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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
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Pain
Analgesia Loss of sensibility to pain
Anesthesia Loss of pain and loss of all other sensations
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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
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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
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Basic pharmacology of inhalation anesthetics Properties of individual inhalation anesthetics Intravenous anesthetics
General Anesthetics
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Basic Pharmacology of Inhalation Anesthetics
Properties of an ideal inhalation anesthetic Balance anesthesia Molecular mechanism of action Minimum alveolar concentration
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Pharmacokinetics
Uptake and distribution Uptake
• From the lungs• The greater the concentration, the more rapid the uptake
Distribution• To CNS and other tissues• Determined largely by regional blood flow
Elimination Exported in the expired breath
• Inhalation anesthetics are almost entirely eliminated by the lungs
Metabolism• Hepatic metabolism is minimal
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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
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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
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Adjuncts to Inhalation Anesthesia
Preanesthetic medications Given to reduce anxiety, produce perioperative
amnesia, and relieve preoperative and postoperative pain• Benzodiazepines• Opioids• Clonidine, an alpha2-adrenergic agonist• Anticholinergic drugs
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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
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Postanesthetic Medications
Analgesics Mild pain: aspirin-like drugs Severe pain: opioids
Antiemetics Ondansetron (Zofran)
Muscarinic antagonists Abdominal distention and urinary retention Bethanechol
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Properties of Individual Inhalation Anesthetics
Halothane (no longer available in United States)
Isoflurane Enflurane Desflurane Sevoflurane Nitrous oxide Obsolete inhalation anesthetics
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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
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Halothane Adverse effects
Hypotension Respiratory depression
• Requires support with oxygen-rich gas mixture Promotion of dysrhythmias
• Epinephrine and catecholamines should be used with caution. Malignant hyperthermia
• Genetically predisposed Hepatotoxicity
• Rare Other adverse effects
Elimination 60%–80% by lungs and 20% hepatic
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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
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Enflurane
Has pharmacologic properties very similar to those of halothane
Newer agents now preferred
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Desflurane (Suprane)
Nearly identical in structure to isoflurane Induction occurs more rapidly than with any
other volatile anesthetics
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Sevoflurane (Ultane)
Similar to desflurane Approved for induction and maintenance
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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)
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Obsolete Inhalation Anesthetics
Ethylene Cyclopropane Diethyl ether (ether) Vinyl ether Ethyl chloride Abandoned because they are explosive and
offer no advantage over newer anesthetics
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Intravenous Anesthetics
Short-acting barbiturates (thiobarbiturates) Benzodiazepines Propofol Etomidate Ketamine Neuroleptic-opioid combination: droperidol
plus fentanyl
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Short-Acting Barbiturates (Thiobarbiturates)
Administered intravenously Used for induction of anesthesia Two agents
Thiopental sodium (Pentothal) Methohexital sodium (Brevital)
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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
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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
Adverse effects Can cause profound respiratory depression Can cause hypotension Risk of bacterial infection
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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
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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
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Etomidate
Potent hypnotic agent Used for induction Repeated administration can cause
hypotension, oliguria, electrolyte disturbances, and high incidence of postoperative nausea and vomiting
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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
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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