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    dr. Isngadi, M.Kes., SpAn.

    Departement of PharmacologyDepartement of Anesthesiology & ReanimationDr Saiful Anwar Hospital, Brawijaya University

    Malang

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    Nonvolatile Anesthetic Agents

    Thiopental has become the gold standard

    Desirable Characteristics of an IV. Anesthetic:

    1. Drug compatibility and stability in solution

    2. Lack of pain on injection, venoirritation, or tissue

    damage from extravasation

    3. Low potential to release histamine or precipitate

    hypersensitivity reactions

    4. Rapid and smooth onset of action withoutexcitatory activity

    5. Rapid metabolism to pharmacologically inactive

    metabolites

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    6. A steep doseresponse relationship that enhances

    titratability and minimizes accumulation

    7. Lack of acute cardiovascular and respiratory

    depression

    8. Decreases in cerebral metabolism and intracranial

    pressure

    9. Rapid and smooth return of consciousness and

    cognitive skills

    10. Absence of postoperative nausea and vomiting,

    amnesia, psychomimetic reactions, dizziness,

    headache, or prolonged sedation (hangover)

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    Interaction with the inhibitory g-aminobutyric acid (GABA)

    neurotransmitter system.

    When the GABA-receptor is activated, transmembrane chloride

    conductance increases, resulting in hyperpolarization of the

    postsynaptic cell membrane and functional inhibition of the

    postsynaptic neuron.

    Sedative hipnotic drugs can interact with different components of

    the GABA-receptor complex

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    The CNS effects of ketamine appear to be primarily

    related to its antagonistic activity at the N-methyl-

    D-aspartate (NMDA) receptor . Unlike the other iv

    anesthetics, ketamine does not interact with GABA

    receptors

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    PHARMACOKINETIC VALUES FOR THE CURRENTLY AVAILABLE INTRAVENOUSSEDATIVE-HYPNOTIC DRUGS

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    Uses and Dosages of Commonly Used Barbiturates

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    Uses and Doses of Commonly Used Benzodiazepines.

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    Barbiturates depress the reticular activating systema

    complex polysynaptic network of neurons and regulatory

    centers.

    In clinical concentrations, barbiturates preferentially affect

    the function of nerve synapses rather than axons.

    They suppress transmission of excitatory neurotransmitters

    (eg, acetylcholine) and enhance transmission of inhibitory

    neurotransmitters (eg, -aminobutyric acid [GABA]). Specific mechanisms include interfering with transmitter

    release (presynaptic) and stereoselectively interacting with

    receptors (postsynaptic).

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    The most commonly used barbiturates are thiopental,

    methohexital, thiamylal

    All three barbiturates are available as sodium salts and must be

    dissolved in isotonic sodium chloride (0.9%) or water.

    When barbiturates are added to Ringers lactate or an acidic

    solution containing other water-soluble drugs, precipitation will

    occur and can occlude the iv catheter.

    Thiopental is metabolized in the liver to hydroxythiopental and

    the carboxylic acid derivativeThe usual induction dose of thiopental is 35 mgkg-1 in adults,

    56 mgkg-1 in children, and 68 mgkg-1 in infants.

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    Barbiturates produce a proportional decrease in CMRO2 and

    CBF, thereby lowering ICP. An isoelectric EEG can be maintained with a thiopental infusion

    rate of 46 mgkg-1h-1

    Thiopental is widely used to improve brain relaxation during

    neurosurgery and to improve cerebral perfusion pressure (CPP)

    after acute brain injury.

    Barbiturates cause dose-dependent respiratory depression.

    Laryngeal reflexes appear to be more active after induction with

    thiopental than with propofol.

    The cardiovascular effects of thiopental and methohexital

    include decreases in cardiac output, systemic arterial pressure,

    and peripheral vascular resistance

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    Drug Interactions

    Contrast media, sulfonamides, and other drugs thatoccupy the same protein-binding sites as thiopental

    will increase the amount of free drug available and

    potentiate the organ system effects of a given dose.

    Ethanol, opioids, antihistamines, and other central

    nervous system depressants potentiate the sedative

    effects of barbiturates. The common clinical

    impression that chronic alcohol abuse is associatedwith increased thiopental requirements lacks

    scientific proof.

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