Anesthetic agents and adjuncts

1Copyright © 2011, 2003, 2000, 1994 by Mosby, Inc., an affiliate of Elsevier Inc.
Anesthetic Agents and Adjuncts
Anesthetic agent: any drug used to induce a loss of
sensation with or without unconsciousness
Adjunct: a drug that is not a true anesthetic, but that is
used during anesthesia to produce other desired effects
such as sedation, muscle relaxation, analgesia,
reversal, neuromuscular blockade, or parasympathetic
blockade
Chapter 3

Classification of Anesthetic Agents
and Adjuncts
 Route of administration
 Inhalant
 Injectable
 Oral
 Topical
 Time of administration
 Preanesthetic
 Induction
 Maintenance

Classification of Anesthetic Agents
and Adjuncts (Cont’d)
 Principal effect
 Local vs. general
 Sedatives and tranquilizers vs. analgesics
 Neuromuscular blockers
 Anticholinergic agents
 Reversal agents
 Chemistry

Anesthetic Agent and Adjunct Actions
 Pharmacokinetics
 Pharmacodynamics
 Drug distribution
 Target tissues and stimulation
 CNS—depression or stimulation

Agonists
 Bind to and stimulate target tissue
 Most anesthetic agents and adjuncts

Antagonists
 Bind to target tissue but don’t stimulate
 Reversal agents

Partial Agonists and Agonist-
Antagonists
 Opioids
 Partial agonists
 Agonist-antagonists
 Used to block pure agonists

Analgesia
 Most general anesthetics are not analgesics
 Must provide analgesic pre- and
postoperatively
 No pain perception while anesthetized
 True analgesics don’t provide general
anesthesia

Drug Combinations
 Don’t mix drugs in a single syringe unless
they are compatible
 Don’t administer a drug combination if a
precipitate develops when the drugs are
mixed
 Most anesthetic agents and adjuncts are
water soluble
 Diazepam is not water soluble

Preanesthetic Medications
 Calm or sedate excited animal
 Minimize adverse drug effects
 Reduce dose of concurrent drugs
 Smoother anesthetic induction and recovery
 Analgesia
 Muscle relaxation

Preanesthetic Medications (Cont’d)
 Route of administration affects onset of action
and duration of effects
 SC—slowest onset, longest duration
 IM—faster onset, shorter duration
 IV—fastest onset, shortest duration

Preanesthetic Anticholinergics
 Parasympatholytic drugs—block acetylcholine
 Prevent and treat bradycardia
 Decrease salivary secretions
 Atropine and glycopyrrolate (dogs and cats)
 IV, IM, SC, or IT
 Atropine—faster onset, shorter peak, shorter
duration
 Glycopyrrolate—slower onset, longer peak, longer
duration

Anticholinergic Effects
 CNS—limited effect
 Cardiovascular—prevent bradycardia
 Secretions—decrease
 Eye—mydriasis and corneal drying
 Bronchodilation

Anticholinergic Adverse Effects
 Cardiac arrhythmia
 Contraindicated in animals with elevated heart
rates or cardiac diseases
 Temporary bradycardia—atropine
 Thickened respiratory and salivary secretions
 May lead to airway blockage—cats and ruminants
 Intestinal peristalsis inhibition
 May lead to colic (horses) or bloat (ruminants)

Tranquilizers and Sedatives
 Phenothiazines
 Benzodiazepines
 Alpha2-adrenoceptor agonists
 Alpha2-antagonists

Phenothiazines—Acepromazine
Maleate
 Also known as acepromazine or “ace”
 Preanesthetic sedation
 Decrease dose of general anesthetic
 Ease induction and recovery
 May be used with opioids for minor procedures
 Approved for horses, dogs, and cats
 Administered IV or IM
 No reversal agent
 Metabolized by liver
 Will slowly cross the placenta

Effects of Acepromazine
 CNS
 Calming, reluctance to move, decreased interest
in surroundings
 Sedation less pronounced in cats
 Not an analgesic
 Cardiovascular System
 Peripheral vasodilation that leads to hypotension,
increased heart rate, and hypothermia
 Protects against arrhythmias and decreases
cardiac output

Effects of Acepromazine (Cont’d)
 Respiratory system
 Worsens depressive effect of other drugs
 Gastrointestinal system
 Antiemetic
 Prevents histamine release and decreases
allergic response

Adverse Effects of Acepromazine
 CNS
 Reduced seizure threshold
 May produce aggression or excitement
 Cardiovascular system
 Hypotension—dose dependent
 Penile prolapse
 Seen in horses and other large animals
 May lead to permanent injury
 Decreased PCV
 Possibly due to splenic engorgement

Use of Acepromazine
 Dose and needle placement
 Increased potency and duration
 Geriatrics, neonates, debilitated animals
 Breed considerations
 Australian shepherds
 Giant breeds, Boxers, Greyhounds
 Terriers and cats
 Overdose treatment

