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General Veterinary Anesthesia. Joanna Webb CHEM 5398 Spring 2010. Outline. History of Anesthesia Methods of Administration Mechanisms of Action Companion Animal Drugs. Goals of Anesthesia. Amnesia Loss of memory Immobility Stay still Analgesia Pain relief Homeostasis . Timeline.

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general veterinary anesthesia

General Veterinary Anesthesia

Joanna Webb

CHEM 5398

Spring 2010

outline
Outline
  • History of Anesthesia
  • Methods of Administration
  • Mechanisms of Action
  • Companion Animal Drugs
goals of anesthesia
Goals of Anesthesia
  • Amnesia
    • Loss of memory
  • Immobility
    • Stay still
  • Analgesia
    • Pain relief
  • Homeostasis
timeline
Timeline

Blaze ppt. TCSVM

methods of administration
Methods of Administration

Common: Inhalation

Intravenous

Intramuscular

Less Common:

Rectal

Oral

Nasal

Intraperitoneal

meyer overton rule
Meyer-Overton Rule
  • Used to think all anesthetics worked the same way
  • The gas disrupted cell membrane lipids
  • Flaw: enantiomers of the same anesthetic have unique actions but the same physical properties (i.e. isoflurane)
  • Therefore, anesthetics must bind to specific proteins
mechanism of action
Mechanism of Action
  • Hyperpolarize neurons
  • Anticholingeric: suppresses nervous system communication
  • Alpha-2 adrenergic receptor agonist/antagonist: suppress norepinephrine binding/release to receptor
  • Cardiovascular depressant
  • Respiratory depressant
action potentials overview
Action Potentials: Overview
  • Ach is a main neurotransmitter of the autonomic NS of PNS
  • In the CNS, excitatory actions
anesthesia induction
Anesthesia Induction

http://www.youtube.com/watch?v=VByEDXsRIFI&feature=related

inhalation anesthetics
Inhalation Anesthetics
  • Diethyl ether, nitrous oxide, chloroform
  • Halothane
  • Isoflurane
  • Sevoflurane

http://www.dreveterinary.com/catalog/images/coaxial_lg_5.jpg

http://www.asbestos.co.za/images/alveoli.jpg

diethyl ether
Diethyl ether
  • First anesthetic discovered
  • Nontoxic to organs
  • Unpleasant smell
  • Decreases possibility of action potential by decreasing rate of rise to an end-plate potential
chloroform ch cl 3
Chloroform CH(Cl)3
  • Colorless and odorless
  • Hepatotoxin
  • Severe CV depressant
    • Cardiac arrhythemia
    • Aka Sudden Sniffer’s Death
  • Blocks flow of K+ out of the cell

www.inchem.org/documents/ehc/ehc/ehc163.htm

isoflurane
Isoflurane
  • Binds to GABA receptor: enhances inhibitory synapses
    • Lets more Cl- into the cell
  • Competitive glycine inhibitor: agonist for N-methyl-D-aspartic acid (NMDA) receptor
  • Pre-medicate with a barbiturate
  • Dog: 2.0-2.5% isoflurane concentration (in oxygen)
  • Horse: 3.0-5.0% isoflurane concentration (in oxygen)
  • Can keep it on a low concentration throughout the procedure
sevoflurane
Sevoflurane
  • Newer, more expensive than isoflurane
  • Dogs: Induce with 7.0% sevoflurane
  • Maintenance level is 3.3-3.6% with pre-medication
  • 3.7-4.0% maintenance concentration without pre-medication
  • Common pre-meds: benzodiazepine or phenothiazine
  • Isoflurane is safer because patient does not require as much anesthesia, can be kept lighter
    • Higher cardiovascular stability
injectable anesthetics
Injectable anesthetics

