Ch. 3

1
Injectable Anesthetics

• Ch. 3

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Injectable anesthetics

• Can produce unconsciousness when given alone
• In general, dont provide analgesia or muscle
  relaxation
• Administered IV, titration method
• Classes include
• Barbiturates
• Non-barbiturates
• Dissociatives

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Injectable anesthetics

• Barbiturates
• Ultra-short acting
• Short-acting
• Intermediate acting
• Long-acting
• Non-barbiturates/Hypnotics
• Propofol
• Etomidate
• Dissociatives
• Ketamine
• Tiletamine

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BARBITURATES

• ULTRA-SHORT ACTING
• SHORT ACTING
• INTERMEDIATE ACTING
• LONG ACTING

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Barbiturates

• Derivatives of barbituric acid
• Controlled
• No analgesia
• No reversal agent

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Classes of Barbiturates

• Based on duration of action
• Ultrashort
• Thiopental sodium, methohexital, and thiamylal
• Used in dogs, cats, horses
• Short
• Pentobarbital
• Used in laboratory animals
• May be used to treat status epilepticus and for
  euthanasia

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Classes of Barbiturates

• Most intermediate and long acting barbiturates
  are no longer used as anesthetics
• Long-acting
• Phenobarbital used as a sedative
  anticonvulsant

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Action of Barbiturates

• Mimics the inhibitory neurotransmitter GABA
• Depresses nerve impulses to cerebral cortex
  resulting in CNS depression and loss of
  consciousness

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Pharmacodynamics of Barbiturates

• Factors that affect potency, onset, and duration
  of action
• Ionization
• Non-polar (non-ionized) forms pass through the
  cell membranes
• Acidosis (blood pH lt7.4)
• Increases non-ionized form of the drug
• Increased drug amounts to brain
• Exaggerated patient response
• Lower doses should be used to anesthetize an
  acidotic animal

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Pharmacodynamics of Barbiturates

• Protein binding
• Travels in blood bound to proteins
• Free (unbound) drug enters the brain
• So
• Hypoproteinemia results in more free drug
• More drug goes to the brain
• Normal drug dose may actually produce prolonged
  unconsciousness or death

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Pharmacodynamics of Barbiturates

• Lipid solubility (partition coefficient)
• Is the tendency of the drug to dissolve in fats,
  oils, and lipids
• Affects the ability to penetrate the cell
  membrane fatty layer

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Pharmacodynamics of Barbiturates

• High lipid solubility results in
  ultrashort-acting drug
• Passes into the brain cells more quicklyfaster
  onset of action
• High solubility results in rapid tissue
  redistribution
• Moderate solubility results in short-acting drug
• metabolized by the liver takes longer than
  redistribution
• Low lipid solubility results in long acting drug
• excreted primarily through the kidneys longest
  process

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Redistribution How it works

• Ultrashort acting Thiopental sodium is given IV.
  It then travels to the brain (vessel rich). It is
  highly lipid soluble and crosses into brain cells
  quickly.
• Patient is now unconscious 30 seconds
• Once the levels in the brain are higher than in
  the blood, the molecules will move back down the
  concentration gradient
• Drug re-enters circulation
• Redistributes to muscle, fat and other body
  tissues
• Patient begins to recover in 10-15 minutes
• Over the next couple of hours thiopental is
  released from muscle and fat and eliminated from
  the body by liver metabolism and excretion of
  metabolites in the urine

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Barbiturate Redistribution

• Thiopentalultrashort-acting
• Released from muscle and fat and metabolized by
  liver, excreted by kidneys
• Continuous or repeated dosing may lead to full
  muscle and fat and increased brain levels
  prolonged recovery and possible death
• Methohexitalultrashort-acting
• Released from muscle and fat but metabolized
  faster
• Muscle and fat dont get full so there is no
  prolonged recovery with continuous or repeated
  doses

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Barbiturates
EFFECTS
ADVERSE EFFECTS
EFFECTS
ADVERSE EFFECTS
EFFECTS
ADVERSE EFFECTS
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Barbiturates

• Effects on sighthounds
• Effect on critically ill animals
• Effect on tissues

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Barbiturates

• Effects during induction/recovery
• Interaction with other drugs

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Thiopental

• Ultrashort-acting
• Small animals and horses
• duration of action10-15minutes
• Reconstitute with sterile water, normal saline,
  or 5 dextrose in water
• Shelf life 1 week refrigerated or 3 days at room
  temperature
• Dont use if a precipitate is present
• Sighthounds avoid use

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Methohexital

• Ultrashort-acting
• Can be useful on an unfasted animal
• Rapid induction and intubation
• Decreased risk of vomitus aspiration
• A powder that must be reconstituted (sterile
  water)
• Shelf life6 weeks without refrigeration
• More expensive than thiopental
• Can be used in sighthounds
• Excitement and seizures during induction and/or
  recovery
• Premedicate with tranquilizer
• Control postoperative seizures with diazepam IV
• Dont use in animals with epilepsy

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Pentobarbital

• Short acting
• Largely replaced by propofol
• Administered IP to rodents for general anesthesia
• Status epilepticus- treatment, persistent seizure
• Administer IV to stop seizure and produce heavy
  sedation
• Narrow margin of safety
• Euthanasia

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NON-BARBITURATES

• PROPOFOL
• ETOMIDATE

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Propofol

• Ultrashort-acting, non-barbiturate anesthetic
• Most commonly used injectable anesthetic
• Give IV for anesthetic induction and short-term
  maintenance
• affects GABA receptors similar to barbiturates
• Other use
• IV bolus and CRI to treat status epilepticus in
  dogs and cats

