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ANESTHESIA PHARM 1 > Benzodiazepines > Flashcards

Benzodiazepines Flashcards

1
Q

sustained state of apprehension and autonomic arousal in response to real or perceived threats

A

anxiety

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2
Q

FEAR OF SUFFERING AND DEATH, LOSS OF CONTROL, AND FRUSTRATION caused by the inability to communicate

A

anxiety

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3
Q

headache, insomnia, nausea, anorexia, dyspnea, palpitations, dizziness, dry mouth, chest pain

A

symptoms: anxiety

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4
Q

diaphoresis (excessive sweating), hyperventilation, tachycardia, etc.

A

signs: anxiety

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5
Q

onset: midazolam

A

30-60sec

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6
Q

peak: midazolam

A

3-5min

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7
Q

duration: midazolam

A

15-80min

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8
Q

postoperative benzodiazepine

A

lorazepam (Ativan)

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9
Q

onset: lorazepam

A

1-2min

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10
Q

peak: lorazepam

A

20-30min

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11
Q

duration: lorazepam

A

6-10hr

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12
Q

preoperative PO benzodiazepine

A

diazepam

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13
Q

elimination half-time: midazolam

A

1.9hr

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14
Q

elimination half-time: diazepam (Valium)

A

43hr

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15
Q

elimination half-time: lorazepam

A

14hr

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16
Q

comprise a category of drugs widely used in anesthesia as anxiolytics, sedatives, and hypnotics

A

benzodiazepines

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17
Q

benzodiazepines: site of action

A

GABAA (gamma-aminobutyric acid) receptors

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18
Q

most lipid soluble (in vivo) clinical benzodiazepine

A

midazolam

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19
Q

benzodiazepines: mechanism of action

1.

2.

A
  1. Hyperpolarization of cell (facilitate opening of GABA-activated Cl- channels, increase of inhibitory effect at the CNS side)
  2. Receptor occupancy determines effect

(anxiolysis < sedation < unconsiousness)

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20
Q

where are GABAA receptors found in the highest density?

A

CEREBRAL CORTEX

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21
Q

20% GABA receptor occupancy: effect

A

anxiolysis

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22
Q

30-50% GABA receptor occupancy: effect

A

sedation

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23
Q

60% GABA receptor occupancy: effect

A

unconsiousness

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24
Q

effects: GABA receptor agonism by clinical use of bendiazepines

1.

2.

3.

4.

A
  1. sedation/hynosis
  2. anxiolysis
  3. anticonvulsant (seizures – epilectic, alcohol withdrawal, etc.)
  4. ANTEROGRADE amnesia
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25
Q

NOT effects of benzodiazepines

1.

2.

3.

4.

A
  1. analgesic effects
  2. antidepressant
  3. antipsychotic
  4. protect against stress of intubation (again, no analgesic effect; will still see sympathetic response to stimuli)
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26
Q

midazolam: pediatric preoperative dosage

A

0.5mg/kg PO 30min before

(15mg max)

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27
Q

midazolam: IV sedation (ICU sedation) dosage

A

0.5-4mg IV load then 1-7mg/hr IV

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28
Q

midazolam: IV induction of anesthesia dosage

A

0.1-0.2mg/kg

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29
Q

diazepam: supression of seizure activity dosage

A

0.1mg/kg

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30
Q

Midazolam: pharmacokinetics

ABSORPTION

1.

2.

3.

A
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31
Q

midazolam: more or less for acute intoxication

A

less (GABA receptors already activated)

32
Q

midazolam: more or less for chronic alchoholic

A

more (tolerance)

33
Q

benzo given for alchohol withdrawal

A

Ativan (lorazepam)

34
Q

GABA receptor addiction issues

A

barbituates (bind to GABA receptors similar to benzos)

35
Q

treatment for local anesthetic induced seizures and alcholism detoxification-related seizures

A

Ativan (lorazepam)

36
Q

mechanism of seizures due to detoxification (alcoholism)

A

withdrawal of agonist from GABA receptors, thus excitatory reaction instead of inhibitory action when ligand is no longer activating

37
Q

midazolam: component of balanced anesthetic

how much can you reduce MAC requirements by administering midazolam preoperatively?

A

as much as 30%

38
Q

midazolam: pediatrics

what juice can you not mix midazolam with?

A

grapefruit juice

will trigger an exaggerated effect

39
Q

midazolam: cross tolerance

what drugs should alert you that pt may have higher tolerance to midazolam?

A

Xanax, Ambien, other benzos

heavy alcohol use/abuse

40
Q

midazolam: pharmacokinetics

PO (pediatrics)

A

50% first pass metabolism

41
Q

Pharmacokinetics: distribution

highly lipid soluble benzodiazepines

(really fast onset times)

A

midazolam, lorazepam

ambien

42
Q

how does lipid solubility affect how ambien is prescribed?

A

ambien has high lipid solubility, therefore fast onset time.

prescribed for those that have trouble falling asleep

43
Q

how does lipid solubility affect how lunesta is prescribed?