Pre-anesthetics

Induction anesthetics

Dissociative

Ketamine

Tiletamine

Benzodiazepines

Diazepam

Zolazepam

Propofol

Barbiturates

  • Mild sedative, analgesic
  • Acepromazine
    • Combine with NSAID or opiod
  • Medetomidine
  • Atipamezole
pharmacokinetics of injectable anesthetics
Pharmacokinetics of Injectable Anesthetics
  • Partition into the highly lipophilic tissues of the brain and spinal cord
  • Produce rapid anesthesia
  • Immediate low concentrations of anesthetic in blood stream causes the drug to leave the CNS and enter the peripheral tissues via the blood
  • Effect can wear off in about 10 minutes unless continuously infused
acepromazine combination
Acepromazine Combination
  • Ace is provides strong sedation and antiemetic effects
  • Phenothiazine
  • Give with a NSAID or opiod to provide anagesic effects
  • 6-8 hours of activity
  • Anticholinergic, antihistamine, antispasmodic, and alpha-andrenergic blocking
acepromazine combination continued
Acepromazine Combination Continued
  • Medetomidine is an NSAID
    • Strong sedative, strong analgesic
    • Alpha-2 adrenergic receptor agonist
    • 45-90 minutes
  • Atipamezole
    • Reversal agent
    • Alpha-2 adrenergic receptor antagonist
    • Administer a new analgesic after reversal since ALL effects of medetomidine are reversed

Norepinephrine

Atipamezole

Medetomidine

dissociative anesthetics
Dissociative Anesthetics
  • Ketamine inhibits excitatory synapses
    • Dissociate: cataleptic state
    • Eyes open, limb movements involuntary
      • Serotonin, dopamine
    • High analgesic effects
    • Hypnotic state
  • Increases intracranial pressure and blood flow
  • Marketed as a racemic mixture
  • Partially water soluble pKa 7.5
  • Highly lipophilic

S (+)

R (-)

benzodiazepines
Benzodiazepines
  • Alpha-2 andrenergic receptor agonist
  • Binds to GABA receptor
    • Gamma-aminobutyric acid

>20%: anxiolysis

>30-50%: sedation

>50%: unconsciousness

  • Opens Cl-channel, hyperpolarize membrane, so inhibitory
  • Given with ketamine to produce better anesthetic effects

Diazepam

barbiturates
Barbiturates
  • Pentobarbital
  • Derivative of barbituric acid (has no CNS activity)
    • Oxygen or sulfur at 2 position
    • Adds to CNS depressant activity
  • Commonly used in rats: research
  • Marketed as pentobarbital sodium powder
    • Soluble in water or alcohol, forms clear solution
  • Inhibits excitatory and enhances inhibitory CNS signals

Pentobarbital

Barbituric acid

references
References
  • http://www.metrohealthanesthesia.com/edu/ivanes/ketamine2.htm
  • http://www.inchem.org/documents/ehc/ehc/ehc163.htm
  • http://vetmed.duhs.duke.edu/guidelines_for_pentobarbital.htm
  • http://metrohealthanesthesia.com/edu/ivanes/benzos1.htm
  • Blaze, C.A. (2009). Veterinary anesthesia and analgesia introduction. Microsoft Powerpoint. Tufts Cummings School of Veterinary Medicine.
  • Chloroform. 2010). Wikipedia. Retrieved (2010, April 4) from http://en.wikipedia.org/wiki/Chloroform#Production
  • Dickinson, R, Peterson, B.K, Banks, P.B., Similis, C, Martiin, J.C.S., Valenzulela, C.A., Maze, M, Franks, N.P. (2007). Competitive inhibition at the glycine site of the N-methyl-D-aspartate receptor by the anesthetics xenon and isoflurane: evidence from molecular modeling and electrophysiology. Anesthesiology, 107(5): 756-767.
  • Muir, W.W. (2008): Intravenous anesthetic drugs: dissociative anesthetics. DVM360. Retrieved (2010, April 5)
  • End plate potentials. (2009). Wikipedia. Retrieved (2010, April 4) from http://en.wikipedia.org/wiki/End-plate_potential
  • University of Minnesota. Guidelines for the use of anesthetics, analgesics and tranquilizers in laboratory animals. Accessed 15 February 2010. < http://www.ahc.umn.edu/rar/anesthesia.html#Selection>
assigned reading
Assigned Reading
  • Goodman and Gilman’s Pharmacological Basis of Therapeutics, Chapter 13, pp. 341-363
homework questions
Homework Questions
  • Draw the structure of propofol, the most commonly used anesthetic in the US.
  • Propofol is not water soluble, thus has to be constituted in an emulsion-like mixture of soybean oil, glycerol, and egg phosphatide. Circle the structural features responsible for its water insolubility.
  • Halothane, isoflurane and sevoflurane are commonly used inhalation anesthetics. Draw their structures
  • Draw and label the R and S stereoisomers of ketamine.
  • Which stereoisomer of ketamine has more psychic emergence? Which stereoisomer contributes more analgesic and anesthetic effects?
  • Thiopental (pentobarbital), thiamylal, methohexital are all derivatives of barbituric acid. Draw their structures and that of the parent structure barbituric acid.