indication

Methohexital is indicated for use as an intravenous anaesthetic. It has also been commonly used to induce deep sedation.

pharmacology

Methohexital, 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. Little analgesia is conferred by barbiturates; their use in the presence of pain may result in excitation.

mechanism of action

Methohexital 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

The onset of toxicity following an overdose of intravenously administered methohexital will be within seconds of the infusion. If methohexital is administered rectally or is ingested, the onset of toxicity may be delayed. The manifestations of an ultrashort-acting barbiturate in overdose include central nervous system depression, respiratory depression, hypotension, loss of peripheral vascular resistance, and muscular hyperactivity ranging from twitching to convulsive-like movements. Other findings may include convulsions and allergic reactions. Following massive exposure to any barbiturate, pulmonary edema, circulatory collapse with loss of peripheral vascular tone, and cardiac arrest may occur.

biotransformation

Metabolism occurs in the liver through demethylation and oxidation. Side-chain oxidation is the most important biotransformation involved in termination of biologic activity.

absorption

The absolute bioavailability following rectal administration of methohexital is 17%.

half life

5.6 ± 2.7 minutes

route of elimination

Excretion occurs via the kidneys through glomerular filtration.

drug interactions

Aminophylline: The barbiturate, methohexital, decreases the effect of aminophylline.

Betamethasone: The barbiturate, methohexital, may decrease the effect of the corticosteroid, betamethasone.

Clomifene: The enzyme inducer, methohexital, decreases the effect of the hormone agent, clomifene.

Conjugated Estrogens: The enzyme inducer, methohexital, decreases the effect of the hormone agent, conjugated estrogens.

Cyclosporine: The barbiturate, methohexital, increases the effect of cyclosporine.

Dexamethasone: The barbiturate, methohexital, may decrease the effect of the corticosteroid, dexamethasone.

Diethylstilbestrol: The enzyme inducer, methohexital, decreases the effect of the hormone agent, diethylstilbestrol.

Doxycycline: The anticonvulsant, methohexital, decreases the effect of doxycycline.

Estradiol: The enzyme inducer, methohexital, decreases the effect of the hormone agent, estradiol.

Ethinyl Estradiol: This product may cause a slight decrease of contraceptive effect

Felodipine: The barbiturate, methohexital, decreases the effect of felodipine.

Fludrocortisone: The barbiturate, methohexital, may decrease the effect of the corticosteroid, fludrocortisone.

Folic Acid: Folic acid decreases the effect of anticonvulsant, methohexital.

Gefitinib: The CYP3A4 inducer, methohexital, may decrease the serum concentration and therapeutic effects of gefitinib.

Griseofulvin: The barbiturate, methohexital, decreases the effect of griseofulvin.

Hydrocortisone: The barbiturate, methohexital, may decrease the effect of the corticosteroid, hydrocortisone.

Levonorgestrel: Phenobarbital decreases the effect of levonorgestrel

Medroxyprogesterone: The enzyme inducer, methohexital, decreases the effect of the hormone agent, medroxyprogesterone.

Megestrol: The enzyme inducer, methohexital, decreases the effect of the hormone agent, megestrol.

Methadone: The barbiturate, methohexital, decreases the effect of methadone.

Metronidazole: The barbiturate, methohexital, decreases the effect of metronidazole.

Nifedipine: The barbiturate, methohexital, decreases the effect of the calcium channel blocker, nifedipine.

Norethindrone: This product may cause a slight decrease of contraceptive effect

Oxtriphylline: The barbiturate, methohexital, decreases the effect of oxtriphylline.

Prednisolone: The barbiturate, methohexital, may decrease the effect of the corticosteroid, prednisolone.

Prednisone: The barbiturate, methohexital, may decrease the effect of the corticosteroid, prednisone.

Quinidine: The anticonvulsant, methohexital, decreases the effect of quinidine.

Theophylline: The barbiturate, methohexital, decreases the effect of theophylline.

Triamcinolone: The barbiturate, methohexital, may decrease the effect of the corticosteroid, triamcinolone.

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

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

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

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