1 / 16

BARBITURATES

BARBITURATES. DENNIS STEVENS MSN, CRNA, ARNP NOVEMBER 2005 FLORIDA INTERNATIONAL UNIVERSITY PHARMACOLOGY OF ANESTHESIOLOGY NURSING NGR 6173. OBJECTIVES. Discuss the preparation of barbiturates regarding expiration times following reconstitution.

liam
Télécharger la présentation

BARBITURATES

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. BARBITURATES DENNIS STEVENS MSN, CRNA, ARNP NOVEMBER 2005 FLORIDA INTERNATIONAL UNIVERSITY PHARMACOLOGY OF ANESTHESIOLOGY NURSING NGR 6173

  2. OBJECTIVES • Discuss the preparation of barbiturates regarding expiration times following reconstitution. • Compare the structure-activity relationships of oxybarbiturates and thiobarbiturates. • Explain mechanism of action associated with barbiturates and involvement with neurotransmitters. • Discuss the pharmacokinetic properties specific to barbiturates. • Explain the effects that barbiturates have on organ systems. • State potential drug interactions with barbiturates.

  3. REFERENCES Morgan, G.E., Mikhail, M.S., and Murray, M.J. (2002). Clinical Anesthesiology. (3rd Ed.) New York, NY: McGraw-Hill. Nagelhout, J.J. and Zaglaniczny, K.L. (2005). Nurse Anesthesia. (3rd Ed.) St. Louis, MO: Elsevier- Saunders. Stoelting, R.K. (1999). Pharmacology & Physiology in Anesthesia Practice. (3rd Ed.) Philadelphia, PA: J.B. Lippincott Company.

  4. COMMERCIAL PREPARATIONS • Barbiturates are prepared commercially as sodium salts readily soluble in water or saline • These highly alkaline solutions are incompatible for mixture with many medications which are acidic • Thiopental usually prepared in 2.5% solution • Methohexital usually prepared in 1% solution • Powder form of thiopental stable indefinitely • Refrigerated solutions: • Thiobarbiturates stable up to two weeks • Methohexital stable up to six weeks • Room temperature reconstituted solutions of thiopental remain stable and sterile for at least 6 days

  5. BARBITURATES

  6. STRUCTURE ACTIVITY RELATIONSHIPS • Barbiturates are barbituric acid derivatives • Barbiturates with sedative-hypnotic properties result from substitutions at the number 2 and 5 carbon atoms of barbituric acid • Substitutions determine hypnotic potency, lipid solubility, anticonvulsant properties, onset, and duration of action • Barbiturates that retain: • An oxygen atom on number two carbon are designated as oxybarbiturates • A sulfur atom on number two carbon results in thiobarbiturates

  7. MECHANISM OF ACTION • Barbiturates depress the RAS (reticular activating system) • Preferentially affect the function of nerve synapses rather than axons • Suppress transmission of excitatory neurotransmitters • Enhance transmission of inhibitory neurotransmitters • Interferes with transmitter release (presynaptic) and stereoselectively interacting with receptors (postsynaptic)

  8. PHARMACOKINETICSCLINICAL CONSIDERATIONS • Prompt awakening after a single dose of thiopental or methohexital reflects redistribution of these drugs from brain to inactive tissues • Elimination from the body depends almost entirely on metabolism

  9. PHARMACOKINETICSABSORPTION AND DISTRIBUTION • Barbiturates are most frequently administered intravenously for induction of general anesthesia in adults and children with an established IV • Exceptions: • Rectal methohexital for induction in children • Distribution of barbiturates in the body is determined by lipid solubility, protein binding, and degree of ionization • Tissue blood flow is major determinant in delivery of barbiturates to tissues • Duration of action of highly lipid-soluble barbiturates determined by redistribution

  10. PHARMACOKINETICSBIOTRANSFORMATION AND EXCRETION • Metabolism of barbiturates principally involves hepatic oxidation to inactive water-soluble metabolites • Thiobarbiturates also break down to a small extent in extrahepatic sites • Hepatic dysfunction • Renal excretion is limited to water-soluble end products of hepatic biotransformation • <1% of administered thiopental or methohexital is excreted unchanged in the urine • Elimination half-time: • Thiopental - 11.6 hrs • Methohexital – 3.9 hrs

  11. CLINICAL INDICATIONS • Principal clinical uses of barbiturates: • Induction of anesthesia • Treatment of increased intracranial pressure • Barbiturates have been replaced by benzodiazepines for preanesthetic medication • Rapid onset of action of barbiturates renders these drugs useful for treatment of grand mal seizures, but benzodiazepines are probably superior

  12. CLINICAL INDICATIONS • Thiopental: • Induction dose: 3-5 mg/Kg IV • Metabolism and redistribution to inactive tissue sites are important determinants of early awakening • Metabolized in the liver to metabolites that are more water soluble and have little CNS activity • Methohexital: • Induction dose: 1-1.5 mg/Kg IV or 25 mg/Kg PR • Metabolized more rapidly than thiopental reflecting lesser lipid solubility • Redistribution to inactive tissue sites

  13. EFFECTS ON ORGAN SYSTEMS • Cardiovascular: • IV induction dose causes a fall in BP and a rise in HR • CO often maintained by a rise in HR and increased myocardial contractility • CV effects of barbiturates vary markedly, depending on volume status, baseline autonomic tone, and preexisting cardiovascular disease • Consider slow rate of injection and adequate preoperative hydration • Respiratory: • Decreased response to hypercapnia and hypoxia • Leads to upper airway obstruction and apnea • During awakening TV and RR decreased

  14. EFFECTS ON ORGAN SYSTEMS • Cerebral: • Decreases cerebral blood flow and ICP • Cerebral perfusion pressure usually increased • Cerebral oxygen consumption decreased • EEG activity changes: Low-voltage fast activity- small dose High-voltage slow activity to electrical silence- large dose • Taste sensation during induction with thiopental • Barbiturates appear to have an antianalgesic effect • Grand mal seizures: • Thiopental 50-100 mg IV

  15. EFFECTS ON ORGAN SYSTEMS • Renal: • Reduce RBF and GFR in proportion to fall in BP • Hepatic: • Hepatic blood flow is modestly decreased • Induction doses do not alter postoperative LFTs • Placental Transfer: • Maternal doses of thiopental up to 4 mg/Kg IV probably do not result in excessive concentrations of barbiturates in fetal brain • Immunologic: • Anaphylactic and anaphylactoid reactions are rare • Treatment of allergic reaction • Some evoke mast cell histamine release

  16. MEDICATION INTERACTIONS • Contrast media, sulfonamides, and other drugs that occupy the same protein-binding sites as thiopental will increase the amount of free drug available • ETOH, narcotics, antihistamines, and other CNS depressants potentiate the sedative effects of barbiturates • Chronic ETOH abuse

More Related