9a – Induction and Injectable Anesthetics

Question 1

Injectable anesthetics: mechanism of action is via

Answer 1

• Potentiation or facilitation of GABA by their actions at GABAa receptors in the CNS
• *need a high concentration of drug to rapidly reach the site of action (THE BRAIN) for a titratable effect

Question 2

Properties of an ideal injectable drugs

Answer 2

• Rapid onset of action
• Smooth induction and recovery
• Non-irritant
• Good bioavailability by ALL routes
• Short duration of action
• Non-cumulative
• Rapid metabolism
• No toxic or histamine release
• Minimal cardiorespiratory side effects
• Degree of muscle relaxation and analgesia
• Stable in storage and solution
• Miscible with other agents
• Inexpensive
• High therapeutic index (SAFE!)

Question 3

Advantages of injectable drugs

Answer 3

• Little equipment needed
• Usually easy to administer
• Induction can be rapid and smooth
• Possibly cheaper
• No environmental pollution

Question 4

Disadvantages of injectable drugs

Answer 4

• Once give, retrieval is IMPOSSIBLE
• Need accurate weight to calculate dose
• Not well tolerated in all patients
• Some have potential for human abuse
• Risk of inadvertent self-administration

Question 5

Disadvantage of injectable drugs when used as a sole anesthetic agent

Answer 5

• High doses necessary to produce sufficient CNS depression to prevent response to surgical stimulus
• Profound CV and respiratory depression

Question 6

Injectable drugs not well tolerated by all patients

Answer 6

• Debilitated, hypovolemic or endotoxemia patients
• Patients suffering from renal or hepatic disease

Question 7

When do you use injectable anesthetics?

Answer 7

• Sedation: low doses can result in profound and reliable sedation (ex. ‘Ketamine stun’)
• Induction=MAIN USE (surgical plane to pass a endotracheal tube)
• Maintenance
• Emergency (supplement inhalation anesthesia if animal rapidly ‘wakes up’)

Question 8

Routes of administration for injectable drugs

Answer 8

• IM
• Subcutaneous/rectal/oral
• Intraperitoneal
• IV

Question 9

IM: injectable drugs

Answer 9

• Less precision
• Difficult to titrate effect
• Best for wildlife anesthesia

Question 10

Subcutaneous/rectal/oral: injectable drugs

Answer 10

• Too slow
• Unreliable

Question 11

Intraperitoneal: injectable drugs

Answer 11

• Risk of depositing drug in gut
• Laboratory animals

Question 12

IV: injectable drugs

Answer 12

• Accurate, titratable, rapid-acting
• *act in 20-60s: Rapidly achieves surgical plane (Stage 3)
• Bypasses stage 1 and 2 (excitement) with correct dose
• Requires restraint and ideally an IV catheter
• **PREFERRED route of administration if possible

Question 13

Pharmacokinetics of IV bolus injection: alpha phase

Answer 13

• DISTRIBUTION phase
• Distribution from blood to vessel-rich tissues
• Heart, brain, lungs, liver, kidneys
• Lipophilic=uptake into CNS is rapid

Question 14

Pharmacokinetics of IV bolus injection: beta phase

Answer 14

• ELIMINATION phase
• Elimination from central compartment (blood)
• Drug leaves CNS, goes back into blood and animal recovers from anesthetic effects
• Also have some redistribution (more into fat=quicker wake up and then excrete it)

Question 15

How drug movement influences anesthetic recovery

Answer 15

• IV injection into central compartment (highly vascular organs) then redistribution to less vascular (ex. fat) tissue, move into blood slowly
• metabolized and eliminated

Question 16

Modern injectable anesthetics that have an anesthetic effect lasting:

Answer 16

• 4-10 mins
• For longer procedures: more injectable drug is given (‘top-ups’) or switch to inhalation drugs

Question 17

Recovery from injectable bolus

Answer 17

• Initially: REDISTRIBUTION=drug from brain to blood and other body systems
• ‘hangover effect’=rapidly metabolized drugs produce little hang-over

Question 18

Anesthetic drugs (lipid soluble) metabolism and excretion

Answer 18

• Phase I: oxidation reduction, hydrolysis
• Phase II: conjugation
• *can produce ACTIVE metabolites

Question 19

Examples of ACTIVE metabolites

Answer 19

• Nordiazepam
• Morphine glucuronide

Question 20

Drugs metabolized in other sites as well as the liver

Answer 20

• *Propofol (ex. a patient with liver failure): kidney, lungs, guts
• *Remifentanil, Atracurium: plasma
• DURATION of action=short as they don’t need to go to the liver

Question 21

Constant rate infusion (CRI)

Answer 21

• Not changing rate

Question 22

Variable rate infusion (VRI)

Answer 22

• Changing rate

Question 23

IV infusion vs. bolus

Answer 23

• Give bolus and then use IV fusion
• *maintain plane better
• **infusions are nicer than boluses

Question 24

How do we administer these injectable drugs?

Answer 24

1. INDUCE anesthesia
2. To MAINTAIN anesthesia

Question 25

Induction goal

Answer 25

• Achieve stage 3 anesthesia and bypass the excitement phase

Question 26

Induction

Answer 26

• Consider physical status of patient
• Slow injection OR give 1/3 to ½ calculated dose
  o Wait for max effect
  o Proceed further with increments until desired effect

Question 27

Induction in small animals

Answer 27

• Titrate ‘to effect’
• Consider premedication (20-80% dose reduction depending on premedication)

Question 28

Induction in large animals

Answer 28

• Give whole dose
  o SAFETY! (do NOT want a partially anesthetized horse)

Question 29

Maintenance using injectable drugs options

Answer 29

• TIVA
• PIVA

Question 30

TIVA: total IV anesthesia

Answer 30

• One or more drugs can be used (multimodal)
• Can be slow to change depth of anesthesia

Question 31

PIVA: partial IV anesthesia

Answer 31

• Use injectable drugs to supplement inhalation anesthesia

Question 32

What are the different injectable anesthetics?

Answer 32

1. Substituted phenols (Propofol)
2. Neurosteroids (alfaxalone CD-RTU)
3. Phencyclidine derivative / Aryl-Cyclohexamines (dissociative) (Ketamine)