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General Veterinary Anesthesia

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

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  1. General Veterinary Anesthesia Joanna Webb CHEM 5398 Spring 2010

  2. Outline • History of Anesthesia • Methods of Administration • Mechanisms of Action • Companion Animal Drugs

  3. Goals of Anesthesia • Amnesia • Loss of memory • Immobility • Stay still • Analgesia • Pain relief • Homeostasis

  4. Timeline Blaze ppt. TCSVM

  5. Methods of Administration Common: Inhalation Intravenous Intramuscular Less Common: Rectal Oral Nasal Intraperitoneal

  6. 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

  7. 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

  8. Action Potentials: Overview • Ach is a main neurotransmitter of the autonomic NS of PNS • In the CNS, excitatory actions

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

  10. 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

  11. 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

  12. 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

  13. 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

  14. 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

  15. 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

  16. 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

  17. 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

  18. 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

  19. 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 (-)

  20. 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

  21. 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

  22. 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>

  23. Assigned Reading • Goodman and Gilman’s Pharmacological Basis of Therapeutics, Chapter 13, pp. 341-363

  24. 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.

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