Benzodiazepines
 Tranquilizers—controlled substances
 Diazepam
 Zolazepam
 Midazolam
 Rapid onset of action
 Short duration of action

Effects of Benzodiazepines
 CNS
 Calming and antianxiety only in old or ill patients
 Not an effective sedative or analgesic
 Anticonvulsant—use with animals having seizures
 Cardiovascular and respiratory systems
 Minimal effect with a high margin of safety
 Skeletal muscle relaxation
 Potentiate general anesthetics
 Appetite stimulation (cats and ruminants)

Adverse Effects of Benzodiazepines
 CNS
 Disorientation and excitement—young, healthy
dogs
 Dysphoria and aggression—cats
 Muscle fasciculations—horses
 Ataxia and recumbency—any large animal
 Diazepam must be given by IV slowly
 Oral diazepam in cats can cause liver failure

Use of Benzodiazepines
 Diazepam
 Not water soluble
 Don’t mix with water-soluble drugs
 Don’t store in plastic
 Commonly used with ketamine to induce
anesthesia in small animals and horses
 Administer IV slowly

Use of Benzodiazepines (Cont’d)
 Midazolam
 Water soluble
 Can be administered IM or SC
 Excellent sedative for swine, ferrets, rabbits, and
birds
 Used in combination with ketamine to induce
anesthesia in dogs, small mammals, and birds

Use of Benzodiazepines (Cont’d)
 Zolazepam
 Available only as a component of Telazol®
 A powdered product
 Reconstituted with sterile water

Alpha2-Adrenoceptor Agonists
 Also written alpha2-agonists or α2-agonists
 Noncontrolled agents
 Sedation, analgesia, and muscle relaxation
 Large and small animals—IM or IV
 Administered prior to minor procedures
 Readily reversed with alpha2-antagonist

Alpha2-Agonists
 Xylazine (Rompun, Anased)
 Detomidine (Dormosedan)
 Romifidine (Sedivet)
 Dexmedetomidine (Dexdomitor)

Alpha2-Agonists (Cont’d)
 Stimulates alpha2 receptors of the sympathetic
nervous system (SNS)
 Decrease release of norepinephrine
 No “fight-or-flight” response
 Sedation, analgesia, bradycardia,
hypotension, and hypothermia
 Metabolized in liver; excreted in urine
 Rapid sedation; 1-2 hour duration

Effects of Alpha2-Agonists
 CNS
 Dose-dependent sedation
 Analgesia—short-acting
 Cardiovascular system—early phase
 Dose-dependent vasoconstriction and
hypertension
 Bradycardia
 Cardiac arrhythmias
 Cardiovascular system—late phase
 Decreased cardiac output
 Hypotension and further bradycardia

Effects of Alpha2-Agonists (Cont’d)
 Dose-dependent depression
 Other effects
 Muscle relaxation
 Increased effect of other anesthetic agents
 Vomiting—immediate response (dogs and cats)
 Hyperglycemia—transient
 Hypothermia

Adverse Effects of Alpha2-Agonists
 CNS
 Change in behavior—varies with species
 Bradycardia, hypotension, decreased output
 Depression—varies from animal to animal
 More severe if given with other drugs

Adverse Effects of Alpha2-Agonists
(Cont’d)
 Increased urination
 Gastrointestinal effects
 Bloat—dogs, cattle, and horses
 Salivation and regurgitation—cattle
 Premature parturition—cattle (last trimester)
 Sweating—horses
 Absorbed through skin abrasions and
mucous membranes
 Wash off immediately

Use of Alpha2-Agonists
 Use with caution; monitor patients closely
 Avoid use in geriatric, diabetic, pregnant,
pediatric, or ill patients
 Administer anticholinergics 10-20 minutes
prior

Alpha2-Agonist—Xylazine
 2% solution (small animals)
 10% solution (horses)
 Use 1/10 horse dose in cattle
 Used mostly in large animals

Alpha2-Agonist—Dexmedetomidine
 Dexdomitor®
 Most commonly used in dogs and cats
 Produces sedation and analgesia
 More potent and safer than xylazine
 Antagonist—atipamazole (Antisedan®
)
 Preanesthetic in low doses
 Can be mixed with other drugs

Alpha2-Agonists—Detomidine and
Romifidine
 Detomidine
 Used in horses
 Sedation, analgesia, muscle relaxation
 Two times the duration of xylazine
 Standing sedation with butorphanol
 Romifidine
 Produces less ataxia

Alpha2-Antagonists
 Reverse all effects of alpha2-agonists
 Beneficial effects—for example, analgesia and
sedation
 Detrimental effects—for example, bradycardia
 Wide margin of safety
 Effects of overdose
 Neurological—excitement and muscle tremors
 Cardiovascular—hypotension and tachycardia
 Gastrointestinal—salivation and diarrhea

