THIPEN INJECTION

Indications

• Induction of general anesthesia
• Short surgical procedures
• Diagnostic procedures requiring anesthesia

Dosage

Adults: For induction of anesthesia, the initial dose is typically 3 to

Mechanism of action

Thiopental binds at a distinct binding site associated with a Cl- ionopore at the GABAA receptor, increasing the duration for which the Cl- ionopore is open. This prolongs the post-synaptic inhibitory effect of GABA in the thalamus, enhancing the inhibitory neurotransmission in the CNS. The exact mechanisms by which thiopentone and other barbiturates exert their effects are not completely understood, but it involves an imbalance in central inhibitory and facilitatory mechanisms influencing the cerebral cortex and reticular formation.

Pharmacodynamics

Thiopental is an ultrashort-acting CNS depressant that induces hypnosis and anesthesia rapidly. Following intravenous administration, hypnosis occurs within 30 to 40 seconds. The drug's effects are primarily due to its enhancement of GABA activity, leading to decreased excitability of presynaptic and postsynaptic membranes. Recovery after administration is typically quick, but repeated dosing may lead to prolonged anesthesia due to accumulation in fatty tissues, where it can concentrate at levels significantly higher than in plasma.

Pharmacokinetics

Thiopental is administered intravenously, leading to rapid distribution throughout the body, particularly in highly perfused organs such as the brain. The onset of action is swift, typically within 30 to 40 seconds. The drug is metabolized in the liver, with the elimination half-life extending after repeated doses due to accumulation in body fat. Recovery from anesthesia can be influenced by the redistribution of thiopental from fat stores back into circulation, prolonging its effects. Renal excretion is the primary route for elimination of its metabolites.

Contra-indications

• Hypersensitivity to thiopental or other barbiturates
• Porphyria
• Severe respiratory insufficiency
• Severe liver dysfunction
• Acute intermittent porphyria

Adverse effects

• Respiratory depression
• Hypotension
• Cardiovascular collapse
• Allergic reactions
• Somnolence
• Retrograde amnesia
• Injection site reactions

Interactions

• CNS depressants (e.g., alcohol, benzodiazepines) may enhance the depressant effects of thiopental
• Enzyme inducers (e.g., rifampicin, phenytoin) may reduce the efficacy of thiopental
• Opioids may enhance the sedative effects of thiopental

Precautions

• Use with caution in patients with respiratory disease
• Monitor hemodynamic status in patients with cardiovascular disease
• Consider dose adjustment in elderly patients or those with compromised liver function
• Ensure availability of resuscitation equipment

Pregnancy

Thiopental should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. It crosses the placenta.

Breast-feeding

Caution is advised as thiopental is excreted in breast milk. Monitor the infant for sedation.

Storage

Store in a cool, dry place, protected from light. Keep out of reach of children.

Formulations

• Injection solution (e.g., thiopental sodium for injection)

Mechanism of action

Thiopental binds at a distinct binding site associated with a Cl^- ionopore at the GABA_A receptor, increasing the duration of time for which the Cl^- ionopore is open. The post-synaptic inhibitory effect of GABA in the thalamus is, therefore, prolonged. The exact mechanism(s) by which barbiturates exert their effect on the CNS, has not been fully elucidated. However, it is believed that such effects are related, at least partially, to the drugs' ability to enhance the activity of gamma-aminobutyric acid (GABA), the principal inhibitory neurotransmitter in the CNS, by altering inhibitory synaptic transmissions that are mediated by GABAA receptors. /Barbiturates General Statement/ Although the drugs act throughout the CNS, a site of particular sensitivity is the polysynaptic midbrain reticular formation which is concerned with the arousal mechanism. Barbiturates induce an imbalance in central inhibitory and facilitatory mechanisms influencing the cerebral cortex and the reticular formation. The significance of the effect of barbiturates on neurotransmitters is unclear. It appears that the drugs decrease the excitability of both presynaptic and postsynaptic membranes. It has not been determined which of the various actions of barbiturates at cellular and synaptic levels are responsible for their sedative and hypnotic effects. /Barbiturates General Statement/ Relatively low doses of the barbiturates depress the sensory cortex, decrease motor activity, and produce sedation and drowsiness. In some patients, however, drowsiness may be preceded by a period of transient elation, confusion, euphoria, or excitement, especially after subhypnotic doses of aprobarbital, pentobarbital, or secobarbital. /Barbiturates General Statement/ Larger doses distort judgment, cloud perception, suppress motor activity, and produce drowsiness and sleep. Still larger doses induce anesthesia. Barbiturate-induced sleep differs from physiologic sleep. Barbiturates reduce the rapid eye movement (REM) or dreaming stage of sleep. Stages III and IV sleep are also decreased. Although tolerance develops to the REM-suppressant effects during chronic administration, REM rebound occurs when the drugs are withdrawn, and the patient may experience markedly increased dreaming, nightmares, and/or insomnia. /Barbiturates General Statement/ For more Mechanism of Action (Complete) data for Thiopental (16 total), please visit the HSDB record page.

Pharmacodynamics

Thiopental, a barbiturate, is used for the induction of anesthesia prior to the use of other general anesthetic agents and for induction of anesthesia for short surgical, diagnostic, or therapeutic procedures associated with minimal painful stimuli. Thiopental is an ultrashort-acting depressant of the central nervous system which induces hypnosis and anesthesia, but not analgesia. It produces hypnosis within 30 to 40 seconds of intravenous injection. Recovery after a small dose is rapid, with some somnolence and retrograde amnesia. Repeated intravenous doses lead to prolonged anesthesia because fatty tissues act as a reservoir; they accumulate Pentothal in concentrations 6 to 12 times greater than the plasma concentration, and then release the drug slowly to cause prolonged anesthesia