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GENERAL ANAESTHETICS (Alfaxalone (Effects (Dose dependent CVS depression,…

- - - - no histamine release
    - - rapid crossing of BBB
        
        rapid and smooth induction
        
        One injection site-brain circulation time
        
        rapid recovery
        
        less smooth than propofol :warning:
        
        appropriate pre-med involving sedative
        
        May get excitement without sedative
  - - - sulphate and glucoronide conjugates
    - - repeated doses possible
  - - - reduced systemic vascular resistance
        
        reduced stroke volume and cardiac output hypotension
      - transient compensating tachycardia :warning:
        
        Baroreceptor reflex is preserved
      - :red_cross: arrhythmogenic
      - :red_cross: sensitisation to catecholamines
    - - hypoventilation
      - dyspnoea
        
        Raise threshold of sensitivity to CO2
- - - - combined with ACP, alpha2 agoinistm opiods, benzodiazepines
    - - after alpha2 agonist
        
        induction/maintenance
    - - induction
    - - sedation/induction
  - - - painful if not via i/v :!!:
  - - - norketamine
      - Dihydronorketamine in horses
    - - no metabolism
        
        excretes active compound through kidneys
        
        Problem with large doses
  - - - produces unconsciousness (debatable)
      - maintains cranial and laryngeal reflexes
        
        Laryngeal
        
        Still does not prevent aspiration pneumonia
        
        Makes intubation more difficult
      - increased salivation
      - Dissociate noxious stimulus to the brain
        
        Still perceiving noxious stimulus but no response
      - Amnesia
    - - occasional spontaneous movement
        
        appearance of light anaesthesia
    - - precipitate seizure activity
    - - sympathomimetic
        
        increased sympathetic tone
        
        Increased heart rate and contractility
        
        Increased cardiac output
        
        Increased blood pressure
        
        Increased myocardial oxygen requirement
        
        Due to drug and not increased contractility
        
        :!!: Care with hypertrophic cardiomyopathy
      - Beware in animals with limited sympathetic reserves
      - Only in normal healthy animals
    - - apneustic pattern of breathing
      - bronchodilation
    - - Clinical consequence in large animals
  - - - Less side effects
    - - More effective in chronic than acute pain
    - - High sympathetic tone
        
        Hyperthyroidism
        
        Phaechromocytoma
        
        Adrenal medulla tumour which produces adrenaline/noradrenaline
      - HCM
      - Increased intracranial pressure
      - Glaucoma
      - Epilepsy
- - - - highly lipid soluble
        
        crosses BBB easily
        
        rapid induction
        
        Increased solubility in water via preparations
        
        Act as nutrient medium
        
        Support microbial growth and endotoxin production
      - High PPB
      - Weak organic acid
        
        Almost entirely unionised at pH 7.4
    - - rapid
      - hepatic metabolism
        
        quinol sulphate and glucoronide conjugates
        
        extra-hepatic metabolism sites
        
        kidney, brain, lungs
      - little accumulation of drug
        
        repeated doses possible
        
        :!!:repeated exposure to preservative may result in toxicity
        
        Preservative free formulation available
        
        lack glucoronyl transferase
        
        problems with triglyceride metabolism
        
        difficult to metabolise lipid carrier of propofol
        
        slower recovery
        
        higher risk of accumulation
        
        Oxidative injury to RBC possible
        
        Heinz body formation
        
        Anaemic
        
        Advised not to do continual infusion of propofol in cats
  - - - reduced systemic vascular resistance
        
        hypotension
      - blunts baroreceptor response
        
        no compensatory tachycardia
        
        reduced contractility
      - :red_cross: arrhythmogenic
      - :red_cross: sensitisation to catecholamines
    - - bronchodilation
      - Apnoea
        
        Can be prevented by giving drug slowly
    - - sometimes muscle twitching
        
        Not linked to anaesthetic depth
        
        Palpebral reflex will not be present
      - opistontonus
        
        subcortical excitratory-inhibitory centre imbalance
    - - reduce in intracranial pressure
        
        reducing cerebral blood flow
      - reduces cerebral metabolic rate
    - - must be given i/v to be effective :warning:
- - - - NMDA antagonist
      - sympathomimetic actions
  - - - rapid uptake
        
        rapid induction
  - - - dilute oxygen in alveoli
        
        hypoxia
        
        supplement oxygen after N2O turned off
  - - - gastric dilatation and volvulus
      - closed pneumothorax
      - air emboli
  - - - reduction in vitamin B12
        
        blood dyscrasias
        
        marrow suppresion
        
        neurologic deficits
        
        infertility problems
- - - - one injection site-brain circulation time
        
        Better than ketamine because faster onset
        
        Propofol and alfaxalone diluted for small animals
        
        Not suited for large animals
    - - Effects
        
        CVS depression
        
        hypotension
        
        reduction in contractility
        
        compensatory tachycardia
        
        ventricular arrhythmias
        
        Reduces systemic vascular resistance
        
        dose dependent respiratory depression
        
        no analgesia
        
        poor muscle relaxation
        
        anticonvulsant
        
        decrease intracranial pressure
        
        Irritant on perivascular injection
        
        I/v cannula
      - Intraoperative top ups when inadequate depth of anaesthesia in large animas
        