Use of Alpha2-Antagonists
 Dose is expressed as a ratio
 Agonist to antagonist
 10:1 means the dose of the antagonist is 1/10 of
the dose of the agonist
 Administer slowly by IV
 Reduce dose if more than 30 minutes has
elapsed since the agonist was administered

Alpha2-Antagonist—Tolazoline
 Nonspecific alpha2-antagonist
 Used in ruminants at a 1:10 dose ratio with
xylazine
 Reverses cardiovascular and sedative effects

Alpha2-Antagonist—Yohimbine
 Used in dogs, cats, horses, and exotic
species
 Reverses cardiovascular and sedative effects
of xylazine
 Dose ratio is species dependent
 Dogs and horses—10:1
 Cats—2:1

Alpha2-Antagonist—Atipamezole
 Antisedan®
 Specific antagonist for dexmedetomidine
 IM injection (IV in emergencies)
 Use ½ the dose in cats compared to dogs
 Reversal—5-10 minutes after IM injection

Opioids
 Derivatives of opium
 Opiates—naturally derived compounds
 Produce analgesia and sedation
 Anesthetic induction when combined with
other drugs
 Classified as agonists, partial agonists,
agonist-antagonists, or antagonists

Commonly Used Opioids
 Agonists
 Morphine, hydromorphone, oxymorphone,
fentanyl, and meperidine
 Partial agonist
 Buprenorphine
 Butorphanol and nalbuphine
 Antagonists
 Naloxone, etorphine, and carfentenil

Opioids
 Controlled substances
 Except for antagonists and nalbuphine
 Administered IV, IM, SC, oral, rectal,
transdermal, subarachnoid, and epidural

Opioids—Pharmacodynamics
 Mimic endogenous opioid peptides
 β-Endorphins, dynorphins, enkephalins
 Analgesia and sedative effects
 Result of action on the receptors in the brain and
spinal cord
 Types of receptors
• Mu (μ), kappa (κ), and delta (δ), plus many subtypes
• Each opioid has a different action at each receptor

Opioids—Pharmacodynamics
(Cont’d)
 Agonists
 Bind to and stimulate mu and kappa receptors
 Best for moderate to severe pain
 Partial agonists
 Bind to and partially stimulate receptors
 Bind to mu and kappa receptors, but stimulate
only kappa receptors
 Antagonists
 Bind to but don’t stimulate mu and kappa
receptors

Effects of Opioids
 CNS
 Effect depends on many factors
 Dogs
• Causes sedation
• Narcosis
 Cats, horses, and ruminants
• Causes CNS stimulation
• Bizarre behavior patterns or dysphoria
• Use lower dose
 Analgesia
• Pure agonists are most effective against severe pain
• Used as a premedication for painful surgery

Effects of Opioids (Cont’d)
 Bradycardia
 Minimal decreased rate and tidal volume

Other Effects of Opioids
 Miosis in dogs
 Mydriasis in cats, horses, and ruminants
 Hypothermia in dogs
 Hyperthermia in cats
 Increased responsiveness to noise
 Sweating in horses
 Decreased urine production with urine
retention

Adverse Effects of Opioids
 CNS
 Anxiety, disorientation, excitement, dysphoria
 Pronounced bradycardia
 Decreased respiration and tidal volume
 Decreased PaO2 and PaCO2
 Dose dependent with some agents
 Ceiling effect with some agents

Adverse Effects of Opioids (Cont’d)
 Gastrointestinal system
 Salivation and vomiting—small animals
 Initial diarrhea, vomiting, and flatulence
 Pretreat with atropine or acepromazine
 GI stasis follows initial GI stimulation
• May predispose to colic in horses
• Avoid administration to any animal with a GI obstruction

Other Adverse Effects of Opioids
 Addiction (physical dependence)
 Facial swelling and hypotension
 Increased intraocular and intracranial
pressure
 Drug interactions
 Meperidine and MOA inhibitors or tricyclic
antidepressants (human)

Use of Opioids
 Preanesthetic
 Agonists, partial agonists, or agonist-antagonist
 May be used alone or in combination with
• Tranquilizers
• Anticholinergics
 Analgesia
 Prevent and treat postoperative pain
 Used with tranquilizer to produce
neuroleptanalgesia

Neuroleptanalgesia
A profound state of sedation and analgesia
induced by simultaneous administration of an
opioid and a tranquilizer

Neuroleptanalgesia (Cont’d)
 Opioids
 Morphine
 Buprenorphine
 Butorphanol
 Hydromorphone
 Tranquilizers
 Acepromazine
 Diazepam
 Midazolam
 Xylazine
 Dexmedetomidine

Use of Neuroleptanalgesics
 Sedation for minor procedures
 Induction of general anesthesia—dogs
 Not in young, healthy dogs
 Not in cats

