Download 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
 Long-acting
 Phenobarbital – used as a sedative &
anticonvulsant
Action of Barbiturates
 Mimics the inhibitory neurotransmitter GABA
 Depresses nerve impulses to cerebral cortex resulting in
CNS depression and loss of consciousness
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
 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
 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 lipid 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
 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
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 in 20 min in dogs, 30 min 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*
 Now there is propofol-28
 Lasts up to 28 days
Etomidate
 Noncontrolled, ultra short acting nonbarbiturate, sedative-hypnotic
 Minimal effects on the cardiovascular and respiratory systems
 Expensive
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
 Triple drip: GG, ketamine, xylazine
 Used in horses
 Not a sedative or analgesic
 Must pre-medicate
 Alpha-2’s or acepromazine
 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
 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
 Increased dose prolongs duration but doesn’t
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
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 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