indication

For use as the sole anesthetic agent for brief (15 minute) procedures, for induction of anesthesia prior to administration of other anesthetic agents, to supplement regional anesthesia, to provide hypnosis during balanced anesthesia with other agents for analgesia or muscle relaxation, for the control of convulsive states during or following inhalation anesthesia or local anesthesia, in neurosurgical patients with increased intracranial pressure, and for narcoanalysis and narcosynthesis in psychiatric disorders.

pharmacology

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

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.

toxicity

Overdosage may occur from too rapid or repeated injections. Too rapid injection may be followed by an alarming fall in blood pressure even to shock levels. Apnea, occasional laryngospasm, coughing and other respiratory difficulties with excessive or too rapid injections may occur. Lethal blood levels may be as low as 1 mg/100 mL for short-acting barbiturates; less if other depressant drugs or alcohol are also present.

biotransformation

Primarily hepatic. Biotransformation products of thiopental are pharmacologically inactive and mostly excreted in the urine.

absorption

Rapidly absorbed.

half life

3-8 hours

drug interactions

Acenocoumarol: Thiopental may increase the metabolism of the Vitamin K antagonist, Acenocoumarol. Acenocoumarol dose adjustment may be required.

Amlodipine: The CYP3A4 inducer, Thiopental, may increase the metabolism and clearance of Amlodipine, a CYP3A4 substrate. Monitor for changes in the therapeutic/adverse effects of Amlodipine if Thiopental is initiated, discontinued or dose changed.

Chloramphenicol: Chloramphenicol may increase the serum concentration of Thiopental by decreasing Thiopental metabolism. Thiopental may decrease the serum concentration of Chloramphenicol by increasing Chloramphenicol metabolism. Monitor for changes in therapeutic effects of both agents if concomitant therapy is initiated, discontinued or doses are adjusted.

Cyclosporine: Thiopental may increase the metabolism and clearance of Cyclosporine. Monitor for changes in the therapeutic/adverse effects of Cyclosporine if Thiopental is initiated, discontinued or dose changed.

Desogestrel: Thiopental may decrease the effect of Desogestrel. Contraceptive failure may occur. Alternative nonhomomonal contraception should be used during concomitant therapy.

Diltiazem: The CYP3A4 inducer, Thiopental, may increase the metabolism and clearance of Diltiazem, a CYP3A4 substrate. Monitor for changes in the therapeutic/adverse effects of Diltiazem if Thiopental is initiated, discontinued or dose changed.

Disopyramide: Thiopental may increase the metabolism and clearance of Disopyramide. Monitor for changes in therapeutic/adverse effects of Disopyramide if Thiopental is inititaed, discontinued or dose changed.

Doxycycline: Thiopental may decrease the serum levels of Doxycycline. A reduction in antimicrobial effects may occur. An alternative antibiotic may be considered.

Drospirenone: Thiopental may decrease the effect of Drospirenone. Contraceptive failure may occur. Alternative nonhomomonal contraception should be used during concomitant therapy.

Ethinyl Estradiol: Thiopental may decrease the effect of Ethinyl estradiol. Contraceptive failure may occur. Alternative nonhomomonal contraception should be used during concomitant therapy.

Ethynodiol Diacetate: Thiopental may decrease the effect of Ethynodiol diacetate. Contraceptive failure may occur. Alternative nonhomomonal contraception should be used during concomitant therapy.

Etonogestrel: Thiopental may decrease the effect of Etonogestrel. Contraceptive failure may occur. Alternative nonhomomonal contraception should be used during concomitant therapy.

Felodipine: The CYP3A4 inducer, Thiopental, may increase the metabolism and clearance of Felodipine, a CYP3A4 substrate. Monitor for changes in the therapeutic/adverse effects of Felodipine if Thiopental is initiated, discontinued or dose changed.

