indication

For the short-term treatment of insomnia.

pharmacology

Pentobarbital, a barbiturate, is used for the treatment of short term insomnia. It belongs to a group of medicines called central nervous system (CNS) depressants that induce drowsiness and relieve tension or nervousness. Little analgesia is conferred by barbiturates; their use in the presence of pain may result in excitation.

mechanism of action

Pentobarbital binds at a distinct binding site associated with a Cl- ionopore at the GABAA 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. All of these effects are associated with marked decreases in GABA-sensitive neuronal calcium conductance (gCa). The net result of barbiturate action is acute potentiation of inhibitory GABAergic tone. Barbiturates also act through potent (if less well characterized) and direct inhibition of excitatory AMPA-type glutamate receptors, resulting in a profound suppression of glutamatergic neurotransmission.

toxicity

Symptoms of an overdose typically include sluggishness, incoordination, difficulty in thinking, slowness of speech, faulty judgment, drowsiness or coma, shallow breathing, staggering, and in severe cases coma and death.

biotransformation

by hepatic microsomal enzyme system

absorption

Barbiturates are absorbed in varying degrees following oral, rectal, or parenteral administration.

half life

5 to 50 hours (dose dependent)

route of elimination

Barbiturates are metabolized primarily by the hepatic microsomal enzyme system, and the metabolic products are excreted in the urine, and less commonly, in the feces. Approximately 25 to 50 percent of a dose of aprobarbital or phenobarbital is eliminated unchanged in the urine, whereas the amount of other barbiturates excreted unchanged in the urine is negligible.

drug interactions

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Levonorgestrel: Phenobarbital decreases the effect of levonorgestrel

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

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

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

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

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

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

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

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

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

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

Telithromycin: Pentobarbital may decrease the plasma concentration of Telithromycin. Consider alternate therapy.

Temsirolimus: Pentobarbital may increase the metabolism of Temsirolimus decreasing its efficacy. Concomitant therapy should be avoided.

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

Tramadol: Pentobarbital may decrease the effect of Tramadol by increasing Tramadol metabolism and clearance.

Trazodone: The CYP3A4 inducer, Pentobarbital, may decrease Trazodone efficacy by increasing Trazodone metabolism and clearance. Monitor for changes in Trazodone efficacy/toxicity if Pentobarbital is initiated, discontinued or dose changed.

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

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

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

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

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