Types of premedication

Question 1

What different drug classes are used for premed?

Answer 1

• opioids
• alpha-2 agonists
• phenothiazines
• benzodiazepines
• NMDA receptor antagonists
• anticholinergics
• alfaxalone

Question 2

Examples of opioids

Answer 2

• methadone
• fentanyl
• pethidine
• morphine
• buprenorphine
• butorphanol

Question 3

Benefits of using opioids

Answer 3

• provides sedation and analgesia
• generally cause minimal cardiovascular depression
• often used in very sick pts
• respiratory depression is usually minimal at clinical doses

Question 4

Is morphine licenced in veterinary species?

Answer 4

• no

Question 5

Cons of using opioids

Answer 5

• some vagally mediated bradycardia can be seen at high doses
• respiratory depression can be seen with fentanyl or high doses of methadone given IV
  – if give these peri-operatively can cause apnoea
• they reduce GI motility and decrease gastric emptying
• morphine can induce emesis

Question 6

Which 4 receptor types do opioids act on?

Answer 6

• mu
• kappa
• delta
• nociceptin

Question 7

Opioid reversal/antagonist

Answer 7

• naloxone

Question 8

Which opioids have the best analgesic effects?

Answer 8

• full mu agonists
  – methadone
  – fentanyl
  – pethidine
  – morphine

Question 9

Which opioids are moderate analgesics?

Answer 9

• partial mu agonists
  – buprenorphine

Question 10

Which opioids provide good sedation but relatively poor and short-lived analgesia?

Answer 10

• butorphanol
  – mu antagonist and kappa agonist

Question 11

Which opioid is good for birds and why?

Answer 11

• butorphanol
• birds have a high proportion of kappa receptors

Question 12

Examples of alpha-2 agonists

Answer 12

• medetomidine
• dexmedetomidine
• xylazine
• detomidine
• romifidine

Question 13

Which alpha-2 agonists are most commonly used in SA practice?

Answer 13

• medetomidine
• dexmedetomidine

Question 14

Why is xylazine less commonly used in SA practice?

Answer 14

• poor affinity for the alpha-2 receptor (cf. medetomidine & dexmedetomidine)
• therefore significantly more side effects

Question 15

Is xylazine licenced in horses and cattle?

Answer 15

• yes

Question 16

Is Detomidine licenced in horses and cattle?

Answer 16

• yes

Question 17

Which species is romifidine licenced in?

Answer 17

• horses/equids only

Question 18

Benefits of alpha-2 agonists

Answer 18

• profound dose dependent sedation
  – therefore can be useful in very lively or aggressive animals at higher doses
• marked drug sparing effects
  – reduce MAC, therefore reduce amount of inhalation required and amount of induction agent
• good analgesics
• cause minimal respiratory depression
• good muscle relaxant

Question 19

Cons of alpha-2 agonists

Answer 19

• increase the amount of time it takes for injectable anaesthetics to travel to the CNS so care re injecting too quickly if already given alpha-2 agonists
• reduce blood flow to the liver and reduce hepatic metabolism of other agents
• analgesia is relatively short lived
• be cautious of the degree of sedation caused in brachy breeds as there’s potential for URT obstruction
• significant cardiovascular effects
  – associated with marked bradycardia / hypotension
  – not used in sick pts or those with CV dz
• can cause emesis
  – particularly in cats if used alone
• reduce endogenous insulin production
  – therefore result in transient hyperglycaemia
• urine production is increased
  – as the result of reduced renin and vasopressor secretion
• analgesic effect shorter than sedative

Question 20

What are the cardiovascular effects of alpha-2 agonists

Answer 20

• biphasic
• initially peripheral vasoconstriction results in an increase in bp
• in response there’s a reflex bradycardia and reduction in cardiac output
• after ~15-20 mins bp and hr return to normal

Question 21

Alpha-2 agonist reversal/antagonist

Answer 21

• atipamezole

Question 22

What is the only phenothiazine licenced for veterinary use?

Answer 22

• acepromazine (ACP)

Question 23

What can ACP be combined with as part of a premed?

Answer 23

• opioid +/- alpha-2 agonist

Question 24

Benefits of phenothiazines

Answer 24

• contributes to sedation/tranquilisation
• provides anxiolysis
• lasts ~6-8h in healthy animals
• respiratory depression is minimal in healthy animals
• considered anti-arrhythmic due to effects of alpha-1 receptor antagonism in the heart, cell membrane stabilisation and sympathetic tone reduction, but the clinical effects of this are unknown

Question 25

Cons of phenothiazines

Answer 25

- no analgesic properties - slow to taking effect -- ~30-40mins when administered IM - vasodilation caused by alpha-1 antagonism can result in hypotension and hypothermia - cannot be reversed/antagonised - effects on vasodilation can be hard to manage - not suitable for pts with sepsis, hypovolaemia, CV compromise - reports of syncope in boxers - giant breeds are considered more susceptible to the CV effects of ACP - duration of action may be significantly prolonged in some sight hounds (24h) - dogs with MDR1 mutations may be more sensitive - priapism reported in horses -- but risk of permanent penile dysfunction is low - oral absorption can be erratic and unpredictable, hence IM or IV preferable - rapid distribution and will cross BBB and placenta

Question 26

Where do phenothiazines act?

