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Final

  1. 1. Halothane and Sevoflurane Verna Thomas, RN, BSN, SRNA Leah Baumgardner, RN, BSN, SRNATuesday, March 26, 13
  2. 2. Halothane History Initially introduced in the mid 1950’s Halothane became the most widely used inhalational anesthetic. Today, its prevalence in modern medicine has diminished to use in Third World countries and veterinary surgery. The arrival of safer anesthetics and better pharmocokinetics in the 1980’s and 1990’s was a substantial contributor to its elimination in American medicine.Tuesday, March 26, 13
  3. 3. Halothane Functional Group 2-bromo-2-chloro-1,1,1,triflouroethaneTuesday, March 26, 13
  4. 4. Halothane MetabolismTuesday, March 26, 13
  5. 5. Halothane Halothane Sevoflurane HALOTHANE HEPATITIS Boiling Point (°C) 50.2 58.5 Type I (mild): Benign hepatotoxicity, Vapor Pressure @ 20°C (mmHg) 243 120 transient ↑ in serum transaminase Molecular Weight (Da) 197.4 200 and glutathione S-transferase Specific Gravity (g/mL) 1.87 1.50 concentrations, no jaundice or Blood:Gas Partition Coefficient 2.4 0.66 hepatocellular disease evident. Oil:Gas Partition Coefficient 224 53.4 Type II (fulminant halothane MAC (vol%) 0.75 2.05 hepatitis): Massive centrilobular liver Metabolism (% approx) 20 5 necrosis, 50% mortality, fever, jaundice, and marked ↑↑serum transaminase levels, immune Cardiac: ↓BP, ↓HR, ↓CO mediated. Respiratory: ↓VT, ↑RR, ↑PaCO2 Cerebral: ↑CBF, ↑ICP, ↓cerebral metabolic rate, ↓seizures Renal: ↓GFR, ↓renal blood flow, ↓UO Hepatic: ↓hepatic blood flowTuesday, March 26, 13
  6. 6. Sevoflurane Inhalation Anesthetic Use: Induction and maintenance of general anesthesia Adult and Pediatric Effects on Organ Systems: Cardiac: moderate reduction in SVR and MAP but myocardial contractility and heart rate unchanged Respiratory depressant but most effective bronchodilator and least irritant of the inhaled anesthetics Relaxes Muscles and attenuates response to noxious stimuli Causes less cerebral vasodilatation and maintains cerebral autoregulation well Contraindications: Malignant HyperthermiaTuesday, March 26, 13
  7. 7. Sevoflurane Naming: Functional Group ETHER: R-O-R IUPAC : 1,1,1,3,3,3,-Hexafluoro-2-(fluoromethoxy)-propane Molecular Formula: C4H3F7OTuesday, March 26, 13
  8. 8. Sevoflurane PROPERTIES STRUCTURE: Non-polar more polar than alkanes (because of Oxygen) but less polar than alcohols Very slightly water soluable HALOGENATED: with Flourine BOILING POINT: Low - 58.5 degrees Celsius ODOR: PleasantTuesday, March 26, 13
  9. 9. Sevoflurane Oil/gas partition coefficient: 47.2 MAC (Vol%) [in patients aged 30-60y]: 2.05 Blood/gas partition coefficient: 0.69 - low solubility in the blood results in rapid induction, improved control of depth of anesthesia, and fast emergence/ recovery pKa (Acidic and Basic) are not provided but PubChem lists H-Bond Donor: 0 H-Bond Acceptor: 8Tuesday, March 26, 13
  10. 10. Sevoflurane Metabolism 95-98% is eliminated through the lungs - rapidly because of low blood/gas solubility The remaining 2-5% is metabolized... Cytochrome P450 System - LIVER - defluorinated to hexaflouroisopropanol (HFIP) with release of inorganic flouride and carbon dioxide - HFIP conjugated with glucuronic acid to HFIP-glucuronide and excreted in the urineTuesday, March 26, 13
  11. 11. Sevoflurane Degradation- in the presence of CO2 absorbents used inanesthesia circuits i.e. Baralyme or soda limeLoss of Hydrogen Fluoride produces Compound Afluoromethyl-2,2-difluoro- 1- (trifluoromethyl)vinyl ether (CF2 = C(CF3) OCH2F)Compound A has been shown to be nephrotoxicin rats but not shown in humans- dose related proteinuria, glycosuria, andenzymuriaReduce amount of Compound A by using fresh gasinflows >2L/minTuesday, March 26, 13
  12. 12. Sevoflurane 1. Formation of Compound A is directly/inversely proportional to fresh gas inflow??? 2. What characteristic of Sevoflurane is responsible for rapid induction and rapid elimination??Tuesday, March 26, 13
  13. 13. ReferencesTuesday, March 26, 13
  14. 14. References Behne, M., Wilke, H. J., & Harder, S. (1999). Clinical pharmacokinetics of sevoflurane. Clinical pharmacokinetics, 36(1), 13-26. Eger II, E. I. (1991). Metabolism of Sevoflurane. Anesthesia & Analgesia, 73(5), 671-671. Hemmings, H. C., & Hopkins, P. M. (2006). Foundations of anesthesia: basic sciences for clinical practice. Mosby Incorporated. Sevoflurane. In (2012). Drugs.com. Retrieved from http://www.drugs.com/pro/sevoflurane.htmlTuesday, March 26, 13

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