Sedation and premedication Flashcards
Define premedication
Administration of medication prior to anaesthesia:
- facilitate/improve peri-anaesthetic period
- long acting drugs may span the whole period
- animals should be maintained under observation
Aims of premed
Reduce anxiety Facilitate handling Peri-operative analgesia Facilitate smooth anaesthetic induction, maintenance and recovery Reduce dose (anaesthetics) Reduce risks of specific complications
Why are anti-cholinergics used a premeds?
Less commonly nowadays but to reduce secretions. Also: used when there was:
- increased vagal tone
- vagomimetic drugs (opioids)
- ressuscitation
- adjuncts to antagonism of mm blockers
Major effects - anticholinergics - 5
Increased HR Bronchodilation Decreased secretions (more viscous) Mydriasis Reduced GIT motility
2 examples - anti-cholinergics
ATROPINE: crosses BBB (remember rabbits have atropine esterase)
GLYCOPYRROLATE: lower magnitude increase in HR (than atropine), longer acting (1 hour), not licensed in animals
Define anxiolytic
calming effect, less interest in environment, still aroused by stimuli, AKA tranquilisers/nebulisers (not same but often used interchangeably)
Define sedative
calming effect, less responsive to stimuli, sleepiness, may also be analgesics
Define narcosis
drug-induced sleep, not easily aroused
Define hypnosis
artificially-induced sleep, broader meaning
List the 5 classes of sedatives
Phenothiazines Butyrophenones Benzodiazepines Alpha-2 adrenergic agonists (opioids?)
Describe phenothiazines
Highly protien bound (>90%) Lipophilic (cross placenta and BBB) Hydrophilic (IM absorption) Hepatic metabolism Excretion - urine and bile
Effects - Phenothiazines -8
CALMING - main reason for use, blocks CNS dopamine-R
POTENTIATE CNS DEPRESSION (of other drugs): opioids, anaesthetics
EXTRAPYRAMIDAL EFFECTS - high doses
PERIPHERAL VASODILATION: blocks alpha-1 adrenergic receptors
ANTI-EMETIC EFFECT: inhibits CRTZ
ANTI-HISTAMINE EFFECTS: blocks H1 receptor
ANTI-MUSCARINIC EFFECTS: antispasmodic in GIT
HYPOTHERMIA: depression of thermoregulatory centre, increased vasodilation –> heat loss
List 3 examples of phenothiazines
ACEPROMAZINE (ACP)
PROMETHAZINE
CHLORPROMAZINE
Which phenothiazine is the only phenothiazine licensed in animals?
Acepromazine (ACP)
When is promethazine used?
ACTIONS:
anti-histamine
For nausea, vomiting, motion sickness (human)
Advantages - acepromazine -3
- Anxiolytic (low dose) OR sedative (higher dose)
- Anti-arrhythmic: reduce SNS activity, membrane stabilising effects (LA effect), blockade of cardiac alpha adrenergic receptors
- PO administration - variable absorption
Disadvantages - acepromazine - 12
HYPOTENSION - blocks alpha 1 adrenergic receptors, suppresses SNS
SYNCOPE - due to hypotension and bradycardia, brachycephalics more susceptible (naturally high vagal tone and upper airway obstruction)
CARDIAC SPHINCTER RELAXATION: anti-muscarinic effect –> increases risk of reflux and regurgitation
DECREASED PCV and TS - due to splenic sequestration OR vasodilation causing an increased intravascular space volume with consequent RBC dilution
LATE ONSET OF ACTION
LARGER ANIMALS MORE SENSITIVE
CONCOMITANT USE OF ADRENALINE - ACP blocks alpha1 receptors –> vasodilation. Adrenaline may lead to unopposed beta2 activity –> vasodilation.
(SEIZURE THRESHOLD - reduced)
ANTI-THROMBOTIC - due to decreased platelet count, inhibit aggregation, transien
AVOID USE PRIOR TO INTRADERMAL SKIN TESTING
MAY POTENTIATE EFFECTS OF ORGANOPHOSPHATES
RELAXATION OF RETRACTOR PENIS MUSCLE IN HORSES
When should you avoid acepromazine?
Age extremes (BP regulation problems) Renal/hepatic disease Hypovolaemia/most shock states Brachycephalics Breeding stallions
Where do BUTYROPHENONES work?
Same receptors as Phenothiazines - but degree of localisation on specific receptors is variable. They have a sedative action due to dopamine antagonism. Also has anti-emetic properties and causes vasodilation and hypotension.
When are butyrophenones used?
Pigs, healthy animals
Sedation and behavioue modification
Pharmacodynamics - azaperone
Peak sedation in 15-30 mins (IM)
Sedation duration 2-3 hours
Decrease HR, CO, ABP
Impaired thermoregulation
What is the metabolism/excretion of azaperone?
Hepatic metabolism –> inactive metabolites
Renal excretion
What class of sedatives does azaperone belong to?
Butyrophenones
What can azaperone be combined with?
