Benzodiazepines Flashcards
1
Q
sustained state of apprehension and autonomic arousal in response to real or perceived threats
A
anxiety
2
Q
FEAR OF SUFFERING AND DEATH, LOSS OF CONTROL, AND FRUSTRATION caused by the inability to communicate
A
anxiety
3
Q
headache, insomnia, nausea, anorexia, dyspnea, palpitations, dizziness, dry mouth, chest pain
A
symptoms: anxiety
4
Q
diaphoresis (excessive sweating), hyperventilation, tachycardia, etc.
A
signs: anxiety
5
Q
onset: midazolam
A
30-60sec
6
Q
peak: midazolam
A
3-5min
7
Q
duration: midazolam
A
15-80min
8
Q
postoperative benzodiazepine
A
lorazepam (Ativan)
9
Q
onset: lorazepam
A
1-2min
10
Q
peak: lorazepam
A
20-30min
11
Q
duration: lorazepam
A
6-10hr
12
Q
preoperative PO benzodiazepine
A
diazepam
13
Q
elimination half-time: midazolam
A
1.9hr
14
Q
elimination half-time: diazepam (Valium)
A
43hr
15
Q
elimination half-time: lorazepam
A
14hr
16
Q
comprise a category of drugs widely used in anesthesia as anxiolytics, sedatives, and hypnotics
A
benzodiazepines
17
Q
benzodiazepines: site of action
A
GABAA (gamma-aminobutyric acid) receptors
18
Q
most lipid soluble (in vivo) clinical benzodiazepine
A
midazolam
19
Q
benzodiazepines: mechanism of action
1.
2.
A
- Hyperpolarization of cell (facilitate opening of GABA-activated Cl- channels, increase of inhibitory effect at the CNS side)
- Receptor occupancy determines effect
(anxiolysis < sedation < unconsiousness)
20
Q
where are GABAA receptors found in the highest density?
A
CEREBRAL CORTEX
21
Q
20% GABA receptor occupancy: effect
A
anxiolysis
22
Q
30-50% GABA receptor occupancy: effect
A
sedation
23
Q
60% GABA receptor occupancy: effect
A
unconsiousness
24
Q
effects: GABA receptor agonism by clinical use of bendiazepines
1.
2.
3.
4.
A
- sedation/hynosis
- anxiolysis
- anticonvulsant (seizures – epilectic, alcohol withdrawal, etc.)
- ANTEROGRADE amnesia
25
NOT effects of benzodiazepines
1.
2.
3.
4.
1. analgesic effects
2. antidepressant
3. antipsychotic
4. protect against stress of intubation (again, no analgesic effect; will still see sympathetic response to stimuli)
26
midazolam: pediatric preoperative dosage
0.5mg/kg PO 30min before
| (15mg max)
27
midazolam: IV sedation (ICU sedation) dosage
0.5-4mg IV load then 1-7mg/hr IV
28
midazolam: IV induction of anesthesia dosage
0.1-0.2mg/kg
29
diazepam: supression of seizure activity dosage
0.1mg/kg
30
Midazolam: pharmacokinetics
ABSORPTION
1.
2.
3.
31
midazolam: more or less for acute intoxication
less (GABA receptors already activated)
32
midazolam: more or less for chronic alchoholic
more (tolerance)
33
benzo given for alchohol withdrawal
Ativan (lorazepam)
34
GABA receptor addiction issues
barbituates (bind to GABA receptors similar to benzos)
35
treatment for local anesthetic induced seizures and alcholism detoxification-related seizures
Ativan (lorazepam)
36
mechanism of seizures due to detoxification (alcoholism)
withdrawal of agonist from GABA receptors, thus excitatory reaction instead of inhibitory action when ligand is no longer activating
37
midazolam: component of balanced anesthetic
how much can you reduce MAC requirements by administering midazolam preoperatively?
as much as 30%
38
midazolam: pediatrics
what juice can you not mix midazolam with?
grapefruit juice
will trigger an exaggerated effect
39
midazolam: cross tolerance
what drugs should alert you that pt may have higher tolerance to midazolam?
