Ch.18: Injectable Anesthesia Pharm (Shih) Flashcards
therapeutic index
lethal dose50/effective dose50. High therapeutic index is better
rank therapeutic indices of propofol, ketamine, thiopental, etomidate, alfaxalone**
ketamine > alfaxalone (>20) > etomidate (16)»_space; thiopental (5)> propofol (3)
Compartment theory
drugs have 3 main compartments that they go into: blood, high blood-flow organs (brain), and low-flow organs (fat, muscle, tendon, skin).
-Drug gets quickly redistributed from brain into GI, where it is eliminated slowly
elimination half-life
time for plasma conc. of drug to drop by 50%
elimination half-time
time for plasma conc. of drug to drop by 50% during elimination phase
time of awakening is dependent on:**
redistribution rate, NOT elimination rate. If 2 drugs causing sedation are elimated at different rates, time of awakening will still be the same because they are being redistributed at the same rate
how many half-times before drug can be considered effectively cleared from system?*
4
loading dose =
vol of distribution X target plasma conc.
vol of distribution =
total dose/drug plasma conc.
continuous infusion
- a repeated bolus
- “little sips throughout the night”
- can lead to drug accumulation
- rate of decay depends on elim. rate
- CRI
CRI =
continuous rate infusion
context sensitive half life**
time necessary for the plasma drug conc. to decrease by 50% after discontinuing a CRI of a specific duration
barbiturates in general have low/high therapeutic index
low
barbiturates mech. of action**
interact with GABA receptor to open Cl channels and promote CNS depression
Can Cl channel be opened without GABA?*
yes (explains why some animals will sleep if given thiopentane)
thiopental fx
- shuts down brain and lowers O2 requirement of the brain
- prevents ICP buildup
thiopental chars.
- short lasting barbituric
- awakening due to redistr.
- long half life
thiopental metabolism
liver. Don’t use in patients with low hepatic fx (i.e. portal shunt!)
thiopental disadvantages**
- expensive
- skin irritant (it is very basic)
- sight hounds have prolonged and agitated recovery. (drug can build up in blood instead of fat since they have low fat)**
propofol has low/high therapeutic index**
low
propofol chars/advantages**
- short acting/fast clearance
- recovery due to redistr.
- smooth induction/recovery
- short half life
- extra hepatic metabolism, so good for patients with liver problems such as PSS
- vasodilator
propofol disadvantages**
- resp/CV depression (usually short-lived)
- drops BP
- oily vehicle can induce bacterial growth, fat embolism, high plasma triglyceride**
- long-term use can result in oxidative injury, Heinz body form, MetHb, diarrhea/anorexia/malaise in cats
indications for propofol
C-sections
etomidate has low/high therapeutic index**
high
Etomidate chars/desired effects**
- doesn’t adversely affect CV stability
- minimal resp. depression
- dec. intracranial P
- dec. cerebral oxygen consumption
- poorly lipid soluble
vehicle of etomidate
propylene glycol
problems with propylene glycol
- pain on inject
- hemolysis
- can cause hyperosmolar state
adverse effects of etomidate**
- ADRENAL SUPPRESSION: inhibits 11-beta-hydroxylase, which converts cholesterol to glucocorticoids and mineralocorticoids. results in decreased cortisol, corticosterone, aldosterone.
- Do NOT give if animal is sick or stressed
Is ketamine controlled drug?
YES
Ketamine is classified as:
- dissociative anesthetic (awareness altered)
- non-competitive NMDA receptor antagonist
Which is more potent: ketamine-S or R in racemic mixture?**
S
Is ketamine lipid soluble? Protein bound?
Yes very much so for both
Ketamine absorption
- good IV or IM absorption
- transmucosal
ketamine metabolism
- hepatic
- norketamine active metabolite
ketamine mech. of action**
- non-competitive NMDA receptor antagonist
- prevents glutamate from binding NMDA
- depresses activity in thalamocortical, limbic, and reticular activating system
- also acts at opioid and muscarinic receptors
- can be used as infusion
ketamine effects
- myocardial depressant (??)
- inc. sympathetic tone (inc. cardiac output/BP/HR/muscle tone)
why is ketamine used with diazepam?
to counteract muscle rigidity caused by ketamine
How is ketamine unique among injectable agents?**
provides some analgesia, even at low doses
can give telazol IV?
yes
telazol = combo of:
tiletamine + zolazepam
Alfaxalone chars.
- not yet available in US
- water soluble
- IV or IM
- doesn’t cause histamine release
- high therapeutic index
- can be used as an infusion
Alfaxalone controlled?
NO
vehicle for alfaxalone**
cyclodextrin encapsulation (a protein)
alfaxalone mech. of action
enhances GABA
alfaxalone effects
- dec. BP
- inc. HR
- depressed resp.
- muscle relaxation
alfaxalone provide analgesia?
no
alfaxalone metabolism
-hepatic via glucuronidation
see table from whiteboard
:)
