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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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