Opioid Antagonists
 Reverse undesirable effects
 CNS and respiratory depression
 Wake up patient following sedation
 Naloxone hydrochloride
 IM or slow IV administration
 Dogs, horses, cats, exotic mammals
 Naltrexone
 Used in wild animals
 Longer lasting

Naloxone Hydrochloride
 Mechanism of action is unknown
 IM—5 minutes to reversal
 IV (slowly)—2 minutes to reversal
 Duration of action 30-60 minutes

Effects of Opioid Antagonists
 Reversal of effects of opioid agonists, partial
agonists, and agonists-antagonists
 Reversal can be complete in a few minutes
 Adverse effects are rare
 Sudden analgesia loss can cause excitement,
anxiety, and sympathetic nervous system
stimulation
 Prevent by using an agonist-antagonist

Use of Opioid Antagonists
 Emergencies
 Overdose
 Reverse neuroleptanalgesia
 Reviving neonates delivered by C-section
 If dam received opioids
 One drop placed under the tongue

Injectable Anesthetics
 Can produce unconsciousness
 Don’t provide analgesia or muscle relaxation
 Used with other agents
 Administered “to effect” IV
 Barbiturates, propofol, and etomidate

Barbiturates
 Subclasses based on duration of action
 Ultrashort
• Thiopental sodium, methohexital, and thiamylal
• Dogs, cats, and horses
• Induce general anesthesia
 Short
• Pentobarbital
• Laboratory animals
• Induce general anesthesia
• Treat epilepsy in small animals
 Intermediate
 Long-acting

Barbiturates (Cont’d)
 Subclasses based on chemical structure
 Oxybarbiturates
• Phenobarbital, pentobarbital, and methohexital
 Thiobarbiturates
• Thiopental and thiamylal

Action of Barbiturates
 Not fully understood
 Mimics the inhibitory neurotransmitter GABA
 Causes CNS depression and loss of
consciousness
 Termination of effect
 Agent leaves brain
 Is metabolized, excreted, or redistributed

Pharmacodynamics of Barbiturates
 Affect potency, onset, and duration of action
 Ionization
 Polar (ionized) and nonpolar (nonionized) forms
 Nonpolar forms pass through the cell membranes
 Acidosis (blood pH <7.4)
• Increased nonpolarization
• Increased drug amounts to brain
• Exaggerated patient response
• Lower dose to anesthetize an acidotic animal

(Cont’d)
 Protein binding (plasma proteins)
 Free (unbound) drug enters the brain
 Hypoproteinemia results in more free drug
 Increased drug amounts to brain
 Normal drug dose may produce prolonged
unconsciousness or death

(Cont’d)
 Lipid solubility (partition coefficient)
 Tendency of the drug to dissolve in fats, oils, and
lipids
 Affects the ability to penetrate the cell membrane
fatty layer
 High solubility results in ultra–short-acting drug
 High solubility results in rapid tissue redistribution
 Short-acting drugs are moderately lipid soluble
 Long-acting drugs have low lipid solubility

(Cont’d)
 Redistribution
 Drug is administered by IV
 Drug is distributed fastest to vessel-rich tissues
 Drug enters tissue based on lipid solubility
 Effect occurs when drug is in the tissue
 Drug leaves the tissue when blood level drops
• Animal recovers
 Blood carries drug to other tissues
 Drug is released by tissues and eliminated

Barbiturate Redistribution

Variations of
Barbiturate Redistribution
 Thiopental—ultra–short-acting
 Redistributed to muscle and fat and slowly
released
 Continuous or repeated dosing may lead to “full”
muscle and fat and prolonged recovery
 Methohexital—ultra–short-acting
 Redistributed to muscle and fat but released 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
 Sustained effect caused by slow uptake and
release from the brain
 Release is dependent on kidney excretion, which
is slowest
 Pentobarbital—short acting
 Brain levels decrease based on liver metabolism
 Faster than kidney excretion

Use of Barbiturates
 Rapid anesthetic induction
 To allow intubation (thiopental and methohexital)
 Sustain with inhalation anesthetic (thiopental)
 Sustain with repeated doses or continuous
infusion (methohexital)
 Use alone for short procedures
 Always intubate

Effects of Barbiturates
 CNS
 Mild sedation to unconsciousness
 Possibly excitement at low dose
 Cardiac depression
 Thiopental
• Autonomic nervous system imbalances
• Increased cardiac sensitivity to epinephrine
• Cardiac arrhythmias

Effects of Barbiturates (Cont’d)
 Decreased respiratory rate and tidal volume
 Brief apnea (thiopental)
 Shallow breaths (pentobarbital)
• Respiratory acidosis
• Poor tissue oxygenation

Other Effects of Barbiturates
 Sneezing, larynospasm, coughing
 Due to salivation
 Prevent with anticholinergics
 Initial decreased GI motility
 Later increased GI motility
 Incomplete muscle relaxation