A

lunest has low lipid solubility, therefore slow onset time.

lunesta is prescribed for those that have trouble falling asleep

44
Q

midazolam pharmacokinetics: distribution

describe the mechanism that affects how long midazolam works

A

rapid redistribution from the brain – midazolam’s effects begin to wear off when it begins dissociating from receptors in the brain and starts soaking into other tissues

45
Q

midazolam pharmacokinetics: distribution

volume of distribution in elderly and obese

A

Vd is high for elderly and obese, therefore has longer duration of action

46
Q

midazolam pharmacokinetics: protein binding

what percent of protein binding do benzodiazepines exhibit?

A

90-98%

47
Q

midazolam pharmacokinetics: protein binding

describe how hypoalbumenia/ decreased liver function affects midazolam pharmacodynamics

A

hypoalbumenia = decreased albumin

decreased protein binding

increased free drug available

EXAGGERATED EFFECT

48
Q

midazolam: metabolism

pathway for metabolism

A

liver oxidation (cytochrome P450)

any drug that inhibits cyt P450 will cause benzos to hang around longer

49
Q

midazolam: metabolism

how does alcohol affect clearance?

A

alcohol INCREASES clearance of benzos

50
Q

midazolam: metabolism

metabolites?

A

no active metabolites for midazolam

51
Q

midazolam: metabolism

how does metabolism relate to dysphoria/cognitive disfunction in elderly?

A

decreased blood flow, decreased kidney/liver function/flow = decreased metabolism = more free drug available

also, increased Vd = longer duration

52
Q

midazolam: elimination

ESRD – reason to worry?

A

no. although metabolites excreted in urine, metabolites are inactive, thus no real concern.

53
Q

midazolam: central nervous system

how does midazolam affect cerebral metabolic oxygen requirements (CMRO2) and cerebral blood flow?

A

decreased CMRO2

decreased CBF, therefore, decreased risk of high ICP

54
Q

midazolam: CNS

EEG?

A

no isoelectric EEG

55
Q

midazolam: CNS

neuroprotection?

A

no evidence of neuroprotection

56
Q

midazolam: ventilation

describe concern for synergistic effects of midazolam with fentanyl

A

midazolam has dose dependent decrease in respiration. synergism with (high doses of) fentanyl can induce apnea

57
Q

midazolam: cardiovascular

how does midazolam affect bp and hr?

A

MINOR decrease in bp, increase in hr

58
Q

midazolam: liver

how do drugs and age affect how the liver metabolizes midazolam?

A

alcohol increases clearance

cyt P450 inhibitors will decrease metabolism/increase free drug

decreased blood flow/liver function in elderly will increase free drug

59
Q

midazolam: placenta

is there concern for giving midazolam to pregnant/possibly pregnant women?

A

midazolam is guilty by association with older teratogenic benzodiazepams.

when in doubt, give fentanyl instead

60
Q

benzodiazepines: anti-convulsants

treatment for:

1.

2.

A
  1. local anesthetic-induced seizures
  2. alcohol withdrawal induced delirium tremens
61
Q

benzodiazepines: anti-convulsants

Benzos vs. barbiturates

A

Benzos: upregulate inhibitory actions of GABA, suppressing excitatory action

Barbiturates: suppresses the entire CNS

62
Q

benzodiazepines: anti-convulsants

diazapem dose effective for lidocaine toxicity, DTs, and status epilepticus

A

Diazepam 0.1mg/kg IV

63
Q

potency: midazolam vs. diazepam (valium)

A

midazolam 2-3X more potent than diazepam

64
Q

pK diazepam

A

6.15

65
Q

pharmacodynamics: midazolam

what makes midazolam so preferable?

1.

2.

3.

4.

A
  1. rapid onset
  2. short duration
  3. water soluble in solution
  4. lipid soluble in circulation
66
Q

drawbacks of diazepam (valium) and lorazepam (ativan)

1.

2.

A
  1. thrombophlebitis and venous irritation
  2. water insoluble/ burns

(because of water insolubity, diazepam and lorazepam must be suspended in propylene glycol – same ingredient in etomidate – burns)

67
Q

pros: diazepam and lorazepam

1.

2.

A
  • well absorbed in GI tract (great PO drug)
  • peak plasma levels in 1-2hr
68
Q

metabolism: diazepam and lorazepam

1.

2.

3.

A
  1. contraindicated for pts with renal disease (active metabolites)
  2. slow onset
  3. long elimination
69
Q

benzodiazepines to treat insomnia

1.

2.

A
  1. oxazepam
  2. flurazepam
70
Q

rohypnol

A

flunitrazepam

71
Q

xanax

A

alprazolam

72
Q

ambien

A

zolpidem

73
Q

reversal of benzodiazepines

A

flumazenil

74
Q

pharmacokinetics/pharmacodynamics: flumazenil

1.

2.

3.

A

short duration of action = resedation (redose)

metabolized in liver (no active metabolites)

excreted in kidneys

75
Q

benzodiazepine reversal

drug/dose

A

flumazenil

0.1-0.2mg IV repeated up to 3mg

ANESTHESIA PHARM 1 (4 decks)

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