benzodiazepines Flashcards
what are the pharmacologic effects
- anxiolysis
- sedation
- anticonvulsive effects
- spinal cord mediated muscle relaxants
- anterograde amnesia
pharmacologic effects in vet med
- prevent muscle rigidity associated with ketamine
- synergistic effect with other drugs (anethesia, opioids, inhalant)
- first line drug for treating acute onset of seizure
what are the type of receptors
GABAa receptors only
mechanism of action
- facilitates binding of GABA to the receptor - enhance the affinity of the receptor for GABA
- increases Cl- conductance
- hyperpolarization of post synaptic membrane
benzodiasepines are adjacent ____ and ____ subunits on the GABA receptor
a and y
GABAa subunit importance
- a1 responsible for sedative effects
- a2/3 responsible for anxiolytic effects
- accounds to different effects in different species
excitement
some species (dog/cat) if used alone - excitatory phase than sedation if used alone IV & cats possibility of excitement if used in premed
why excitement with benzodiazepines
- small vs large animals
- age difference
- pharmacodynapic possibilities
high lipophilicity
- rapid onset of action and faster redistribution = shorter duration
- lipophilicity (midazolam>diazepam>lorazepam)
pharmacokinetics
- large volume of distribution
- high protein binding (albumin)
- clearance differs between benzodiazepines
how does awakening occur
comes from redistribution of drug from brain to other less perfused tissues
CNS effects
- 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.)
respiratory depression
- 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
cardio-vascular effects
- cardiovascular stability
- some reduction in blood pressure (midazolam more than diazepam, synergistic effects with other anesthetic drugs)
is diazepam soluble in water
- no - insoluble in water; viscous solution
- dilution with sterile water or saline
- injection may be painful IV
what method of administration is diazepam not recommended for
IM - should give slowly IV
what is the formulation of diazepam
propylene glycol formulation
diazepam metabolism
- metabolized hepatic microsomial oxidation
- decreases hepatic biotransformation
easier for liver to metabolize midazolam than diazepam)
diazepam clinical pharmacology
- less reliable sedation vet med (arousal dogs, excitement, aggression in cats)
- ataxia, recumbency in horses
midazolam
- water-soluble
- 2-3 times more potent than diazepam
- 2-3 times the affinity for the GABAa receptor
why midazolam can be used IM
- 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)
midazolam metabolism
- short duration of action
- rapid redistribution from the brain to inactive tissues
- hydroxylation by hepatic and small intestinal microsomial oxidative mechanism)
midazolam clinical uses
- most common in human med
- convenient in exotic species (IM)
- close less than diazepam
flumazentil is a competitive ____ at GABAa receptor
antagonist
