Transcript Injectable Anesthetics - Dr. Roberta Dev Anand

Injectable Anesthetics
Ch. 3
Injectable anesthetics
 Can produce unconsciousness when given alone
 In general, don’t provide analgesia or muscle relaxation
 Administered IV, titration method
 Classes include:
 Barbiturates
 Non-barbiturates
 Dissociatives
Injectable anesthetics
 Barbiturates
 Ultra-short acting
 Short-acting
 Intermediate acting
 Long-acting
 Non-barbiturates/Hypnotics
 Propofol
 Etomidate
 Dissociatives
 Ketamine
 Tiletamine
BARBITURATES
ULTRA-SHORT ACTING
SHORT ACTING
INTERMEDIATE ACTING
LONG ACTING
Barbiturates
 Derivatives of barbituric acid
 Controlled
 No analgesia
 No reversal agent
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
Classes of Barbiturates
 Most intermediate and long acting barbiturates
are no longer used as anesthetics
 Intermediate
 Long-acting
 Phenobarbital – used as a sedative &
anticonvulsant
Barbiturates
 Subclasses based on chemical structure
 Oxybarbiturates
 Phenobarbital, pentobarbital, and methohexital
 Thiobarbiturates
 Thiopental and thiamylal
Action of Barbiturates
 Mimics the inhibitory neurotransmitter GABA
 Depresses nerve impulses to cerebral cortex resulting in
CNS depression and loss of consciousness
 Termination of action
 After agent leaves brain:
 Is metabolized, excreted, or redistributed
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 <7.4)
 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
Pharmacodynamics of Barbiturates
 Factors that affect potency, onset, and duration of action
 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
Pharmacodynamics of Barbiturates
 Factors that affect potency, onset, and duration of
action
 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
Pharmacodynamics of Barbiturates
 High solubility results in ultra–short-acting drug

Passes into the brain cells more quickly=faster 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
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
Barbiturate Redistribution
Variations of
Barbiturate Redistribution
 Thiopental—ultra–short-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
 Methohexital—ultra–short-acting
 Released from muscle and fat but metabolized faster
 Muscle and fat don’t get “full” so there is no prolonged recovery with
continuous or repeated doses
Variations of
Barbiturate Redistribution (Cont’d)
 Phenobarbital—long acting- low lipid solubility
 Sustained effect caused by slow uptake and release from the brain
 Release is dependent on kidney excretion, which is slowest
 Pentobarbital—short acting- intermediate solubility
 Brain levels decrease based on liver metabolism
 Faster than kidney excretion
Barbiturates
EFFECTS:
ADVERSE EFFECTS:
EFFECTS:
ADVERSE EFFECTS:
EFFECTS:
ADVERSE EFFECTS:
Barbiturates
 Effects on sighthounds:
 Effect on critically ill animals:
 Effect on tissues:
Barbiturates
 Effects during induction/recovery:
 Interaction with other drugs:
Thiopental
 Ultra–short-acting
 Small animals and horses
 duration of action:10-15minutes
 Reconstitute with sterile water, normal saline, or 5%
dextrose in water
 Shelf life: 1 week refrigerated or 3 days at room temperature
 Don’t use if a precipitate is present
 Sighthounds – avoid use
Methohexital
Ultra–short-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 life—6 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
 Don’t use in animals with epilepsy

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
NON-BARBITURATES
PROPOFOL
ETOMIDATE
Propofol
 Ultra–short-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
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 action:30-60 seconds
 Duration of action:5-10 minutes
 Complete recovery
 20 minutes in dogs
 30 minutes in cats
Effects of Propofol
EFFECTS:
ADVERSE EFFECTS:
EFFECTS:
ADVERSE EFFECTS:
Effects of Propofol
EFFECTS:
ADVERSE EFFECTS
EFFECTS:
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
Use of Propofol
 IV slowly, give ¼ dose every 30 seconds, but don’t give
too slowly because it might cause excitement
 IM administration produces mild sedation and ataxia
only
 Highly protein bound
 Don’t use in hypoproteinemic animals
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*
 more expensive than ketamine-diazepam or thiopental
 Now there is propofol-28
 Lasts up to 28 days
Etomidate
 Noncontrolled, ultra short acting nonbarbiturate, sedative-hypnotic
 Used for induction—dogs, cats, exotics
 Minimal effects on the cardiovascular and respiratory systems
 Expensive
 Pain with IV injection
Etomidate Mode of Action
 Similar to barbiturates and propofol
 Increased GABA inhibitory action- hypnosis with a
little analgesia
 Wide margin of safety
Effects of Etomidate
EFFECTS:
ADVERSE EFFECTS
EFFECTS:
ADVERSE EFFECTS
Effects of Etomidate
EFFECTS:
ADVERSE EFFECTS
EFFECTS:
Adverse Effects of Etomidate
 Painful IV injection
 Perivascular sterile abscesses
 Hemolysis with rapid administration (cats)
 Nausea, vomiting, involuntary excitement during
induction and recovery
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
Effects of Guaifenesin
EFFECTS:
EFFECTS:
EFFECTS:
EFFECTS:
Adverse Effects of Guaifenesin
 Few adverse effects at therapeutic doses
 Overdose
 Muscle rigidity
 Apneustic respiration
 Perivascular tissue irritation
Use of Guaifenesin
 Used with ketamine in anesthetic induction protocol
 Premedicate with alpha2-agonist or acepromazine
 Triple drip: GG, ketamine, xylazine
 Used in horses
 Maintain anesthesia for less than an hour
 Not a sedative or analgesic
 Must premedicate
 May cause excitement if not
 Increased risk of side effects if not
DISSOCIATIVES
KETAMINE
TILETAMINE
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
Dissociative Anesthetics
 Ketamine hydrochloride
 Derivative of Phencyclidine PCP
 Can be used alone in cats for minor procedures or to facilitate
restraint
 Mostly used to compliment other drugs such as Tranquilizers and
opioids to induce general anesthesia
 Subanesthetic dose can be used as CRI for analgesia
Dissociative Anesthetics
 Tiletamine hydrochloride
 Combined with benzodiazepine zolazepam (Telazol® )
 Tiletamine is a controlled substance
 No reversal for Telazol
 Provides limited somatic analgesia
Dissociative Effects
EFFECTS:
ADVERSE EFFECTS
EFFECTS:
ADVERSE EFFECTS
Dissociative Anesthetic Trancelike
State
Other Adverse Effects of Dissociatives
 Pain after IM injection due to tissue irritation
 Increased intracranial and intraocular pressure
Ketamine
 Duration of effect: 20-30 minutes
 Increased dose prolongs duration but doesn’t increase
anesthetic effect
 All dissociatives are either metabolized in the liver or
excreted unchanged in the urine
 Avoid use in animals with liver or kidney disease
Ketamine
 Approved for use in cats and subhuman primates
 Also used in dogs, birds, horses, and exotic species
 Schedule III drug (United States) prescription drug (Canada)
 Administer IV or IM or orally (cats)
 Elimination
 Hepatic metabolism—dogs
 Renal metabolism—cats
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
Tiletamine
 Similar to ketamine
 Sold only in combination with zolazepam (Telazol®)
 Telazol®—sold 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
Advantages of Telazol®
(as compared to Ketamine)
 Decreased apneustic respiratory response
 Can be administered SC, IM, or IV
 Used effectively in some wildlife