Premedication and sedation Flashcards by Josie Campbell

Goals of pre-medication and sedation

To tranquilise the patient

To decrease the doses of anaesthetic agents used for induction and maintenance of anaesthesia

To facilitate a smooth and stress free recovery

Pre-emptive analgesia-good for invasive procedures

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Classes of drugs used for premed/sedation

Phenothiazines - ACP

Alpha 2 adrenoreceptor agonists - medetomidine, dexmedetomidine, xylazine, romifidine, detomidine

Benzodiazepines - midazolam, diazepam, zolazepam

Opioid analgesics - methadone, butorphanol, buprenorphine

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What class of drug is acepromazine (ACP)?

Phenothiazine

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What class of drugs includes medetomidine, dexmedetomidine, xylazine, romifidine, detomidine?

Alpha 2 adrenoreceptor agonists

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What class of drugs includes Midazolam, diazepam, zolazepam?

Benzodiazepines

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What class of drugs includes methadone, morphine, butorphanol, buprenorphine?

Opioids

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Liccenced premed/sedation drugs for dogs

Medetomidine
Dexmedetomidine
Xylazine

Mathadone
Buprenorphine
Butorphanol
Fentanyl

Zolazepam (in Zoletil)

Acepromazine

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Liccenced premed/sedation drugs for cats

Medetomidine
Dexmedetomidine
Xylazine

Methadone
Buprenorphine
Butorphanol
Fentanyl
(Pethidine)

Zolazepam (in zoletil)

Acepromazine

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Liccenced premed/sedation drugs for horses

Xylazine
Dexmedetomidine
Romifidine

(Butorphanol)

Acepromazine

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Liccenced premed/sedation drugs for cattle

Xylazine
(Romifidine)

(Acepromazine)

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Liccenced premed/sedation drugs for pigs

(Acepromazine)
Azaperone

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MoA of Acepromazine

Blockade of the dopaminergic receptors D2

Antagonism of the a1 adrenergic receptors

Blockade of histaminic receptors (serotoninergic pathway)

Blockade of the muscarinic receptors

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Pros of Acepromazine

Long acting tranquiliser (smoother recovery)

Reliable sedation in dogs (aggressive dogs can still wake up and be aggressive)

Some anti-arrhythmic properties (less relevant these days)

Cheap and licensed for many animals (protects against possible legal issues)

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Cons of Acepromazine

No analgesia (not a big deal if combined with analgesics)

Vasodilation and hypotension (blocks peripheral a1 receptors)

Unreliable in cats

Poorly reliable to sedate aggressive animals

Long lasting effects (up to 6-7 hours)

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Which types of patients can Acepromazine be used in?

All healthy, young dogs

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When should Acepromazine be avoided or used with caution?

In cases of:

○ Uncorrected hypovolaemia/hypotension

○ Severe renal disease

○ HCM/ left ventricular hypertrophy

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MoA of Alpha-2 adrenoreceptor agonists

Stimulation of alpha2 (negative feedback) pre-synaptic adrenergic receptors in the brain and spinal cord, which causes a decrease in noradrenergic activity.

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Side effects of Alpha-2 adrenoreceptor agonists

Bradyarrhythmia’s (receptors are on the vasculature, the heart etc.)

Stimulation of the alpha1 receptors (vasoconstriction)- could increase blood pressure

More alpha2 selective molecules may cause less vasoconstriction

Central cardiovascular depression owing to decreased adrenergic output (central so bradycardia may not resolve even with vasoconstriction)

Increase in blood glucose levels (stimulation of alpha1 receptors) so need to be careful with diabetes patients but otherwise not too clinically relevant

Respiratory depression

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Selectivity of Alpha-2 adrenoreceptor agonists

Dexmedetomidine (highest selectivity)

Medetomidine

Romifidine

Detomidine

Xylazine (lowest selectivity)

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Pros of Alpha-2 adrenoreceptor agonists

Good analgesia (spinal)

Reliable sedation in dogs, cats, and equine

Reliable in a variety of animal species

Antagonizable

Short acting (1 hour)

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Cons of Alpha-2 adrenoreceptor agonists

Arrhythmogenic

Increase (most common)/decrease in BP

Cardiac and respiratory depression

Moderately expensive (but agent-dependent)

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Which patients can Alpha-2 adrenoreceptor agonists be used in?

Healthy, young dogs as premedication or to sedate for short ambulatory procedures

Aggressive dogs and cats for IM sedation

Many non-conventional species (rabbits, rats, wild and selvatic animals)

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When should you avoid Alpha-2 adrenoreceptor agonists or use them with caution?