Answer 26

- centrally acting by antagonising D1&D2 receptors, also acts on alpha-1 muscarinic and H1 receptors

Question 27

Examples of benzodiazepines

Answer 27

- diazepam - midazolam

Question 28

Which benzodiazepine is licenced in horses?

Answer 28

- midazolam

Question 29

Which benzodiazepine in licenced in dogs and cats?

Answer 29

- diazepam

Question 30

Why can the available formation of diazepam only be given IV?

Answer 30

- cause pain IM and are poorly absorbed

Question 31

How can midazolam be administered?

Answer 31

- IM - IV

Question 32

How do benzodiazepines act?

Answer 32

- centrally acting via the GABA-A receptor

Question 33

Benefits of benzodiazepines

Answer 33

- anxiolytic - sedative - causes hyponosis - minimal CV and respiratory depression -- therefore potentially good for sick/compromised pts e.g. in combination with an opioid or ketamine - reduce the amount of induction and inhalation agent - in sick pts midzolam can be used as a co-induction agent rather than as a part of premed - contribute to muscle relaxation - cause amnesia in people so may do this for our spp - anticonvulsant - high lipid solubility aiding oral and IM absorption - widely distributed in body with rapid central activity

Question 34

Cons of benzodiazepines

Answer 34

- not analgesic - degree of sedation in healthy animals is often poor and can result in disinhibition, esp if given IV -- these pts may become aggressive -- therefore, not given normally to a healthy pt as part of premed

Question 35

Benzodiazepine reversal/antagonist

Answer 35

- flumazenil -- competes for the receptor without producing effects -- but is short-lived and doses may need to be repeated -- expensive and probably isn't available in most 1st opinion practices

Question 36

Example of NMDA receptor antagonist

Answer 36

- ketamine - methadone and pethidine are opioids which also demonstrate some NMDA receptor antagonism

Question 37

Benefits of ketamine

Answer 37

- at high doses ket is a dissociative anaesthetic and appears to interrupt association pathways to the brain and results in sensory blockade -- Depresses the thalamoocortical system and activates the limbic system - At lower doses results in sedation and at even lower doses can be used e,g, in an infusion for analgesia - profoundly reduces the amount of induction agent and inhalation anaesthetics - good cardiovascular stability and is stimulatory or a sympatheticomimmetic i.e. stimulation is by noradrenaline release - it causes a transient increase in cardiac output and blood pressure - extreme lipid solubility ensures its rapid transfer across BBB

Question 38

Cons of ketamine

Answer 38

- in some sick patients administration has caused a reduction in blood pressure probably due to myocardial depression in the presence of altered sympathetic tone (?catecholamine depletion). - therefore in theory some animal might not be able to cope with the stimulation produced by higher (i.e. anaesthetic doses) - results in variable dose dependent respiratory depression, although this is probably not of huge concern at subanaesthetic doses - relatively short acting (30-45 minutes) due to high hepatic clearance - when used alone it’s a poor muscle relaxant - drying to the corneas - ome patients who have received higher doses can be excitable/ very reactive to light/ noise/movement on recovery, but this is usually manageable +/- a sedative

Question 39

Examples of anti-cholinergics

Answer 39

- atropine - glycopyrrolate

Question 40

Benefits of anti-cholinergics

Answer 40

- reduce bradycardia and are sometimes used intraoperatively in response to alpha-2s - reduce the amount of respiratory tract secretions and are therefore sometimes added into a premed in circumstances where this is a potential concern e.g. brachy animal undergoing respiratory surgery

Question 41

Cons of anti-cholinergics

Answer 41

- not routinely used in premed and do have unwanted effects -- mydriasis (pupil dilation), reduced gut motility, bronchodilation etc

Question 42

What is aflaxalone?

Answer 42

- a neuroactive steroid

Question 43

When is alfaxalone used for pre-med?

Answer 43

- can be used to sedate sick pts, e.g. in combination with an opioid when ket is not a good option - occasionally given IM to pts where a robust premed hasn't provided sufficient sedation to place an IV cannula

Question 44

Cons of alfaxalone

Answer 44

- mild vasodilation when given IV, but this is unlikely to occur IM - apnoea has been reported when given IV

Question 45

Benefits of alfaxalone

Answer 45

- few adverse effects on the CV system - cardiac output and tissue perfusion are maintained with its use - apnoea is not reported when administered IM