GA: Injectable Anaesthetic Agents

Question 1

When do we use injectable anaesthetic agents?

Answer 1

• Induction of anaesthesia before administration of an inhalational agent (usually IV).
• Adjunct to inhalational anaesthesia (“balanced anaesthesia technique”).
• Short term anaesthesia (usually IM).
• Total intravenous anaesthesia (TIVA).

Question 2

1. How do you triple?
2. How do you quad?

Answer 2

1. Opioid, a2 agonist, ketamine.
2. Opioid, a2 agonist, ketamine and BZD.

Question 3

1. What are the injectable anaesthetic agents which have UK marketing authorisations for administration to animals?
2. Which are most used in SA practice?
3. Which is most used in equine practice?
4. Which is least commonly used?

Answer 3

1. Propofol – Dogs, cats.
   Alfaxalone – Digs, cats, pet rabbits.
   Ketamine – Horses, dogs, cats.
   Tiletamine / zolazepam – dogs, cats.
2. Propofol, alfaxalone.
3. Ketamine.
4. Tiletamine / zolazepam.

Question 4

1. Action of propofol, alfaxalone and barbiturates.
2. Action of ketamine. – what also works in this way?
3. What type of drug is zolazepam? – what is its action?

Answer 4

1. GABA agonists.
   Enhance inhibitory NT GABA w/in CNS.
2. NMDA antagonist. – Tiletamine portion of Tiletamine/zolazepam also works in this way.
3. BZD – GABA agonist.

Question 5

Drugs used for euth.

Answer 5

• Pentobarbital.
• Secobarbital Sodium (quinalbarbital sodium) plus Cincocaine Hydrochloride = Somulose for cats, dogs, horses, cattle.

Question 6

How do euth drugs work?

Answer 6

Barbiturate enhances actions of GABA receptor.
Local anaesthetic acts to block sodium channels and this will cause blockade of that, interrupting cardiac AP.

Question 7

What are factors that affect the effects of drugs?

Answer 7

• Blood flow to the brain.
• Amount of non-ionised drug – only non-ionised drug can cross BBB.
• Lipid solubility – BBB = lipid bilayer so lipid-soluble drugs cross BBB easier.
• Molecular size.
• Concentration gradient.
• Protein binding – Proportion that bind to plasma proteins will not exert effect.
• Distribution – influences how long they last.
• Metabolism – influences how long they last (many but not all by liver).
• Excretion (many but not all by kidneys).

Question 8

What are qualities that make the ideal injectable anaesthetic agent?

Answer 8

• Rapid onset of action.
• Non irritant.
• Minimal cardiopulmonary effects.
• Rapidly metabolised and eliminated.
• Non-cumulative.
• Good analgesia.
• Good muscle relaxation.

Question 9

Route of drug when injected IV.

Answer 9

Through vein.
Reaches R side of heart.
Through lungs.
Reaches L side of heart.
Into arterial system.
To brain.

Question 10

1. Why would we want it to be non-irritant?
2. Why would we want it to be non-cumulative?

Answer 10

1. So can be injected IM w/ no negative response, or IV in case any drug is delivered perivascular.
2. So it can be topped up or dosed again.

Question 11

1. How does propofol meet criteria?
2. What is action of propofol?
3. Why do you have to be careful with propofol dosing in hypoalbuminemic animals?
4. How can dose be given carefully?

Answer 11

1. Rapid onset of action.
   Lipid soluble.
   Rapidly metabolised and eliminated.
   Non-cumulative in dogs.
   Fair muscle relaxation.
   Non-irritant.
2. GABA agonist.
3. Propofol highly plasma protein bound so less albumin means more unbound propofol available for binding with receptors.
4. Titrate the drug in slowly to effect – adequate but not overdose.

Question 12

1. How does the metabolism of propofol differ between cats and dogs?
2. How is the metabolism of propofol in dogs and cats similar?
3. What can occur resp-wise after induction? – How can incidence of this be reduced?
4. What occurs circulatory-wise and by what mechanisms?

Answer 12

1. Cats lack glucuronidation pathway w/in liver so can accumulate in cats if given by repeated dosing.
2. Both hepatically metabolise it. Both also have evidence of extra-hepatic metabolism so may be good agent to use in animals with hepatic dysfunction.
3. Post-induction apnoea – Give drug slowly.
4. Hypotension by myocardial depression and peripheral vasodilation.

Question 13

1. Does propofol have analgesic effects?
2. Muscle relaxation?
3. What has been reported in cats when propofol used? (haem). – why?
4. In what form is propofol presented? – How is this a negative? – Guidance? – Recently brought in in UK?

Answer 13

1. no.
2. Fair and adequate but may see twitching and rarely muscle rigidity after induction of anaesthesia.
3. Heinz body anaemia. – oxidative damage to RBCs with consecutive day use over prolonged period (5-7 days).
4. In an egg protein and lipid emulsion – supports bacterial growth. – withdraw volume needed and discard rest. – Propofol containing preservatives.

Question 14

1. What preservative is in propofol preparation?
2. How long can this preserved propofol be stored for?
3. Use for prolonged infusion?

Answer 14

1. Benzyl alcohol.
2. 28 days.
3. Do not use for prolonged infusion.

Question 15

1. What type of anaesthetic is alfaxalone?
2. At what receptor does alfaxalone act?
3. What is alfaxalone solubilised in? – why? – Describe the solution.