Severe cardio-respiratory disease/impairment

Diabetic patients

In general, sick animals classified as ASA III

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MoA of benzodiazepines

Binding of GABAa receptors in the brain and spinal cord, which enhances the effects of GABA (inhibitory neurotransmitter)

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Pros of benzodiazepines

Cardiovascular and resp functions are minimally affected Myorelaxation Tranquilisation in neonates, geriatric, or very sick dogs and cats Anticonvulsant properties

Cons of benzodiazepines

Unreliable as sedative agents in most dogs and cats Behavioural excitatory reactions are common (might see hallucinations in cats) Antagonists are expensive Myorelaxation may result in decrease respiratory function

Which patients can have benzodiazepines?

Neonates (less than 4 weeks) Geriatric or very sick dogs and cats In patients with increased risk of seizures In case of severe cardiac impairment When myorelaxation is desirable (e.g. Fractures)

When should you avoid the use of benzodiazepines, or use them with caution?

Healthy young, non-premedicated animals Hepatic encephalopathy

Which animals do of benzodiazepines have good sedative effects in?

○ Pigs ○ Primates ○ Ferrets ○ Rabbits ○ Birds

MoA of opioids

Action through various ion channels of both pre- and post- synaptic neuronal membranes, which leads to hyperpolarization of the post-synaptic axon and interruption of nociceptive pathways in the brain and spinal cord Different types of receptors µ, δ and κ Mimic endogenous opioids

Endogenous opioids

Endorphins Dysnorphins Enkephalins

Exogenous opioids

Drugs Powerful analgesic Treatment of moderate to severe pain

Opioid receptors

µ: powerful analgesia but also side effect κ: dysphoria, less potent analgesia

Common side effects of opioids

Sedation (desired or undesired) Resp depression Bradycardia Dysphoria/excitement Spontaneous locomotor activity Changes in pupil size (mydriasis in cats and horses, variable in dogs) Vomiting Decreased gut motility Urinary retention

Duration of effects of morphine

2-4hrs

Is morphine licensed?

Receptoral binding of morphine

Potent µ-agonist

Special features of morphine use

Vomiting and histamine release

Duration of effect of methadone

Up to 4hr

Is methadone licensed?

Yes (cats and dogs)

Receptoral binding of methadone

µ-agonist

Special features of methadone use

Hyperventilation possible

Duration of effect of pethidine

1-2hr

Is pethidine licensed?

Yes - for cats

Receptoral binding of pethidine

µ-agonist

Special features of pethidine use

Histamine release (IM!)

Duration of effect of fentanyl

10-15mins

Is fentanyl licensed?

Yes (cats and dogs)

Receptoral binding of fentanyl

Potent µ-agonist

Special features of fentanyl use

Suitable for CRI

Duration of action of butorphanol

1-2hr

Is butorphanol licensed?

Yes (cats and dogs)

Receptoral binding of burtorphanol

µ- antagonist and κ- agonist

Special features of butorphanol use

Poor analgesic

Duration of action of buprenorphine

6-7hrs

Is buprenorphine licensed?

Yes (cats and dogs)

Receptoral binding of buprenorphine

Weak µ-agonist

Special features of buprenorhine use

Useful for post-op analgesia

Morphine

Gold standard, pure µ-agonist potent opioid Potential histamine release, vomiting Duration: 2-4 hours Not licensed in animals Schedule 2

Methadone

Pure µ-agonist opioid No histamine release if given IV Duration: up to 4 hours Licensed for dogs and cats Schedule 2

Butorphanol

Κ-agonist and µ-antagonist (mild sedative, poor analgesic) Used in combination with sedative drugs for minimally invasive procedures Duration: 1-2 hour Licensed for dogs and cats Not listed as controlled drug in the UK

Buprenorphine

Weak µ-agonist: not as potent as morphine (but better than butorphanol) Duration: up to 7 hours Licensed for dogs and cats Schedule 3 (less controlled than morphine) Often preferred in practice for its long duration and fewer side effects

Pethidine

µ-agonist of short duration (1 hour) Histamine release: must be given IM Other mechanisms of action (atropine-like, blockade of Na+ channels) Licensed for cats Schedule 2

Fentanyl

Very potent µ-agonist, short acting opioid Used as an infusion Licensed for dogs and cats Schedule 2

Naloxone

Opioid antagonist - to treat opioid overdose or in crash situation

Which patients can opioids be used for?

All the patients in pain or undergoing invasive surgeries As sedatives in patients with cardiac diseases

When should opioids be used with caution?

Resp impairment (as sedatives) Allergic conditions, asthma (morphine and pethidine)- can be used but cant be left unattended

Sedation/premed protocols

Opioid, ACP, benzodiazepine or alpha2-agonist alone Drugs of the same classes are not combined Opioid and ACP Opioid and alpha2-agonist Opioid and benzodiazepine

What does a medetomidine and methadone combination produce?

A sleepy dog, happy to be held

ACP and methadone combination

very good drug combination but take different amounts of time to work, first methadone (A few minutes, little change or more excitement and panting) then acepromazine (after 20mins more sleepy and calm, no panting)