q

Midazolam is made with a _______ ring. How does this effect the pharmacokinetics?

A

Imidazole

-Stabilize the structure
-Allows rapid metabolism

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27
Q

Which is more potent Midazolam/Versed or Diazepam/Valium? Why?

A

Midazolam (2-3x)

Greater affinity for receptor

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28
Q

What is a consideration that we need to have for Midazolam?

A

Since it causes amnesia for several hours, family needs to be present to sign postop paperwork and to drive home

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29
Q

Describe how pH and solubility of midazolam work.

A

In the bottle: Imidazole ring is open
-pH is < 3.5 & protonated form
-water soluble
-stabilzed

When you put in normal blood pH: ring closes
-pH >4.0 & unprotonated form
-lipid soluble
-able to have rapid onset

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30
Q

Pharmacokinetics: Midazolam

Onset; Peak; DOA; Half time; Vd; enzymes

A

Onset: 1-2mins

Peak: 5 mins

DOA: short

Half time: 2 hours
Doubled in elderly, hepatic flow, enzyme activity

Vd: 1-1.5 L/kg (large)
Larger in morbidly obese; smaller in elderly with less fat

Enzymes: CYP450; CYP3A4

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31
Q

What happens during metabolism to midazolam?

A

Active & inactive metabolites

active metabolite: 1-hydroxymidazolam

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32
Q

What drugs cause inhibition of CYP450? What are these?

A

Cimetidine
Antifungals
Fentanyl
Erythromycin
Calcium channel blockers

Drug interactions to midazolam and diazepam

33
Q

Clearance for Midazolam is _____ faster than lorazepam and _____ faster than diazepam.

A

5x

10x

34
Q

How does Midazolam and diazepam both affect CMRO2 and CBF?

A

They both decreased depending on the dose

The more you give the more they are decreased

35
Q

T/F: Midazolam is a potent anticonvulsant in status epilepticus

A

T

36
Q

What effect does Midazolam have on vasomotor response to CO2?

A

It preserves it

It doesn’t affect how blood vessels respond to CO2. Blood vessels will still dilate if CO2 is increased and vice versa.

37
Q

Why is Midazolam good for induction with neuro patients?

A

It causes no change in ICP

38
Q

How does Midazolam effect pulmonary? What are concerns we should have with this?

A

It is dose dependent

-decreases hypoxic drive
-increases depression with COPD (& other respiratory disorders)
-depresses swallowing reflex
-decreases upper airway activity
-transient apnea, if rapid IV w/ opioids

** risk for aspiration**

39
Q

How does Midazolam effect the CVS?

A

Dose dependent

HR: increases
BP: decreases
CO: unchanged
SVR: decreases

40
Q

T/F: Midazolam inhibits BP/HR response to intubation

A

F

41
Q

Dose: Midazolam (child/sedation)

A

0.25 - 0.5 mg/kg PO
peak 20-30 mins

42
Q

Dose: Midazolam (adults/sedation)

A

1 - 5 mg IV

elderly require decreased doses

43
Q

Dose: Midazolam (Induction)

A

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

Give opioid 1st:
1-3 mins beforehand
Fentanyl 50-100 mcq

44
Q

Dosing: Midazolam (maintenance)

A

Uncommon, but can be used

45
Q

T/F: Midazolam is associated with N/V an emergence excitement

A

F

Your patient will not try to fight you when they wake up

46
Q

Dosing: Midazolam (Postop sedation)

A

1 - 7 mg/hr IV

Markedly delayed awakening dt active metabolites accumulation

47
Q

What are the reason reasons why we don’t like to use Midazolam as a drip?

A

Active metabolites accumulation
Immune/ T cell affects

Overall, not good for a long-term

48
Q

Diazepam is soluble in ______ and insoluble in ______

A

lipids

water

49
Q

Which has a longer DOA, midazolam or diazepam?

A

diazepam

50
Q

What is added to diazempam to make is soluble in water and less painful upon injection?

A

Propylene glycol

Also has a soybean formula thats less painful but more expensive

51
Q

Pharmacokinetics: Diazepam

Onset; Peak; DOA; Half time; Vd; enzymes

A

Onset: 1- 5 mins

Peak:

DOA: Shorter than midazolam

Half time: 20 - 40 hours

Vd: 1-1.5 L/kg (large)
Larger in woman than men

enzymes: CYP450/CYP3A

52
Q

Diazepam dissociates _______ from GABA-A receptors than midazolam. What does this cause?

