Chp 15 IV Anesthetics Flashcards
MOA etomidate?
Imidazole compound - appears to depress CNS function via GABA
- Appears to increase number of GABA receptors, possibly displacing endogenous inhibitors of GABA binding
MOA propofol?
CNS effects via modulation of GABA-activated Cl channel
Specific site of action appears to be distinct from those of barbiturates, steroids, benzos, and GABA
GABA
Most common inhibitory neurotransmitter in mammalian nervous system
GABA receptor
Oligomeric complex consisting of:
- GABA R
- Assoc chloride ion channel
- Barbiturate receptor
- Benzo receptor
- picrotoxin binding site
Barbiturates
- Modulate GABA transmission
- Decreases rate of dissociation of GABA from R —> prolongs duration of GABA-induced opening of the chloride channel
- Especially capable of depressing activity in the reticular formation whose activity is necessary to maintain wakefulness
GABA = ?
Gamma-aminobutyric acid
Other features of barbiturates
- Selectively depress transmission at sympathetic ganglia —> may contribute to decreased BP following their administration
- High doses reduce sensitivity of postsynaptic membranes of NMJ to Ach thereby interfering with transmission
MOA GABA
Activation of postsynaptic GABA R increases chloride conductance through Cl ion channel —> hyperpolarization —> inhibition of the postsynaptic neuron
How to reverse benzos?
Flumazenil - pure benzodiazepine R antagonist
Which drugs reduce ICP?
Etomidate, propofol, thiopental
- Reduce ICP secondary to decreased cerebral metabolic consumption of oxygen and decreased cerebral blood flow
Which drugs increase ICP?
Ketamine, tiletamine increase cerebral blood flow, ICP, and cerebral metabolism
Which benzodiazepines are used in veterinary medicine?
Diazepam
Midazolam
Zolazepam (only avail in combo with tiletamine ie Telazol)
Midazolam vs diazepam
Midazolam more potent, water soluble
Shorter half life
Similar in effects to diazepam
Zolazepam
Water-soluble benzo
Available only in combination with tiletamine
Pharmacokinetics similar to those of diazepam, midazolam
Produces less tranquilization than diazepam or midazolam
At higher doses, can induce dysphoria and excitement
Do barbiturates have adverse effects on other organ systems?
- No direct effects on either liver or kidney function —> not nephrotoxic, hepatotoxic
- Alterations in liver, kidney function associated with their use secondary to hemo dynamic effects of the drugs and altered perfusion
- Placental transfer occurs rapidly —> when used at proper induction doses, excessive depression of the fetus does not occur
MOA ketamine
MOA not truly established
- appears the cyclohexamines exert effects via antagonism of CNS muscarinic ACh receptors, agonism of opioid receptors
- Specific NMDA ANTAGONIST
- blockade of adrenergic, serotonergic receptors attenuate ketamine-induced analgesia
NMDA?
N-methyl-D-aspartate glutamate
Function of NMDA
Principle excitatory receptor system in the mammalian brain
How ketamine available
Racemic mixture
- positive isomer: produces more intense analgesia, more rapid recovery, lower incidence of emergence reactions than the negative isomer
- both isomers appear to have cocaine-like effect in that they inhibit catecholamines into postganglionic sympathetic nerves
Properties of an ideal anesthestic
- Water soluble
- Long shelf life (>1yr)
- Stable on exposure to light
- Require small volume for anesthetic induction
- Safe/wide therapeutic index
- Rapid onset of action (one circulation time)
- Short duration of action
- Inactivated by rapid metabolism to nontoxic metabolites
- Not induce anaphylaxis or histamine release
- Nontoxic, nonirritating, no SE (only producing primary CNS effects)
Properties of barbiturates
- Dose-dependent state of sedation, hypnosis
- Drug levels persist for several hours even with ultrashort-acting drugs administered to induce GA
- Species differences in pharmacokinetics responsible for significant variation in duration of action among species
Which barbiturates are used in GA?
- Thiopental
- Methohexital
- Pentobarbital
- Thiobutabarbital (Inactin)
Recovery from barbiturates
- Single dose of thiopental, methohexital - redistribution of the drug from brain to non-nervous tissue (viscera, skeletal m)
- Methohexital: rapid hepatic metabolism as well
- Redistribution of pentobarb occurs but recovery primary due to metabolism
- Ultimate elimination of barbiturates by the body is by metabolsim: <1% recovered unchanged in the urine
Repeated exposure to barbiturates
-Results in tolerance due to induction of hepatic enzymes