Answer 15

1. Steroid anaesthetic.
2. GABA receptor.
3. Cyclodextrin solution – not water soluble. – Ring sugar molecule which has hydrophilic exterior and lipophilic interior. Alfaxalone molecule sits in the centre of this ring, enabling the non water soluble molecule to be water soluble.

Question 16

1. How does Alfaxalone meet criteria?
2. How does hypoalbuminemia have less of an impact on dose required when using alfaxalone compared to propofol?
3. Alfaxalone respiratory/circulatory effects.

Answer 16

1. Non-irritant (? IM) (Licensed for IV in UK) (Licensed for IM in Australia).
   Rapid onset.
   Rapid metabolism (liver) and elimination.
   Non cumulative.
2. Only 20% plasma protein bound.
3. Some respiratory depression.
   Preserves baroreceptor tone – HR increases in response to reduced BP (may see transient tachycardia after anaesthesia induction).

Question 17

1. What type of anaesthetic is ketamine?
2. Where does ketamine act?
3. Muscle relaxation?

Answer 17

1. Dissociative anaesthetic.
2. NMDA antagonist.
3. Poor – not used as sole agent (w/ BZD or a2 agonist).
   Reflexes maintained (central eye, palpebral reflex, may swallow).
   Sympathetic stimulation – release of adrenaline.

Question 18

1. Onset of action of ketamine?
2. How does ketamine meet criteria?
3. Metabolism and excretion?
4. Plasma protein binding?
5. Use of ketamine in vet med?
6. CV effects?

Answer 18

1. Slow – so need quiet environment.
2. Maintains CV / respiratory function.
   Analgesic/antihyperalgesic.
   Non cumulative though has active metabolite – nor-ketamine (can prolong duration of action).
3. Metabolism by liver, excretion by kidneys (can be compromised in animals w/ renal dysfunction).
4. ~50%.
5. Most commonly induction and TIVA for maintenance of anaesthesia by IV (w/ guaifenesin and a2 agonist).
   Cats IM – sedation as well as induction of anaesthesia (Part of triple and quad techniques).
6. May increase IOP/ICP – use cautiously in animals with certain ophthalmic conditions and neurological disease.

Question 19

1. Trade name of Tiletamine / Zolazepam on EU – and North America?
2. UK marketing authorisation for what spp in UK?
3. Tiletamine / Zolazepam route of administration.
   4, What is the cause of some poor quality recoveries from this drug combination in dogs?

Answer 19

1. Zoletil – Tilosol.
2. Dogs and cats, not rabbits.
3. IM or IV.
4. Zolazepam metabolised much more quickly than the Tiletamine – Repeated dosing not recommended.

Question 20

1. What drug type is thiopental?
2. Where does thiopental act?
3. What occurs w/ accidental perivascular administration of thiopental? – why?
4. How does thiopental meet criteria?

Answer 20

1. Barbiturate.
2. GABA receptors.
3. Tissue necrosis – very alkaline solution.
4. Rapid onset.

Question 21

1. Thiopental plasma protein binding?
2. Thiopental recovery?
3. CV and respiratory effects.
4. What is the reason for prolonged recovery after repeated dosing?
5. Big advantage of thiopental?

Answer 21

1. 80%.
2. Primarily through redistribution of drug to tissues and then hepatic metabolism.
   Prolonged in sighthounds compared to other breeds – was thought to be due to low body fat meaning less tissue for drug redistribution, and low body fat causing higher susceptibility to hypothermia. But now found that there is a difference in metabolic pathways for thiopental in sighthounds compared to other breeds.
3. Moderate cardiorespiratory depression – ventricular bigeminy.
4. Thiopental is cumulative.
5. Very predictable effect – especially in horses.

Question 22

Factors that may affect elimination of an IV anaesthetic agent and thus recovery from anaesthesia.

Answer 22

• Drug factors incl. dose.
• Spp, breed, age (PK diffs).
• Co-morbidities.
• Neuro function.
• CV function (agent distribution around body and delivery to kidneys).
• Hepatic function (many agents metabolised by the liver).
• Renal function (many agents excreted by kidneys).
• Hypothermia (alters hepatic metabolism as slows down process, also alters renal plasma flow).
• Additional factors such as concurrent drug administration.

Question 23

When may TIVA be useful?

Answer 23

• To reduce exposure to inhalant. e.g. bronchoscopy.
• In the field. (no access to specialist anaesthetic machines).
• Specific conditions. e.g. some specialist neurosurgical procedures where IV anaesthetic agents may confer some benefits.

Question 24

1. Ideal properties of drugs used for TIVA.
2. What does CRI stand for?

Answer 24

1. • Rapid metabolism and elimination.
     - Fast onset of action.
     - High therapeutic index.
     - Pharmacokinetics available – so infusion rates can be calculated.
2. Constant Rate Infusion.

Question 25

1. What agent would you choose when performing bronchoscopy in cats?
2. Why?
3. What agent would you use for TIVA in dogs?
4. What agent would you use for TIVA in a horse in the field?

Answer 25

1. Alfaxalone.
2. Non cumulative in cats.
   Fast onset of action.
   Relatively high therapeutic index.
   PK available for cats and dogs – published on data sheet.
3. Alfaxalone or propofol.
4. Ketamine + BZD for induction then maintain anaesthesia w/ triple drip – combo of ketamine, guaifenesin and a2 adrenal receptor agonist.
   (Ketamine is fairly rapidly metabolised and eliminated but does not meet ideal property of a fast onset, but does have high therapeutic index and PK available for horses and TIVA doses are well established).