Adverse Effects of Barbiturates
 Cardiac arrhythmia with VPCs
 Bigeminy
 Minimize with slow administration and dilute
concentration
 Preoxygenization—3-5 minutes
 “Bag” the patient two or three times after
intubation

Adverse Effects of Barbiturates
(Cont’d)
 Related to dose and rate of administration
 Initial apnea (<1-2 minutes)
 Neonate respiratory depression
• C-section using barbiturates

Other Adverse Effects of Barbiturates
 Exaggerated potency in sighthounds, critically
ill patients, hypoproteinemic or acidotic
patients
 Tissue irritation and sloughs
 Perivascular injection
 Treat with saline, with or without lidocaine
 Use dilute barbiturate solutions
 Intraarterial injection
 Thiopental
 Vasoconstriction, pain, tissue necrosis

Excitement During Induction
 Perivascular injection
 Very slow rate of administration
 Stage II excitement
 Insufficient concentration in brain to induce
Stage III
 Administer more drug

Excitement During Recovery
 Pentobarbital
 Paddling and vocalization
 IV diazepam
 Preanesthetic medications

Barbiturate-Drug Interactions
 Enhance muscle relaxants
 Increase hepatic enzyme activity
 Prolonged use
 Shorter duration of activity of drugs metabolized in
the liver
• Opioids and diazepam
 Administration with chloramphenicol
• Enhanced effects of pentobarbital and phenobarbital

Thiopental
 Ultra–short-acting
 Small animals and horses
 Rapid onset, but brief duration of action
 Complete recovery in 1-2 hours
 Crystalline powder in multidose vials
 Reconstitute with sterile water, normal saline, or
5% dextrose in water
 2.0-2.5% solution (small animals)
 5% solution (horses)
 Shelf life: 1 week refrigerated or 3 days at room
temperature
 Don’t use if a precipitate is present

Thiopental (Cont’d)
 Dose
 Varies with protocol and procedure
 Reduced up to 80% in debilitated animals
 Reduce dose in heavily sedated animals
 Give to effect
 Repeat doses are cumulative leading to prolonged
recovery
 Don’t use for anesthetic maintenance
 Various protocols for administration

Methohexital
 Ultra–short-acting
 Similar to thiopental
 Can be useful on an unfasted animal
 Rapid induction and intubation
 Decreased risk of vomitus aspiration
 A powder that must be reconstituted (sterile
water)
 1-2.5% solution (small animals)
 Shelf life—6 weeks without refrigeration
 More expensive than thiopental

Methohexital (Cont’d)
 Dosage
 1/2 to 1/3 calculated dose IV over 10 seconds
 Should allow intubation
 Give needed additional drug within 30 seconds
 Can be used in sighthounds
 Can cause profound respiratory depression
 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
 Used to treat status epilepticus
 Largely replaced with propofol
 Administered IP to rodents for general
anesthesia
 Status epilepticus
 Administer IV to stop seizure and produce heavy
sedation
 Narrow margin of safety

Pentobarbital (Cont’d)
 Provided as a 5% solution
 Onset of action 30-60 seconds IV
 Initially unable to raise head
 Jaw and tongue relaxed; pedal reflex is present
 Pedal reflex absent—intubate and provide
respiratory support
 Duration of action
 30 minutes to 2 hours
 Repeated doses can be given
• Recovery time may be prolonged with associated
excitement

Propofol
 Ultra–short-acting, nonbarbiturate anesthetic
 IV for anesthetic induction and short-term
maintenance
 Small animals, small ruminants, exotic
animals, neonates of all species
 Other use
 IV bolus and CRI to treat status epilepticus in dogs
and cats

Propofol (Cont’d)
 Minimally water soluble
 Available in an egg lecithin/glycerine/soybean
oil aqueous solution—10 mg/mL
 Milky appearance—OK to give IV
 Unknown how it affects GABA receptors
 Highly fat soluble
 Onset of action—30-60 seconds
 Duration of action—5-10 minutes
 Complete recovery
 20 minutes—dogs 30 minutes—cats

Effects of Propofol
 CNS
 Dose-dependent depression from sedation to
general anesthesia
 No analgesia
 Cardiac depressant
 Transient hypotension
 Depressant with possible apnea
 Administer slowly to effect
 Monitor patient carefully

Other Effects of Propofol
 Twitching during induction—dogs
 Muscle relaxation
 Safe to use in animals with liver disease or
kidney disease
 Appetite stimulant (low dose)
 Antiemetic
 Decreases intraocular and intracranial
pressure

Adverse Effects of Propofol
 CNS
 Transient excitement and muscle tremors
(induction)
 Paddling, muscle twitching, nystagmus,
opisthotonus (resembles seizures)
 Hypotension—transient
 Apnea (rapid injection; high dose)
• Intubation if necessary

