Definition
A barbituric acid derivative that acts as a nonselective central nervous system depressant. It potentiates GAMMA-AMINOBUTYRIC ACID action on GABA-A RECEPTORS, and modulates chloride currents through receptor channels. It also inhibits glutamate induced depolarizations.
Description
Phenobarbital is only found in individuals that have used or taken this drug. It is a barbituric acid derivative that acts as a nonselective central nervous system depressant. It promotes binding to inhibitory gamma-aminobutyric acid subtype receptors, and modulates chloride currents through receptor channels. It also inhibits glutamate induced depolarizations. [PubChem] Phenobarbital acts on GABAA receptors, increasing synaptic inhibition. This has the effect of elevating seizure threshold and reducing the spread of seizure activity from a seizure focus. Phenobarbital may also inhibit calcium channels, resulting in a decrease in excitatory transmitter release. The sedative-hypnotic effects of phenobarbital are likely the result of its effect on the polysynaptic midbrain reticular formation, which controls CNS arousal.
Top Gene Interactions
Related Pathways
General Information
- Metabolism: Hepatic (mostly via CYP2C19). Half Life: 53 to 118 hours (mean 79 hours)
- Uses/Sources: For the treatment of all types of seizures except absence seizures.
- Health Effects: They cause slurred speech, disorientation and "drunken" behavior. They are physically and psychologically addictive. May cause a potentially dangerous rash that may develop into Stevens Johnson syndrome, an extremely rare but potentially fatal skin disease.
- Symptoms: CNS and respiratory depression which may progress to Cheyne-Stokes respiration, areflexia, constriction of the pupils to a slight degree (though in severe poisoning they may wshow paralytic dilation), oliguria, tachycardia, hypotension, lowered body temperature, and coma. Typical shock syndrome (apnea, circulatory collapse, respiratory arrest, and death) may occur.
- Treatment: Treatment of overdosage is mainly supportive and consists of maintaining an adequate airway with assisted respiration and oxygen administration as necessary, as well as monitoring of vital signs and fluid balance. If the patient is conscious and has not lost the gag reflex, emesis may be induced with ipecac. Care should be taken to prevent pulmonary aspiration of vomitus. After completion of vomiting, 30 grams activated charcoal in a glass of water may be administered. If emesis is contraindicated, gastric lavage may be performed with a cuffed endotracheal tube in place with the patient in the face down position. Activated charcoal may be left in the emptied stomach and a saline cathartic administered. Fluid therapy and other standard treatment for shock should be performed if needed. If renal function is normal, forced diuresis may aid in the elimination of the barbiturate. Alkalinization of the urine increases renal excretion of some barbiturates, especially phenobarbital, also aprobarbital, and mephobarbital (which is metabolized to phenobarbital). Although not recommended as a routine procedure, hemodialysis may be used in severe barbiturate intoxications or if the patient is anuric or in shock. Patient should be rolled from side to side every 30 minutes, and antibiotics should be given if pneumonia is suspected. Appropriate nursing care to prevent hypostatic pneumonia, decubiti, aspiration and other complications of patients with altered states of consciousness should also be performed. (L1712)
- Route of Exposure: Absorbed in varying degrees following oral, rectal or parenteral administration. The salts are more rapidly absorbed than are the acids. The rate of absorption is increased if the sodium salt is ingested as a dilute solution or taken on an empty stomach.
Mechanism of Action
Target Name | Mechanism of Action | References |
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Potassium voltage-gated channel subfamily H member 2 Sodium channel protein type 3 subunit alpha Neuronal acetylcholine receptor subunit alpha-4 Neuronal acetylcholine receptor subunit alpha-7 Glutamate receptor 2 Glutamate receptor ionotropic, kainate 2 Nuclear receptor subfamily 1 group I member 2 NMDA receptor |
11264449 15324906 14977870 16248797 20051697 18262683 15039302 7862741 3016269 10487207 |
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Gamma-aminobutyric acid receptor subunit alpha-1 | Phenobarbital acts on GABAA receptors, increasing synaptic inhibition. This has the effect of elevating seizure threshold and reducing the spread of seizure activity from a seizure focus. Phenobarbital may also inhibit calcium channels, resulting in a decrease in excitatory transmitter release. The sedative-hypnotic effects of phenobarbital are likely the result of its effect on the polysynaptic midbrain reticular formation, which controls CNS arousal. |
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