A

faster

shorter DOA

53
Q

What are the active metabolites to diazepam? How do they affect the body?

A

Desmethyldiazepam (48-96 hrs)
Oxazepam

both are nearly as potent as diazepam

return of drowsiness 6 to 8 hours

54
Q

Dose: Diazepam (anticonvulsant/other?)

A

0.1 mg/kg IV

other: DTs, lidocaine toxicity related seizures

55
Q

T/F: diazepam can produce isoelectric on EEG

A

T

56
Q

What are the pulmonary affects that diazepam has?

A

-minimal effects on ventilation
Slight decrease tidal volume
-affects exaggerated with synergistic drugs or existing respiratory disorders

57
Q

What can reverse respiratory depressant effects?

A

Surgical stimulation

58
Q

How does diazepam affect the CVS?

A

HR: none
BP: minimal decrease
CO: minimal decrease
SVR: minimal decrease

significant BP changes can occur with synergistic drugs

59
Q

T/F: adding nitrous can significantly lower the BP while giving diazepam due to synergistic effects

A

F

60
Q

Why is diazepam great for cardiac surgery induction?

A

Minimal reduces/changes in hemodynamics

61
Q

Which benzo decreases tonic effect on spinal neuron? What effect does this have?

A

Diazepam

This decreases skeletal muscle tone –> muscle relaxant effecr

they gave me for back pain

62
Q

Dosing: Induction

A

0.5 - 1.0 mg/kg IV

Decrease dose by 25 - 50%
-elderly
-liver disease
-presence of opioids

63
Q

Which benzo is more potent?

A

Lorazepam/Ativan

64
Q

Lorazepam resembles _________ which is a metabolite of __________. What type of extra atom does it have?

A

oxazepam

Diazepam

Chloride

65
Q

Lorazepam is soluble in _______ & insoluble in_______

A

Lipids

Water

66
Q

What do you add to lorazepam/Ativan to make it soluble in water?

A

Polyethylene glycol

67
Q

Pharmacokinetics: lorazepam

Onset; Peak; DOA; Half time; Vd; enzymes

A

Onset: slower than midazolam or diazepam dt lower lipid solubility

Peak: 20 -30 mins with 1-4mg IV

DOA:

Half time: 14 hours

Vd:

enzymes:

68
Q

Why is Ativan good for patients with liver disease or patients just with not a good liver?

A

Lorazepam/Ativan is not entirely dependent on hepatic enzymes. They can directly conjugate to inactivate metabolites.

69
Q

Why is lorazepam the better choice for a benzo for a long term drip?

A

-cost-efficient
-conjugated to inactive metabolites
-can directly conjugate without hepatic enzymes

70
Q

T/F: if your patient is actively fighting, you, lorazepam is a great choice

A

F

Slower onset of action and longer peak effect

71
Q

Describe the organ effects in lorazepam

A

Similar to other benzos

72
Q

Dosing: lorazepam (single dose)

A

1 - 4 mg IV

73
Q

Flumazenil/Romazicon is a _________ antagonist with a _____ affinity for the Benzo receptor

A

Competitive

High

74
Q

How is Flumazenil/Romazicon metabolized?

A

The hepatic enzyme, hepatic esterase, into inactive metabolites

75
Q

Dosing: Flumazenil/Romazicon

A

–0.2 mg IV initial dose
0.1 mg subsequent doses until consciousness or 1 mg total

Sedation: 0.3 - 0.6 mg

Abolished therapeutic dose: 0.5 - 1.0 mg

76
Q

What happens if you give 1 mg of Flumazenil/Romazicon and nothing changes?

A

They have something else in their system, then benzos. Move on to other antagonist/reversal agents

76
Q

What is the DOA of Flumazenil/Romazicon?

A

30 - 60 mins

77
Q

What are the side effects of Flumazenil/Romazicon?

A

No side effects other than reversing benzos

Ex) think! Could be taking these benzos for seizures or DTs. Those pathos can become present.

Anesthesia Pharmacology (4 decks)

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