Other Adverse Effects of Propofol
 Seizure-like signs (induction)
 Treat with diazepam
 Pain with IV injection
 Perivascular injection does not produce tissue
damage
 Cats with repeat doses
 Heinz body formation on red blood cells (RBCs)
 Diarrhea and anorexia
 Prolonged recoveries
 Sighthounds—prolonged recovery
 Also other breeds
 If maintained on propofol >30 minutes

Use of Propofol
 IV slowly over 1-2 minutes to effect
 IM produces mild sedation and ataxia only
 Dose depends on premedications
 Highly protein bound
 Don’t use in hypoproteinemic animals
 May cause excitement if given too slowly

Use of Propofol (Cont’d)
 Administration
 Boluses repeated every 3-5 minutes for 20 minutes
 CRI with syringe pump or through IV line
• Can maintain anesthesia for several hours
• Use a low dose
• Can control depth of anesthesia
 Recovery
 Dogs—complete in 20 minutes Cats—in 30 minutes
 Premedication with tranquilizers
 Decrease propofol dose
 Facilitates IV injection in unruly animals

Propofol Handling and Storage
 Poor storage characteristics
 Egg lecithin, glycerol, and soybean oil support
bacterial growth
 Use aseptic technique
 Discard unused drug within 6 hours of opening
 3-year shelf life if unopened
 more expensive than ketamine-diazepam or
thiopental

Dissociative Anesthetics
 Phencyclidine and ketamine hydrochloride
 Only ketamine is used in veterinary medicine
 Used alone
 Cats—for minor procedures or to facilitate restraint
 Used with other drugs
 Tranquilizers and opioids to induce general
anesthesia
 Subanesthetic dose
 CRI for analgesia

Dissociative Anesthetics (Cont’d)
 Tiletamine hydrochloride
 Combined with benzodiazepine zolazepam
 Telazol®
 IM or IV to produce sedation and anesthesia
 Used alone or in combination with other drugs
 A controlled substance

Mode of Action
 Disrupts nerve transmission in some brain
sections
 Selective stimulation in parts of the brain
 Decreases windup through NMDA inhibition
 Trancelike state
 Animal appears awake
 Immobile and unaware of surroundings

Dissociative Anesthetic Trancelike
State

Ketamine
 Peak action
 1-2 minutes after IV injection
 10 minutes after IM injection
 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

Dissociative Effects on the CNS
 Cataleptoid state
 Intact reflexes
 Palpebral, corneal, pedal, PLR, laryngeal,
swallowing
 Ocular effects
 Eyes remain open
 Central dilated pupil
 Use ophthalmic ointment

Dissociative Effects on the CNS
(Cont’d)
 Muscle tone
 Normal to muscle rigidity
 Counteract with concurrent tranquilizer
 Analgesia
 Somatic analgesia
 Visceral analgesia
 Amnesia (humans)
 Sensitivity to sensory stimuli

Dissociative Effects
on the Cardiovascular System
 Increase in heart rate
 Increased cardiac output
 Increased mean blood pressure
 Effects due to stimulation of the SNS

Dissociative Effects on the
Respiratory System
 Respiratory rate and tidal volume may
change
 Respiratory depression usually insignificant
 Apneustic respiration at higher doses

Adverse Effects of Dissociatives
on the CNS
 Response to sensory stimulation
 Avoid in animals with seizure disorders
 Avoid in animals that have ingested CNS
stimulants
 Avoid in animals undergoing neurological
system procedures
 Hallucinations and personal injury
 Personality change
 Nystagmus

on the Cardiovascular System
 Decreased inotropy
 Cardiac arrhythmias in response to
epinephrine release
 Screen patients for preexisting heart disease

 Respiratory depression
 Respiratory arrest
 Significantly increased salivation and
respiratory tract secretions
 Aspiration
on the Cardiovascular System (Cont’d)

Other Adverse Effects of
Dissociatives
 Pain after IM injection due to tissue irritation
 Increased intracranial and intraocular
pressure

Use of Dissociative Anesthetics
 Administration: IM or IV
 Useful in cats and horses
 Used in combination with tranquilizers
 Short procedures
 Anesthetic induction for intubation
 Chemical restraint—cats
 Immobilization—large and exotic animals
 Pain control
 No effective reversal agent

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)
 Rapid onset of action—high lipid solubility
 Administer IV or IM or orally (cats)

Ketamine (Cont’d)
 Avoid repeated injections
 Recovery in 2-6 hours
 Elimination
 Hepatic metabolism—dogs
 Renal metabolism—cats
 Often used in combination with tranquilizers

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
 Onset of action—30-90 seconds
 Duration of action—5-10 minutes
 Recovery—30-60 minutes
 Alternative combination for IM injection:
midazolam and ketamine

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
 Can be used in combination with other
tranquilizers or with ketamine
• Possible long and difficult recoveries
• Metabolized in liver and excreted via the kidneys

Advantages of Telazol®
(as compared to Ketamine)
 Decreased apneustic respiratory response
 Can be administered SC
 Used effectively in some wildlife