Isradipine: The CYP3A4 inducer, Thiopental, may increase the metabolism and clearance of Isradipine, a CYP3A4 substrate. Monitor for changes in the therapeutic/adverse effects of Isradipine if Thiopental is initiated, discontinued or dose changed.

Lamotrigine: Thiopental may increase the metabolism and clearance of Lamotrigine. Monitor for decreased therapeutic effect of Lamotrigine if Thiopental is initiated.

Levonorgestrel: Thiopental may decrease the effect of Levonorgestrel. Contraceptive failure may occur. Alternative nonhomomonal contraception should be used during concomitant therapy.

Medroxyprogesterone: Thiopental may decrease the effect of Medroxyprogesterone. Contraceptive failure may occur. Alternative nonhomomonal contraception should be used during concomitant therapy.

Mestranol: Thiopental may decrease the effect of Mestranol. Contraceptive failure may occur. Alternative nonhomomonal contraception should be used during concomitant therapy.

Methadone: Thiopental may decrease the effect of Methadone by increasing Methadone metabolism. Methadone withdrawal may occur.

Nicardipine: The CYP3A4 inducer, Thiopental, may increase the metabolism and clearance of Nicardipine, a CYP3A4 substrate. Monitor for changes in the therapeutic/adverse effects of Nicardipine if Thiopental is initiated, discontinued or dose changed.

Nifedipine: The CYP3A4 inducer, Thiopental, may increase the metabolism and clearance of Nifedipine, a CYP3A4 substrate. Monitor for changes in the therapeutic/adverse effects of Nifedipine if Thiopental is initiated, discontinued or dose changed.

Nimodipine: The CYP3A4 inducer, Thiopental, may increase the metabolism and clearance of Nimodipine, a CYP3A4 substrate. Monitor for changes in the therapeutic/adverse effects of Nimodipine if Thiopental is initiated, discontinued or dose changed.

Nisoldipine: The CYP3A4 inducer, Thiopental, may increase the metabolism and clearance of Nisoldipine, a CYP3A4 substrate. Monitor for changes in the therapeutic/adverse effects of Nisoldipine if Thiopental is initiated, discontinued or dose changed.

Nitrendipine: The CYP3A4 inducer, Thiopental, may increase the metabolism and clearance of Nitrendipine, a CYP3A4 substrate. Monitor for changes in the therapeutic/adverse effects of Nitrendipine if Thiopental is initiated, discontinued or dose changed.

Norethindrone: Thiopental may decrease the effect of Norethindrone. Contraceptive failure may occur. Alternative nonhomomonal contraception should be used during concomitant therapy.

Norgestimate: Thiopental may decrease the effect of Norgestimate. Contraceptive failure may occur. Alternative nonhomomonal contraception should be used during concomitant therapy.

Propafenone: Thiopental may increase the metabolism and clearance of Propafenone. Monitor for decreased therapeutic effect of Propafenone if Thiopental is initiated.

Quinidine: Thiopental may increase the metabolism and clearance of Quinidine. Monitor for decreased therapeutic effect of Quinidine if Thiopental is initiated.

Trimipramine: The barbiturate, Thiopental, may increase the metabolism and clearance of Trimipramine. Monitor for changes in the therapeutics and adverse effects of Trimipramine if Thiopental is initiated, discontinued or dose changed. Dose adjustments of Trimipramine may be required.

Triprolidine: The CNS depressants, Triprolidine and Thiopental, may increase adverse/toxic effects due to additivity. Monitor for increased CNS depressant effects during concomitant therapy.

Verapamil: Thiopental, a CYP3A4 inducer, may increase the serum concentration of Verapamil, a CYP3A4 substrate. Monitor for changes in the therapeutic/adverse effects of Verapamil if Thiopental is initiated, discontinued or dose changed.

Warfarin: Thiopental may decrease the serum concentration of warfarin by increasing its metabolism. Monitor for changes in the therapeutic and adverse effects of warfarin if thiopental is initiated, discontinued or dose changed.