Injectable anesthesia (Shih)

Question 1

Therapeutic index

Answer 1

(Lethal dose 50)/(Effective dose50)

High therapeutic index

• safer
• larger margin of safety

Question 2

Therapeutic index

1. Etomidate
2. Ketamine
3. Alfaxalone
4. Propofol
5. Thiopental

Answer 2

1. Etomidate: 16
2. Ketamine: High (double digits)
3. Alfaxalone: >20
4. Propofol: 3
5. Thiopental: 5

Question 3

Compartment theory

Answer 3

Redistribution

• drug leaving brain and going elsewhere
• doesn’t equal elimination

Question 4

Time of awakening is dependent on

Answer 4

Redistribution rate, not elimination rate

Question 5

12 bottles of beer adventure (hangover…?) due to

Answer 5

Elimination

Question 6

Continuous infusion

Answer 6

Can lead to accumulation of drug

Rate of decay depends on elimination rate not distribution

Question 7

Context Sensitive half life:

Answer 7

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

Question 8

Bolus vs Continuous infusion

(eg propofol vs thiopental)

When will a patient wake up?

Answer 8

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

Question 9

Barbiturate

MOA

Answer 9

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

Question 10

Thiopental

Answer 10

Good at shutting down brown (barbiturate coma)

CNS

• Dec CBF and CMRO2
• One of the best drugs to prevent high ICP

Question 11

Advantage of Tiopental

Answer 11

Short lasting barbituric

Awakening due to redistribution

Long half life/long context sensitive half life

• No recommended repeated bolus

Question 12

Thiopental

Metabolism

Answer 12

Metabolism

• Liver P450 dependent
• Careful on patients with low hepatic function (shunt)

Question 13

Propofol

Answer 13

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

Question 14

Propofol

MOA

Answer 14

GABA

• Same as thiopentol
• Cl in cell, none in blood

Question 15

Propofol

Advantage

Answer 15

Metabolism

• Fast clearance
• Extra hepatic metabolism
  
  • Use on Portosystemic shunt dogs (PSS)

Question 16

Propofol

Complications

Answer 16

Mayonnaise recipe

• Dont give in pancreatitis patients
  
  • maybe 1 bolus ok

Vehicle:

• Soy bean oil, egg lecithin
• Bacterial growth
• Fat embolisation
• High plasma triglyceride

Question 17

Propofol complications

Long-term use

Use in cats

Answer 17

Phenolic compound = oxidative injury

Heinz body and methemoglobinemia

Diarrhea/anorexia and malaise in cats

*In cats:

• 1 bolus probs ok
• CRI probs not ok

Question 18

1. Thiopental think:
2. Propofol think:
3. Etomidate think:

Answer 18

1. Thiopental: Brain
2. Propofol: Liver
3. Etomidate: Heart

Question 19

Etomidate

Answer 19

TI (therapeutic index) = 16

Cardiovascular stability: good

• even in hypovolemia

Minimal respiratory depression

Decreased intracranial pressure

Decreased cerebral oxygen consumption

Question 20

Etomidate

Disadvantage

Answer 20

Poorly water soluble

Formulated in 35% propylene glycol

High osmolality

• may cause phlebitis IV admin

Question 21

Etomidate

adverse events

Answer 21

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)

Question 22

Etomidate best for:

Answer 22

1. Heart murmur patients

• Yorkie w/ mitral regurge
• Dobie w/ DCM
• Cat w/ HCM

Question 23

Ketamine (Relax)

Answer 23

Classified as a dissociative anesthetic

• Not complete anesthesia

Limbic and thalamocortical systems are dissociated: alters awareness

Cortex and medulla don’t communicate

Question 24

Ketamine about

Answer 24

Bad recovery

• Use with xylazine in horses

Schedule III

• huge abuse potential

Question 25

Ketamine Pharmacokinetics/metabolism

Answer 25

Lipid soluble * can give IM Highly protein bound * low protein goes straight to brain

Question 26

Ketamine MOA

Answer 26

Non-competitive NMDA receptor antagonist * only anesthetic with analgesic properties Some additional

Question 27

Ketamine Physiologic effects

Answer 27

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

Question 28

Ketamine is the ONLY injectible anesthetic that...

Answer 28

Provides some analgesia Give SQ

Question 29

Telazol (Zoletil)

Answer 29

Tiletamine + zolazepam (same thing as ketamine + diazepam) FDA schedule III Dissociative Bad recovery Muscle tension Inc CO NMDA receptors

Question 30

Alfaxalone

Answer 30

Advertised as ideal anesthetic * Therapeutic index low * Doesn't cause histamine release * Can give IM * No respiratory depression * water soluble Vehicle: cyclodextrin encapsulation

Question 31

Alfaxolone MOA

Answer 31

Gaba

Question 32

Alfaxolone Physiologic effects

Answer 32

High therapuetic index Inc in Heart rate * Good for heart Decrease in BP * Good for BP Good for lungs Good muscle relaxation **No analgesia**

Question 33

Summary and conclusions

Answer 33

Therapuetic index Distribution vs Elimination Accumulation vs CRI