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Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Chapter 27 General Anesthetics
2Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. General Anesthetics General anesthetics are drugs that produce unconsciousness and lack of responsiveness to all painful stimuli Local anesthetics do not reduce consciousness, and they blunt pain only in a limited area
3Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Pain Analgesia Loss of sensibility to pain Anesthesia Loss of pain and loss of all other sensations
4Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. General Anesthetics Two main groups Inhalation anesthetics Intravenous anesthetics Before 1846 Surgery: brutal and excruciatingly painful Strong people and straps used to restrain patient Survival based on surgeon’s speed
5Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. General Anesthetics Given only by licensed anesthesiologists (physicians) and CRNAs (nurses) Used to facilitate certain procedures Endoscopy, urologic procedures, radiation therapy, electroconvulsive therapy, transbronchial biopsy, various cardiologic procedures
6Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Basic pharmacology of inhalation anesthetics Properties of individual inhalation anesthetics Intravenous anesthetics General Anesthetics
7Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Basic Pharmacology of Inhalation Anesthetics Properties of an ideal inhalation anesthetic Balance anesthesia Molecular mechanism of action Minimum alveolar concentration
8Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Pharmacokinetics Uptake and distribution Uptake From the lungs From the lungs The greater the concentration, the more rapid the uptake The greater the concentration, the more rapid the uptake Distribution To CNS and other tissues To CNS and other tissues Determined largely by regional blood flow Determined largely by regional blood flow Elimination Exported in the expired breath Inhalation anesthetics are almost entirely eliminated by the lungs Inhalation anesthetics are almost entirely eliminated by the lungs Metabolism Hepatic metabolism is minimal Hepatic metabolism is minimal
9Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Pharmacokinetics Adverse effects Respiratory and cardiac depression Sensitization of the heart to catecholamines Malignant hyperthermia Aspiration of gastric contents Toxicity to operating room personnel Hepatotoxicity
10Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Drug Interactions Analgesics, CNS depressants, and CNS stimulants can influence the amount of anesthetic required to produce anesthesia Opioids allow for a reduction CNS depressants add to the depressant effects of anesthesia
11Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Adjuncts to Inhalation Anesthesia Preanesthetic medications Given to reduce anxiety, produce perioperative amnesia, and relieve preoperative and postoperative pain Benzodiazepines Benzodiazepines Opioids Opioids Clonidine, an alpha 2 -adrenergic agonist Clonidine, an alpha 2 -adrenergic agonist Anticholinergic drugs Anticholinergic drugs
12Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Neuromuscular Blocking Agents Surgical procedures require skeletal muscle relaxation NBAs reduce amount of anesthesia needed NBAs prevent contraction of all skeletal muscles, including diaphragm and muscles of respiration (flaccid paralysis) 21 million patients undergo surgery 20,000–40,000 wake up during the procedure
13Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Postanesthetic Medications Analgesics Mild pain: aspirin-like drugs Severe pain: opioids Antiemetics Ondansetron (Zofran) Muscarinic antagonists Abdominal distention and urinary retention Bethanechol
14Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Properties of Individual Inhalation Anesthetics Halothane (no longer available in United States) Isoflurane Enflurane Desflurane Sevoflurane Nitrous oxide Obsolete inhalation anesthetics
15Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Halothane Prototype for volatile inhalation anesthetics No longer available in United States Anesthetic properties High-potency anesthetic Time course: smooth and relatively rapid Weak analgesia Muscle relaxation generally inadequate for surgery
16Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Halothane Adverse effects Hypotension Respiratory depression Requires support with oxygen-rich gas mixture Requires support with oxygen-rich gas mixture Promotion of dysrhythmias Epinephrine and catecholamines should be used with caution. Epinephrine and catecholamines should be used with caution. Malignant hyperthermia Genetically predisposed Genetically predisposed Hepatotoxicity Rare Rare Other adverse effects Elimination 60%–80% by lungs and 20% hepatic
17Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Isoflurane Most widely used inhalation anesthetic Properties much like those of halothane Better muscle relaxant, but still requires NMB Not associated with renal or hepatic toxicity
18Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Enflurane Has pharmacologic properties very similar to those of halothane Newer agents now preferred
19Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Desflurane (Suprane) Nearly identical in structure to isoflurane Induction occurs more rapidly than with any other volatile anesthetics
20Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Sevoflurane (Ultane) Similar to desflurane Approved for induction and maintenance
21Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Nitrous Oxide Also known as “laughing gas” Very low anesthetic potency Very high analgesic potency Never used as primary anesthetic Frequently combined with other inhalation agents to enhance analgesia 20% nitrous oxide = Pain relief of morphine No serious side effects (nausea and vomiting)
22Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Obsolete Inhalation Anesthetics Ethylene Cyclopropane Diethyl ether (ether) Vinyl ether Ethyl chloride Abandoned because they are explosive and offer no advantage over newer anesthetics
23Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Intravenous Anesthetics Short-acting barbiturates (thiobarbiturates) Benzodiazepines Propofol Etomidate Ketamine Neuroleptic-opioid combination: droperidol plus fentanyl
24Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Short-Acting Barbiturates (Thiobarbiturates) Administered intravenously Used for induction of anesthesia Two agents Thiopental sodium (Pentothal) Methohexital sodium (Brevital)
25Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Benzodiazepines Diazepam Induction with intravenous diazepam (Valium) Unconsciousness within a minute Very little muscle relaxation Midazolam Unconsciousness within 80 seconds Can cause dangerous cardiorespiratory effects
26Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Propofol Most widely used anesthetic Actions and uses Unconsciousness develops within 60 seconds and lasts 3–5 minutes Sedative-hypnotic for induction and maintenance of analgesia Mechanical ventilation and procedures Mechanical ventilation and procedures Adverse effects Can cause profound respiratory depression Can cause hypotension Risk of bacterial infection
27Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Propofol Risks for abuse Not a controlled substance Supplies are not closely monitored Widely available in operating rooms, etc. No “high” Instantaneous but brief sleep period Patients awaken “refreshed” and talkative, and report feeling elated and even euphoric
28Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Fospropofol Fospropofol (Lusedra) Intravenous prodrug Conversion to propofol in the lever Effects similar to propofol Slower onset of sedation (4 min vs. 1 min) Lower risk of bacteremia Schedule IV drug
29Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Etomidate Potent hypnotic agent Used for induction Repeated administration can cause hypotension, oliguria, electrolyte disturbances, and high incidence of postoperative nausea and vomiting
30Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Ketamine Anesthetic effects Dissociative anesthesia Sedation, immobility, analgesia, and amnesia Adverse psychologic reactions Hallucinations, disturbing dreams, and delirium Soothing environment Therapeutic uses Anesthesia for young children with minor procedures
31Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Neuroleptic-Opioid Combination: Droperidol Plus Fentanyl Quiescence Indifference to surroundings Patient appears to be asleep but is not in a state of complete loss of consciousness. Used for diagnostic and minor procedures Adverse effects Prolongs the QT interval, hypotension, and respiratory depression
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