6. 0
Phenobarbital 1s
Drugsused in the prophylaxisof epileptic seizures
• Barbiturate drug, trade name
O H
Luminal O C 3
H
H N
N C CH • MainlyC Anticonvulsant
as C H5
2
2 5 O C O C
O C • Hypnotic effect, Sedative effect,
C
N N
N C • Bioavailability after proper
H H O
H administration = 95%
O
• Metabolism= Hepatic
Phenobarbital (Cytochrome P450) E
P henytoin thosuximide
• Half-life= 53-118 hours
C 2
H
• Excretion= Renal and Fecal
HC
C 2
H NH2 H2C NH2
HC NH2
C 2
H
C C 2
H
7. Clinical Use
• Phenobarbital is useful in the treatment of
partial seizures and generalized tonic-clonic
seizures, although the drug is often tried for
virtually every seizure type, especially when
attacks are difficult to control
• Depresses neurons activities via Reticular
Formation, Induces sleep
(Sedative, Hypnotics, and Anesthetics)
9. GABA-mediated chloride ion channel
from Zorumski CF, Isenberg KE: Insights into the structure and function of GABA receptors: Ion
channels and psychiatry. Am J Psychiatry 1991;148:162.)
10. Pharmacokinetics
• The rates of oral absorption of sedative-
hypnotics differ depending on a number of
factors, including lipophilicity.
• Most of the barbiturates and other older
sedative-hypnotics, as well as the newer
hypnotics
(eszopiclone, zaleplon, zolpidem), are
absorbed rapidly into the blood following oral
administration.
11. Pharmacodynamics
• Benzodiazepines and phenobarbital augment
the activation of the GABAA receptor by
physiologically released amounts of GABA.
• Elongates the GABA-mediated Chloride Ion
Channel Opening.
• Elongates GABA and Glycine Inhibitory Effect
• Chloride influx is increased, counteracting
depolarization.
• Depresses the CNS via Reticular Formation.
• Induces sleep (Sedative, Hypnotics, and
Anesthetics)
Notas do Editor
A model of the GABAA receptor-chloride ion channel macromolecular complex (others could be proposed). A heterooligomeric glycoprotein, the complex consists of five or more membrane-spanning subunits. Multiple forms of , , and subunits are arranged in different pentameric combinations so that GABAA receptors exhibit molecular heterogeneity. GABA appears to interact with or subunits triggering chloride channel opening with resulting membrane hyperpolarization. Binding of benzodiazepines to subunits or to an area of the unit influenced by the unit facilitates the process of channel opening but does not directly initiate chloride current. (Modified and reproduced, with permission,