        Not recommended for maintenance
    - - i/v horses
        
        Irrritant perivascularly
        
        Haemolytic, haemoglobinurai, Heinz body formation, phlebitis
      - central skeletal muscle relaxant
        
        spinal cord and brain stem
        
        Risk of apnoea
      - not anaesthetic and no analgesia
      - no CVS side effects
      - dose dependent respiratory effects
      - Not a NMB
      - Active metabolite
        
        Catechol
        
        Accumulation
        
        Poor quality recovery
      - Bought as infusion fluid bags and mix with other drugs
      - thiopental
  - - - concentrated, non-sterile preparations
  - - - Massively prolong recovery which is poor
      - Higher risk of accumulation if rapid administration
  - - - decreased adrenal gland function
- - - - cessation of clinical effect
  - - - easily excreted
- - - - act within brain
    - - Induction
      - Maintenance
      - Supplementation to inhalational
      - Treatment of status epilepticus
      - Long term sedation in intensive care
    - - TIVA
        
        total i/v anaesthesia
        
        Incremental doses
        
        Continual infusion
      - PIVA
        
        partial i/v anaesthesia
      - Method
        
        i/v boli
        
        i/v infusion
        
        combination of inhalational and injectable agents
        
        Complicated
        
        single i/m injection
    - - Injection>Heart>Brain
    - - Rapid onset and recovery
      - :red_cross: excitation
      - :check: analgesia
      - :red_cross: pain on injection
      - Safe
        
        extravascular
        
        intra-arterial
      - Minimal CVS and respiratory depression
      - :red_cross: histamine release
      - :red_cross: toxic effects or interactions with other agents
      - High lipid solubility
        
        Increase potency and reduced required dose
      - :red_cross: accumulation
      - water soluble
      - Long shelf life
      - Inexpensive
    - - depends on
        
        Species and temperament
        
        Underlying medical conditions
        
        Procedure
        
        Short
        
        Available drugs, equipment and conditions
        
        Personal preference and experience
    - - Minimal equipment required
      - No pollution from gases and inhalation agents
    - - Uptake
        
        Time to reach adequate effect site levels
        
        Problems
        
        Valve incomepetence
        
        Low circulatory volume
      - Distribution
        
        Depends on Qt and distribution of blood flow
        
        Link between distribution and metabolism
        
        Redistribution to other tissues away from the effect site causes cessation of clinical effect
        
        Equilibration
      - Metabolism
        
        Depends on drug and species
        
        Hepatic metabolism
        
        Extra-hepatic sites may be involved
        
        Lack of liver does not mean no metabolism
      - Elimination
  - - - Volatile liquids
        
        Isoflurane
        
        Sevoflurane
        
        Desflurane
        
        Halothane
      - Compressed gases
        
        Xenon
        
        Nitrous Oxide
    - - Increased fraction of oxygen
      - Airway protection by endotracheal tube
      - Rapid induction, recovery and change in anaesthetic depth
    - - Require additional equipment
      - Require control of waste gases
        
        prevent personnel exposure
      - Toxic compounds may be produced
        
        contact with soda lime or by liver metabolism
    - - Easily vapourised
      - Non-inflammable, non-explosive
      - Inert
        
        Stable on storage
      - Non-irritant
      - Minimally meatbolised/ produce non-toxic metabolites
        
        no nephro-/hepato- toxicity
      - smooth induction and recovery, rapid change of anaesthetic depth
      - some analgesia and muscle relaxant
      - few CVS and respiratory side effects
      - cheap
      - does not cause environmental damage
    - - Lipid soluble
        
        may slow recovery
      - rate of induction and recovery
        
        rate of change of anaesthetic agent concentration in the prain
        
        brain concentration ~ alveolar concentration
      - Anaesthetic Uptake
        
        In Blood
        
        Blood solubility
        
        blood gas partition coefficient
        
        high solubility
        
        slow induction and recovery
        
        pulmonary blood flow
        
        cardiac output
        
        concentration gradient
        
        In Tissues
        
        tissue solubility
        
        tissue blood partition coefficient
        
        tissue perfusion
        
        concentration gradient
        
        inspired agent concentration
        
        votality and temperature
        
        vaporiser efficiency
        
        absorption by soda lime
        
        alveolar ventilation
        
        breathing rate
        
        tidal volume
      - Metabolism
        
        Halothane
        
        Sevoflurane
        
        Isoflurane
        
        Desflurane
      - Elimination
        
        lungs
        
        similar factors to uptake
        
        extent of metabolism
        
        duration of anaesthesia
        
        lipid soluble
      - Minimum Alveolar Concentration
        
        depends on
        
        species
        
        age
        
        Temperature extremes
        
        high circulating catecholamines
        
        pregnancy
        
        Hypotension
        
        hyperthyroidism
        
        CNS stimulants or depression
        
        sedatives and analgesia
        
        extremes of O2 and CO2 concentration
        
        do not depend on
        
        sex
        
        duration of anaesthesia
        
        blood pH
        
        normal O2 and CO2 concentration
        
        moderate anaemia
        
        High mean arterial pressure
    - - :red_cross: analgesia
      - dose dependent CVS and respiratory depression
        
        negative inotropy
        
        halothane>> Isoflurane, sevoflurane
        
        peripheral vasodilation
        
        isoflurane, sevoflurane >> halothane
        
        hypotension
        
        reduced cardiac output and blood pressure
        
        dampen chemoreceptor sensitivity
        
        dampen hypoxic pulmonary vasocontriction response
        
        decrease in tidal volume and minute ventilation