Injectable anesthesia (Shih) Flashcards
Therapeutic index
(Lethal dose 50)/(Effective dose50)
High therapeutic index
- safer
- larger margin of safety
Therapeutic index
- Etomidate
- Ketamine
- Alfaxalone
- Propofol
- Thiopental
- Etomidate: 16
- Ketamine: High (double digits)
- Alfaxalone: >20
- Propofol: 3
- Thiopental: 5
Compartment theory
Redistribution
- drug leaving brain and going elsewhere
- doesn’t equal elimination
Time of awakening is dependent on
Redistribution rate, not elimination rate
12 bottles of beer adventure (hangover…?) due to
Elimination
Continuous infusion
Can lead to accumulation of drug
Rate of decay depends on elimination rate not distribution
Context Sensitive half life:
Time it takes to wake up once a CRI is discontinued
Time necessary for plasma drug concentration to dec by 50% after d/c ing a continuous infusion of a specific duration
Bolus vs Continuous infusion
(eg propofol vs thiopental)
When will a patient wake up?
If given a bolus, patient will wake up at the same time with either drug
- due to redistribution
If given an infusion, patient given propofol will wake up sooner
- better elimination
- Bigger hangover with thiopental
Barbiturate
MOA
Lethal injection
Mechanism of action
- Interaction with Gamma amino butyric acid (GABA) receptor
- Cl- hyperpolarizes cells, goes in and makes cell sleep
Tiopentol and Diazepam
Thiopental
Good at shutting down brown (barbiturate coma)
CNS
- Dec CBF and CMRO2
- One of the best drugs to prevent high ICP
Advantage of Tiopental
Short lasting barbituric
Awakening due to redistribution
Long half life/long context sensitive half life
- No recommended repeated bolus
Thiopental
Metabolism
Metabolism
- Liver P450 dependent
- Careful on patients with low hepatic function (shunt)
Propofol
Side effect:
- Respiratory depression
- Cardiovascular depression (dec CO)
- usually short lived
- Don’t use unless you have a captured airway
Short acting/fast clearance
Bolus
- Recovery due to redistribution
Smooth induction and recovery
Short context sensitive half life
CRI
- wakes up from elimination
- wake up quickly
Propofol
MOA
GABA
- Same as thiopentol
- Cl in cell, none in blood
Propofol
Advantage
Metabolism
- Fast clearance
- Extra hepatic metabolism
- Use on Portosystemic shunt dogs (PSS)
Propofol
Complications
Mayonnaise recipe
- Dont give in pancreatitis patients
- maybe 1 bolus ok
Vehicle:
- Soy bean oil, egg lecithin
- Bacterial growth
- Fat embolisation
- High plasma triglyceride
Propofol complications
Long-term use
Use in cats
Phenolic compound = oxidative injury
Heinz body and methemoglobinemia
Diarrhea/anorexia and malaise in cats
*In cats:
- 1 bolus probs ok
- CRI probs not ok
- Thiopental think:
- Propofol think:
- Etomidate think:
- Thiopental: Brain
- Propofol: Liver
- Etomidate: Heart
Etomidate
TI (therapeutic index) = 16
Cardiovascular stability: good
- even in hypovolemia
Minimal respiratory depression
Decreased intracranial pressure
Decreased cerebral oxygen consumption
Etomidate
Disadvantage
Poorly water soluble
Formulated in 35% propylene glycol
High osmolality
- may cause phlebitis IV admin
Etomidate
adverse events
Endocrine
- shuts down adrenal glands
- no cortisol
- no corticosteroids
- no aldosterone
- Short term supression NBD
- Long-term supression = inc mortality
- Don’t give to stressed patients (ICU)
Etomidate best for:
- Heart murmur patients
- Yorkie w/ mitral regurge
- Dobie w/ DCM
- Cat w/ HCM
Ketamine (Relax)
Classified as a dissociative anesthetic
- Not complete anesthesia
Limbic and thalamocortical systems are dissociated: alters awareness
Cortex and medulla don’t communicate
Ketamine about
Bad recovery
- Use with xylazine in horses
Schedule III
- huge abuse potential
Ketamine Pharmacokinetics/metabolism
Lipid soluble
- can give IM
Highly protein bound
- low protein goes straight to brain
Ketamine
MOA
Non-competitive NMDA receptor antagonist
- only anesthetic with analgesic properties
Some additional
Ketamine
Physiologic effects
Direct myocardial depressant
- In patients with no sympathetic tone
In patients with sympathetic tone
- inc cardiac output
- inc blood pressure
- inc heart rate
Increased muscle tone
- use with muscle relaxants
- diazepam
- dexmetatomadine
Ketamine is the ONLY injectible anesthetic that…
Provides some analgesia
Give SQ
Telazol (Zoletil)
Tiletamine + zolazepam (same thing as ketamine + diazepam)
FDA schedule III
Dissociative
Bad recovery
Muscle tension
Inc CO
NMDA receptors
Alfaxalone
Advertised as ideal anesthetic
- Therapeutic index low
- Doesn’t cause histamine release
- Can give IM
- No respiratory depression
- water soluble
Vehicle: cyclodextrin encapsulation
Alfaxolone
MOA
Gaba
Alfaxolone
Physiologic effects
High therapuetic index
Inc in Heart rate
- Good for heart
Decrease in BP
- Good for BP
Good for lungs
Good muscle relaxation
No analgesia
Summary and conclusions
Therapuetic index
Distribution vs Elimination
Accumulation vs CRI
