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Cognition & Senses - wk 3 > benzodiazepines > Flashcards

benzodiazepines Flashcards

1
Q

what are the pharmacologic effects

A
  • anxiolysis
  • sedation
  • anticonvulsive effects
  • spinal cord mediated muscle relaxants
  • anterograde amnesia
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2
Q

pharmacologic effects in vet med

A
  • prevent muscle rigidity associated with ketamine
  • synergistic effect with other drugs (anethesia, opioids, inhalant)
  • first line drug for treating acute onset of seizure
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3
Q

what are the type of receptors

A

GABAa receptors only

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4
Q

mechanism of action

A
  • facilitates binding of GABA to the receptor - enhance the affinity of the receptor for GABA
  • increases Cl- conductance
  • hyperpolarization of post synaptic membrane
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5
Q

benzodiasepines are adjacent ____ and ____ subunits on the GABA receptor

A

a and y

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6
Q

GABAa subunit importance

A
  • a1 responsible for sedative effects
  • a2/3 responsible for anxiolytic effects
  • accounds to different effects in different species
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7
Q

excitement

A

some species (dog/cat) if used alone - excitatory phase than sedation if used alone IV & cats possibility of excitement if used in premed

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8
Q

why excitement with benzodiazepines

A
  • small vs large animals
  • age difference
  • pharmacodynapic possibilities
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9
Q

high lipophilicity

A
  • rapid onset of action and faster redistribution = shorter duration
  • lipophilicity (midazolam>diazepam>lorazepam)
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10
Q

pharmacokinetics

A
  • large volume of distribution
  • high protein binding (albumin)
  • clearance differs between benzodiazepines
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11
Q

how does awakening occur

A

comes from redistribution of drug from brain to other less perfused tissues

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12
Q

CNS effects

A
  • decrease CMRO2 and CBF (protective against cerebral hypoxia)
  • increases seizure threshold of local anesthetics
  • midazolam does not produce isolectric EEG (increases ICP when given rapidly IV and slow administration is recom.)
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13
Q

respiratory depression

A
  • midazolam>diazepam=lorazeopam
  • esp. if midazolam is given fast IV
  • decrease in tidal volume
  • flatten CO2 dose response curves
  • additive effects with opioids
  • reversed with surgical stimulation
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14
Q

cardio-vascular effects

A
  • cardiovascular stability
  • some reduction in blood pressure (midazolam more than diazepam, synergistic effects with other anesthetic drugs)
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15
Q

is diazepam soluble in water

A
  • no - insoluble in water; viscous solution
  • dilution with sterile water or saline
  • injection may be painful IV
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16
Q

what method of administration is diazepam not recommended for

A

IM - should give slowly IV

17
Q

what is the formulation of diazepam

A

propylene glycol formulation

18
Q

diazepam metabolism

A
  • metabolized hepatic microsomial oxidation
  • decreases hepatic biotransformation

easier for liver to metabolize midazolam than diazepam)

19
Q

diazepam clinical pharmacology

A
  • less reliable sedation vet med (arousal dogs, excitement, aggression in cats)
  • ataxia, recumbency in horses
20
Q

midazolam

A
  • water-soluble
  • 2-3 times more potent than diazepam
  • 2-3 times the affinity for the GABAa receptor
21
Q

why midazolam can be used IM

A
  • midazolam changes chemical structures at different pH
  • in bottle pH 3.5 benzene ring open (water-soluble, good IM absorption/non-irritating)
  • once in blood pH increases and at pH>4 benzene ring closes (more lipid soluble than diazepam, fast onset - easily crosses BBB)
22
Q

midazolam metabolism

A
  • short duration of action
  • rapid redistribution from the brain to inactive tissues
  • hydroxylation by hepatic and small intestinal microsomial oxidative mechanism)
23
Q

midazolam clinical uses

A
  • most common in human med
  • convenient in exotic species (IM)
  • close less than diazepam
24
Q

flumazentil is a competitive ____ at GABAa receptor

A

antagonist

25
Q

flumazentil affinity

A

high affinity for receptors

26
Q

flumazenil agonist activity

A

minimal (high doses)

27
Q

flumazenil structure and solubility

A
  • similar structure to midazolam
  • weak water solubility
  • moderate lipid solubility
28
Q

flumazenil clearance and metabolism

A
  • rapid plasma clearance
  • metabolized by liver
29
Q

flumazenil is a reversal for:

A

benzodiazepines

  • reverses sedation, respiratory depression
  • no cardiovascular effects
30
Q

flumazenil duration

A
  • dose depentant
  • depends on type and dose of agonist used

Cognition & Senses - wk 3 (13 decks)

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