Etomidate
 Noncontrolled, sedative-hypnotic imidazole
drug
 Used for induction—dogs, cats, exotics
 Minimal effects on the cardiovascular and
respiratory systems
 Expensive
 Pain with IV injection
 Nausea and vomiting possible

Etomidate Mode of Action
 Similar to barbiturates and propofol
 Increased GABA inhibitory action
 Short duration of action
 Rapid redistribution away from brain
 Rapid metabolism

Etomidate Effects on the CNS
 Hypnosis
 Very little analgesia
 Decreased brain oxygen consumption
 Brain perfusion maintained
 Anticonvulsant

Effects of Etomidate
 CNS
 Initial hypotension
 Heart rate, rhythm, blood pressure, and cardiac
output minimally affected
 Initial apnea
 Crosses placental barrier
 Musculoskeletal system
 Spontaneous muscle twitching and movement

Adverse Effects of Etomidate
 Painful IV injection
 Perivascular sterile abscesses
 Hemolysis with rapid administration (cats)
 Decreased adrenal cortex function
 Decreased cortisol levels
 Nausea, vomiting, involuntary excitement
during induction and recovery

Use of Etomidate
 IV administration
 Premedicate with opioid or diazepam
 Premedicate with dexamethasone
 Repeated boluses to maintain anesthesia

Guaifenesin (GG)
 Previous name—glyceryl guaiacolate ether
(GGE)
 Noncontrolled muscle relaxant
 Common use in large animals
 Facilitate intubation
 Ease induction and recovery
 Not an anesthetic or an analgesic
 Mode of action is not understood

Effects of Guaifenesin
 Skeletal muscle relaxation
 Minimal effect on diaphragm
 Minimal effect on the cardiovascular and
respiratory systems

Adverse Effects of Guaifenesin
 Few adverse effects at therapeutic doses
 Overdose
 Muscle rigidity
 Apneustic respiration
 Perivascular tissue irritation
 Hemolysis (ruminants and horses) in high
concentrations

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
 Administered IV rapidly until animal is ataxic
 Following premedication
 Induce when patient is ataxic
 Smooth recovery

Use of Guaifenesin (Cont’d)
 Not a sedative or analgesic
 Must premedicate
 May cause excitement if there is no premedication
 Increased risk of side effects if there is no
premedication

Inhalation Anesthetics
 Classes of inhalation anesthetics
 Isoflurane and sevoflurane (halogenated
compounds)
 Nitrous oxide and desflurane
 Enflurane
 Halothane
 Methoxyflurane
 Diethyl ether

Diethyl Ether
 No longer used as an anesthetic agent
 Classic stages and planes of anesthesia
described using ether
 Desirable characteristics
 Stable cardiac output, rhythm, and blood pressure
 Stable respirations
 Good muscle relaxation

Diethyl Ether (Cont’d)
 Undesirable characteristics
 Tracheal and bronchial mucosal irritation
 Prolonged induction and recovery
 Postoperative nausea and vomiting
 Flammable and explosive

Halogenated Organic Compounds
 Isoflurane and sevoflurane are the most
commonly used agents in this class
 Liquid at room temperature
 Stored in a vaporizer on an anesthetic
machine
 Vaporized in oxygen that flows through the
vaporizer

Uptake and Distribution of
 Liquid anesthetic is vaporized and mixed with
oxygen gas
 Mixture is delivered to the patient via a mask
or endotracheal tube (ET tube)
 Mixture travels to lungs (alveoli) and diffuses
into the bloodstream
 Diffusion rate is dependent on concentration
gradient (alveoli/capillary) and lipid solubility
 Concentration gradient is greatest during
initial induction

Uptake and Distribution of Halogenated
Organic Compounds (Cont’d)
 Distribution to tissues is dependent on blood supply
 Lipid solubility determines entry into tissues through cell
walls
 Depth of anesthesia is dependent on partial pressure
of anesthetic in the brain
 Partial pressure in the brain is dependent on partial pressure
of the anesthetic in blood and alveoli
 Maintenance of anesthesia is dependent on sufficient
quantities of anesthetic delivered to the lungs

Elimination of
 Reducing amount of anesthetic administered reduces
amount delivered to the alveoli
 Blood level is initially higher than alveolar level
 Concentration gradient now favors anesthetic
diffusion from blood into the alveoli
 Blood levels drop quickly as patient breathes out
anesthetic from the alveoli
 Brain levels drop as less anesthetic is delivered by
blood
 Patient wakes up

Effects of
 CNS
 Dose-related reversible CNS depression
 Hypothermia
 Depress cardiovascular function
 Effects on HR variable
 Dose-dependent ventilation depression

Adverse Effects of
 CNS (Cont’d)
 Increased intracranial pressure in patients with
head trauma or brain tumors
 Considered safe for epileptic animals
 Decrease blood pressure and may decrease renal
blood flow
 Hypoventilation
 Carbon dioxide retention and respiratory acidosis