Ketamine –> immobilisation, anaesthesia
Opioids: for painful diagnostic or minor surgical procedures
Define neuroleptoanalgesia
a state of quiescence, altered awareness and analgesia produced by a combination of an opioid analgesic and a neuroleptic
List 2 examples of neuroleptoanalgesic mixtures
HYPNORM: fluanisone and fentanyl
INNOVAR VET: droperidol and fentanyl
IMMOBILON: acepromzaine and etorphine, extremely potent, immobilisation of large wild animals
Are benzodiazepines licensed for vet use in the UK?
No
List 3 commonly used benzodiazepines
Diazepam
Midazolam
(Zolazepam)
How do benzodiazepines work?
Act of GABA-A receptor: allosteric modulation, increased affinity/active of GABA therefore increased inhibitory NT conductance.
Main actions - benzodiazepines - 4
Anticonvulsant
Anxiolytic/sedative
Skeletal mm relaxation (minor)
Amnesiac (anterograde)
Define anterograde amnesia
= loss of the ability to create new memories after the event that caused the amnesia, leading to a partial or complete inability to recall the recent past, while long-term memories from before the event remain intact.
Define retrograde amnesia
memories created prior to the event are lost while new memories can still be created
T/F: anterograde and retrograde amnesia can occur together in the same patient
True
Side effects - benzodiazepines - 4
Few side effects:
Minimal CVS and resp. depression
Induction of liver enzymes
Possibility of a paradoxical response
Define paradoxical response
Where a sedative is given and excitement is seen instead of sedation in a small % of animals
What is Flumazenil an example of?
A benzodiazepine
Outline flumazenil action
Rapid onset of action (5 mins)
Short elimination 1/2 life - dogs
May facilitate seizures in predisposed animals
List uses of benzodiazepines - 7
Convulsions/status epilepticus (not HE)
Anxiolytic/sedative
Muscle relaxation (tetanus, urolithiasis)
With opioids (induction, enhance sedation)
With ketamine
Co-induction
Behaviour modifying
Outline use and administration of diazepam
PO, IV, rectal/intracloacal (IM absorption less predictable)
USE: Appetite stimulation (Cats)
List the 2 injectable formulations of diazepam
Propylene glycol and Intralipid (milder)
Describe midazolam
Twice as potent as Diazepam
Shorter acting
PO, IM (water-soluble), IV, intranasal/transmucosal
Metabolites not v active - suitable for infusion
Define tautomer
they are isomers of a compound which differ only in the position of protons and electrons
Where are alpha-2 receptors found?
located centrally and peripherally. Pre, post and extrasynaptic lcations
Pharmacokinetics - alpha2 adrenoceptor agonists
High lipophilicty –> crosses BBB, placenta and MM with ease.
Hepatic metabolism
Renal excretion
Effects - alpha 2 agonists
SEDATION: duration dose dependent, synergistic with opioids, able to arouse momentarily - caution!, beware stressed patients, CRI
ANAESTHETIC SPARING (50-70%!, IV - slow administration, CRI)
NEUROPROTECTIVE - prevents neuronal death, vasocontriction may help reduce ICP.
ANALGESIA - mostly visceral, some superficial, LA properties (xylazine)
What is meant when an animal is ‘flat’?
When it is sedated.
Side effects - alpha 2 agonists - 8
CVS - 3 STAGES: initial HYPERTENSION (peripheral vasconstriction and stimulation of vascular alpha 2 adrenoceptors) –> BRADYCARDIA ( reflex, central sympatholysis,) –> HYPOTENSION. Also makes MM pale or cyanotic. Can be PRO-ARRHYTHMIC
RESPIRATORY: RR reduced, MV maintained, careful of oedema in small ruminants
ENDOCRINE: diuresis due to decreased ADH production and responsiveness, insulin resistance (-> hyperglycaemia), interference with RAAS
GENITO-URINARY: may increased uterine tone, vasoconstriction (placenta)
GIT: reduced mortality and BF, LOS tone reduced –> emesis.
THERMOREGULATION: reduced central heat production, decreased heat loss
HAEMATOLOGICAL: decreased PCV and TS, enhanced platelet aggregation
OPTHALMALOGICAL: decreased IOP
List some examples of alpha2 -adrenoceptor agonists - 5
Xylazine Detomidine Romifidine Medetomidine Dexmedetomidine
Outline xylazine
First alpha-2 agonist for vet med License - dog, cat, horse, cattle Species sensitivity: ruminants>horse/dog/cat>pig Causes emesis (cats) Short half-life
Outline Detomidine
License - horses, cattle
IV, IM and transmucosal (horse)
Longer action than xylazine
Outline Romifidine
License -horse
Similar profile as Detomidine
Produces less ataxia
Outline medetomidine and dexmedetomidine
Medetomidine - 2 isomers - dexmedetomidine is one of them, essentially v similar actions
License - dog, cats but used in many other species
‘Cleaner’ drugs in the group
How can you reverse the sedative and CV effects of analgesia?
Antagonism using one of the following: Tolazoline Yohimbine Atipamezole Atipamezole
OVERDOSE MAY CAUSE EXCITEMENT
Describe atipamezole
Most selective alpha 2 antagonist available
Most suitable for ‘newer alpha 2 agonists
Cats - more sensitive
Dose adjusted according to time/drugs
Administered IM
