THIOPENTAL SODIUM

Indications

• Induction of anesthesia prior to surgical procedures
• Short diagnostic and therapeutic procedures requiring anesthesia
• Procedures with minimal painful stimuli

Dosage

Adults: For induction of anesthesia, the usual dose is 3 to 5 mg/kg IV, adjusted according to the patient's response and clinical circumstances.

Mechanism of action

Thiopental binds at a distinct binding site associated with a Cl- ionopore at the GABAA receptor, thereby increasing the duration that the Cl- ionopore remains open. This enhances the inhibitory effects of gamma-aminobutyric acid (GABA), the main inhibitory neurotransmitter in the central nervous system. By altering inhibitory synaptic transmissions, thiopental produces its sedative and hypnotic effects, particularly affecting the midbrain reticular formation and the cerebral cortex.

Pharmacodynamics

As an ultrashort-acting CNS depressant, thiopental induces hypnosis and anesthesia rapidly upon intravenous administration. It is especially effective for short procedures involving minimal painful stimuli. While the drug affects various neurotransmitters, its principal action is through enhancing GABA activity, leading to decreased excitability of neuronal membranes. Fatty tissues accumulate thiopental, which can result in prolonged anesthesia following repeated doses.

Pharmacokinetics

Thiopental is rapidly distributed throughout the body, with a quick onset of action following intravenous injection. The drug is highly lipophilic, allowing for rapid accumulation in fatty tissues, where it may remain for extended periods. Metabolism occurs primarily in the liver, and the pharmacokinetic profile is characterized by a short half-life that can be extended with repeated dosing due to accumulation. Clearance is dependent on liver function, and the drug's effects can be prolonged when it is released from fat stores.

Adverse effects

• Respiratory depression
• Hypotension
• Bradycardia
• Apnea
• Allergic reactions
• Somnolence
• Retrograde amnesia

Interactions

• Sulfonamides: Unknown (increases effects)

Precautions

• Use with caution in patients with respiratory depression
• Patients with a history of substance abuse
• Elderly patients may be more sensitive to effects

Pregnancy

Thiopental may cause fetal harm. Use in pregnancy only if the benefits outweigh the risks.

Breast-feeding

Use with caution; it is not known whether thiopental is excreted in human milk.

Storage

Store at room temperature, protect from light, and keep out of reach of children.

Formulations

• Injection solution

Indications

• Induction of general anesthesia
• Management of status epilepticus

Dosage

Children: Generally, up to 4 mg/kg body weight may be administered intravenously, adhering to maximum single dose limits as per clinical judgment and monitoring.

Adults: Initially 100–150 mg by slow intravenous injection, followed by 100–150 mg after 0.5–1 minute if required. Maximum single dose is 500 mg.

Mechanism of action

Thiopental sodium enhances the activity of gamma-aminobutyric acid (GABA) at the GABA_A receptor, leading to increased chloride ion conductance and hyperpolarization of neurons. This results in CNS depressant effects, leading to sedation and anesthesia. Additionally, it may inhibit excitatory neurotransmitter release, further contributing to its sedative properties.

Pharmacodynamics

Thiopental sodium produces rapid onset of anesthesia, typically within 30 to 60 seconds of intravenous administration. The duration of action is brief due to its redistribution from the central nervous system to peripheral tissues. The drug's effects can be prolonged in patients with compromised liver function or in those who are elderly, due to altered metabolism and clearance.

Pharmacokinetics

Thiopental sodium is administered intravenously and exhibits a rapid distribution phase with a half-life of approximately 4 to 12 hours. It is highly lipid-soluble, allowing for rapid central nervous system penetration. The drug is metabolized primarily in the liver via oxidative metabolism, and its metabolites are excreted in urine. Dosage adjustments may be necessary in patients with hepatic impairment or in the elderly.

Contra-indications

• Acute porphyrias
• Myotonic dystrophy

Adverse effects

• Arrhythmia
• Decreased myocardial contractility
• Hypotension
• Electrolyte imbalance
• Respiratory depression
• Skin eruptions
• Severe pain at injection site

Interactions

• Clonazepam may increase the risk of respiratory depression and hypotension
• Other central nervous system depressants may enhance sedative effects

Precautions

• Caution in patients with acute circulatory failure
• Caution in elderly patients
• Use with caution in patients with cardiovascular disease
• Monitor for signs of respiratory depression
• Avoid intra-arterial injection due to risk of tissue necrosis

Pregnancy

May depress neonatal respiration when used during delivery.

Breast-feeding

Breast-feeding can be resumed as soon as the mother has recovered sufficiently from anaesthesia.

Storage

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

Formulations

• Thiopental sodium 25 mg/mL solution for injection
• Thiopental sodium 500 mg/vial

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