Xanax, Ambien, other benzos
heavy alcohol use/abuse
40
midazolam: pharmacokinetics
PO (pediatrics)
50% first pass metabolism
41
Pharmacokinetics: distribution
highly lipid soluble benzodiazepines
(really fast onset times)
midazolam, lorazepam
ambien
42
how does lipid solubility affect how ambien is prescribed?
ambien has high lipid solubility, therefore fast onset time.
prescribed for those that have trouble falling asleep
43
how does lipid solubility affect how lunesta is prescribed?
lunest has low lipid solubility, therefore slow onset time.
lunesta is prescribed for those that have trouble falling asleep
44
midazolam pharmacokinetics: distribution
describe the mechanism that affects how long midazolam works
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
midazolam pharmacokinetics: distribution
volume of distribution in elderly and obese
Vd is high for elderly and obese, therefore has longer duration of action
46
midazolam pharmacokinetics: protein binding
what percent of protein binding do benzodiazepines exhibit?
90-98%
47
midazolam pharmacokinetics: protein binding
describe how hypoalbumenia/ decreased liver function affects midazolam pharmacodynamics
hypoalbumenia = decreased albumin
decreased protein binding
increased free drug available
EXAGGERATED EFFECT
48
midazolam: metabolism
pathway for metabolism
liver oxidation (cytochrome P450)
any drug that inhibits cyt P450 will cause benzos to hang around longer
49
midazolam: metabolism
how does alcohol affect clearance?
alcohol INCREASES clearance of benzos
50
midazolam: metabolism
metabolites?
no active metabolites for midazolam
51
midazolam: metabolism
how does metabolism relate to dysphoria/cognitive disfunction in elderly?
decreased blood flow, decreased kidney/liver function/flow = decreased metabolism = more free drug available
also, increased Vd = longer duration
52
midazolam: elimination
ESRD – reason to worry?
no. although metabolites excreted in urine, metabolites are inactive, thus no real concern.
53
midazolam: central nervous system
how does midazolam affect cerebral metabolic oxygen requirements (CMRO2) and cerebral blood flow?
decreased CMRO2
decreased CBF, therefore, decreased risk of high ICP
54
midazolam: CNS
EEG?
no isoelectric EEG
55
midazolam: CNS
neuroprotection?
no evidence of neuroprotection
56
midazolam: ventilation
describe concern for synergistic effects of midazolam with fentanyl
midazolam has dose dependent decrease in respiration. synergism with (high doses of) fentanyl can induce apnea
57
midazolam: cardiovascular
how does midazolam affect bp and hr?
MINOR decrease in bp, increase in hr
58
midazolam: liver
how do drugs and age affect how the liver metabolizes midazolam?
alcohol increases clearance
cyt P450 inhibitors will decrease metabolism/increase free drug
decreased blood flow/liver function in elderly will increase free drug
59
midazolam: placenta
is there concern for giving midazolam to pregnant/possibly pregnant women?
midazolam is guilty by association with older teratogenic benzodiazepams.
when in doubt, give fentanyl instead
60
benzodiazepines: anti-convulsants
treatment for:
1.
2.
1. local anesthetic-induced seizures
2. alcohol withdrawal induced delirium tremens
61
benzodiazepines: anti-convulsants
Benzos vs. barbiturates
Benzos: upregulate inhibitory actions of GABA, suppressing excitatory action
Barbiturates: suppresses the entire CNS
62
benzodiazepines: anti-convulsants
diazapem dose effective for lidocaine toxicity, DTs, and status epilepticus
Diazepam 0.1mg/kg IV
63
potency: midazolam vs. diazepam (valium)
midazolam 2-3X more potent than diazepam
64
pK diazepam
6.15
65
pharmacodynamics: midazolam
what makes midazolam so preferable?
1.
2.
3.
4.
1. rapid onset
2. short duration
3. water soluble in solution
4. lipid soluble in circulation
66
drawbacks of diazepam (valium) and lorazepam (ativan)
1.
2.
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
pros: diazepam and lorazepam
1.
2.
* well absorbed in GI tract (great PO drug)
* peak plasma levels in 1-2hr
68
metabolism: diazepam and lorazepam
1.
2.
3.
1. contraindicated for pts with renal disease (active metabolites)
2. slow onset
3. long elimination
69
benzodiazepines to treat insomnia
1.
2.
1. oxazepam
2. flurazepam
70
rohypnol
flunitrazepam
71
xanax
alprazolam
72
ambien
zolpidem
73
reversal of benzodiazepines
flumazenil
74
pharmacokinetics/pharmacodynamics: flumazenil
1.
2.
3.
short duration of action = resedation (redose)
metabolized in liver (no active metabolites)
excreted in kidneys
75
benzodiazepine reversal
drug/dose
flumazenil
0.1-0.2mg IV repeated up to 3mg