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Propofol

• Available in an egg lecithin/glycerin/soybean oil
  aqueous solution
• Milky white appearance
• Highly lipid soluble rapid onset, re-disribution,
  and rapidly metabolized
• Onset of action30-60 seconds
• Duration of action5-10 minutes
• Complete recovery in 20 min in dogs, 30 min in
  cats

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Effects of Propofol
EFFECTS
ADVERSE EFFECTS
EFFECTS
ADVERSE EFFECTS
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Effects of Propofol
EFFECTS
ADVERSE EFFECTS
EFFECTS
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Other Effects of Propofol

• Some dogs may exhibit muscle twitching during
  induction
• Safe in animals with liver or kidney disease
  because of its rapid metabolism

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Use of Propofol

• IV slowly, give ¼ dose every 30 seconds, but
  dont give too slowly because it might cause
  excitement
• IM administration produces mild sedation and
  ataxia only
• Highly protein bound
• Dont use in hypoproteinemic animals

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Propofol Handling and Storage

• Poor storage characteristics
• Egg lecithin, glycerol, and soybean oil support
  bacterial growth
• Use aseptic technique- always write time and date
  on bottle
• Discard unused drug within 6 hours of opening
• May keep in refrigerator up to 24 hours
• Now there is propofol-28
• Lasts up to 28 days

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Etomidate

• Noncontrolled, ultra short acting nonbarbiturate,
  sedative-hypnotic
• Minimal effects on the cardiovascular and
  respiratory systems
• Expensive

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Etomidate Mode of Action

• Similar to barbiturates and propofol
• Increased GABA inhibitory action- hypnosis with a
  little analgesia
• Wide margin of safety

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Effects of Etomidate
EFFECTS
ADVERSE EFFECTS
EFFECTS
ADVERSE EFFECTS
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Effects of Etomidate
EFFECTS
ADVERSE EFFECTS
EFFECTS
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Adverse Effects of Etomidate

• Painful IV injection
• Perivascular sterile abscesses
• Hemolysis with rapid administration (cats)
• Nausea, vomiting, involuntary excitement during
  induction and recovery

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Guaifenesin (GG)

• Noncontrolled muscle relaxant
• Common use in large animals
• Muscle relaxation
• Facilitate intubation
• Ease induction and recovery
• Not an anesthetic or an analgesic
• Mode of action is not understood- blocks nerve
  impulses to the CNS

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Effects of Guaifenesin
EFFECTS
EFFECTS
EFFECTS
EFFECTS
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Adverse Effects of Guaifenesin

• Few adverse effects at therapeutic doses
• Overdose
• Muscle rigidity
• Apneustic respiration
• Perivascular tissue irritation

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Use of Guaifenesin

• Triple drip GG, ketamine, xylazine
• Used in horses
• Not a sedative or analgesic
• Must pre-medicate
• Alpha-2s or acepromazine
• May cause excitement if not
• Increased risk of side effects if not

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DISSOCIATIVES

• KETAMINE
• TILETAMINE

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Mode of action

• Disrupts nerve transmission in some brain
  sections and has selective stimulation in other
  parts of the brain
• Decreases windup through NMDA inhibition
  (N-methyl-D-aspartate)
• Windup is exaggerated response to low-intensity
  pain stimuli that results in worsening of post op
  pain

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Dissociative Anesthetics

• Ketamine hydrochloride
• Derivative of Phencyclidine PCP
• Mostly used to compliment other drugs such as
  Tranquilizers and opioids to induce general
  anesthesia
• Subanesthetic dose can be used as CRI for
  analgesia

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Dissociative Anesthetics

• Tiletamine hydrochloride
• Combined with benzodiazepine zolazepam (Telazol
  )
• Tiletamine is a controlled substance
• No reversal for Telazol
• Provides limited somatic analgesia

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Dissociative Effects
EFFECTS
ADVERSE EFFECTS
EFFECTS
ADVERSE EFFECTS
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Dissociative Effects
EFFECTS
ADVERSE EFFECTS
EFFECTS
ADVERSE EFFECTS
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Dissociative Anesthetic Trancelike State
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Other Adverse Effects of Dissociatives

• Pain after IM injection due to tissue irritation
• Increased intracranial and intraocular pressure

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Ketamine

• Increased dose prolongs duration but doesnt
  increase anesthetic effect
• Duration of effect 20-30 minutes
• All dissociatives are either metabolized in the
  liver or excreted unchanged in the urine
• Avoid use in animals with liver or kidney disease

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Ketamine

• Approved for use in cats and subhuman primates
• Also used in dogs, birds, horses, and exotic
  species
• Administer IV or IM or orally (cats)
• Elimination
• Hepatic metabolismdogs
• Renal metabolismcats

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Ketamine and Diazepam Combination

• IV induction in dogs and cats
• Equal volumes of diazepam and ketamine
• Can be mixed in one syringe
• Watch for possible precipitate
• Alternative combination for IM injection
  midazolam and ketamine
• Minimal cardiac depression
• Superior recovery and some analgesia

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Tiletamine

• Similar to ketamine
• Sold only in combination with zolazepam
  (Telazol)
• Telazolsold as a powder to reconstitute
• Stable for 4 days at room temperature, or 14 days
  if refrigerated
• A class III drug
• Possible long and difficult recoveries
• Tachycardia, and cardiac arrhythmias
• Increased salivation
• Avoid in patients with ASA P3 rating

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Advantages of Telazol (as compared to Ketamine)

• Decreased apneustic respiratory response
• Can be administered SC, IM, or IV