Physical and Chemical Properties
of Inhalant Anesthetics
 Important properties to consider
 Vapor pressure
 Partition coefficient
 Minimum alveolar concentration (MAC)
 Rubber solubility

Vapor Pressure
 The tendency of an inhalation anesthetic to
vaporize to its gaseous state
 Determines how readily an inhalation
anesthetic will evaporate in the anesthetic
machine vaporizer
 Temperature and anesthetic agent dependent

Vapor Pressure (Cont’d)
 Volatile agents
 High vapor pressure
 Isoflurane, sevoflurane, desflurane, and halothane
 Delivered from a precision vaporizer to control the
delivery concentration
 All precision vaporizers are made to deliver only
one specific halogenated agent
 Nonvolatile agents
 Low vapor pressure
 Methoxyflurane
 Delivered from a nonprecision vaporizer

Blood:Gas Partition Coefficient
 The measure of the solubility of an inhalation
anesthetic in blood as compared to alveolar
gas (air)
 Indication of the speed of induction and
recovery for an inhalation anesthetic agent
 Low blood:gas partition coefficient
 Agent is more soluble in alveolar gas than in blood
at equilibrium
 Agent is less soluble in blood
 Faster expected induction and recovery

(Cont’d)
 High blood:gas partition coefficient
 Agent is more soluble in blood than in alveolar gas
at equilibrium
 Agent is less soluble in alveolar gas
 Agent is absorbed into blood and tissues (sponge
effect)
 Slower expected induction and recovery

(Cont’d)
 Blood: gas partition coefficient determines the
clinical use of the anesthetic agent
 Induction: Can a mask be used?
 Maintenance: How fast will the anesthetic depth
change in response to changes in the vaporizer
setting?
 Recovery: How long will the patient sleep after
anesthesia?

Minimum Alveolar Concentration
(MAC)
 The measure of the potency of a drug
 Used to determine the average setting on the
vaporizer that will produce surgical anesthesia
 The lower the MAC, the more potent the
anesthetic agent and the lower the vaporizer
setting
 MAC may be altered by age, metabolic activity,
body temperature, disease, pregnancy, obesity,
and other agents present
 Every patient must be monitored as an
individual

Isoflurane
 Most commonly used inhalant agent in North
America
 Approved for use in dogs and horses;
commonly used in other species

Isoflurane (Cont’d)
 Properties
 High vapor pressure: need a precision vaporizer
 Low blood:gas partition coefficient: rapid induction
and recovery
 Good for induction with mask or chamber
 MAC = 1.3% to 1.63%: helps determine initial
vaporizer setting
 Low rubber solubility
 Stable at room temperature; no preservatives
needed

Effects and Adverse Effects of
Isoflurane
 Maintains cardiac output, heart rate, and rhythm
 Fewest adverse cardiovascular effects
 Depresses the respiratory system
 Maintains cerebral blood flow
 Almost completely eliminated through the lungs
 Induces adequate to good muscle relaxation
 Provides little or no analgesia after anesthesia
 Can produce carbon monoxide when exposed to a
desiccated carbon dioxide absorbent

Sevoflurane
 High vapor pressure: need a precision
vaporizer
 Blood:gas partition coefficient: rapid induction
and recovery
 Good for induction with a mask or chamber
 High controllability of depth of anesthesia
 MAC = 2.34% to 2.58%

Sevoflurane
 Minimal cardiovascular depression
 Depresses respiratory system
 Eliminated by the lungs, minimal hepatic
metabolism
 Maintains cerebral blood flow
 Induces adequate muscle relaxation
 Some paddling and excitement during
recovery

Desflurane
 Closely related to isoflurane
 Expensive
 Lowest blood:gas partition coefficient: very
rapid induction and recovery
 Used with a special precision vaporizer
 MAC = 7.2% and 9.8%
 Least potent inhalant agent
 Eliminated by the lungs

Desflurane
 Strong vapors cause coughing and holding
the breath
 Other effects are similar to isoflurane
 Transient increase in heart rate and blood
pressure (humans)

Other Halogenated Inhalation Agents
 Halothane (Fluothane)
 Not commonly used anymore
 Being replaced by isoflurane and sevoflurane
 Methoxyflurane
 No longer available in North America
 Enflurane
 Used primarily in human medicine
 Nitrous oxide
 Used primarily in human medicine; some veterinary use
 A gas at room temperature; no vaporizer is required

CNS and Respiratory Stimulants
 Doxapram
 Analeptic agent
 Stimulates respiration and speeds recovery
 Used in neonate puppies and kittens after C-
section
 IV administration or sublingual drops (neonates)

Adverse Effects of Doxapram
 Lowers seizure threshold
 CNS damage

Use of Doxapram
 Repeat injections may be necessary
 Reverses respiratory depression from
inhalant agents and barbiturates

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