Phenobarbitone Idaman Mechanism of Action

Pharmacology: Pharmacodynamics: Phenobarbitone is a long-acting barbiturate. It is widely used in the treatment of epilepsy due to its depressant effect on motor cortex. It also has sedative effect and some protective action against all varieties of human partial and generalised epilepsy. Phenobarbitone proven to have inconsistent effect on suppressing experimental epileptic foci and epileptic after discharges however, it inhibits synaptic transmission at spinal cord. The drug acts by prolonging opening of CI^- ion channels in postsynaptic neuronal membranes which leads to hyperpolarisation and impairs nerve impulse propagation. Phenobarbitone also decreases inter-neuronal Na⁺ concentrations and inhibits Ca⁺ influx into depolarised synaptosomes. The drug increases serotonin levels and inhibits noradrenaline (norepinephrine) reuptake into synaptosomes.
Pharmacodynamics: Absorption: Phenobarbitone is readily absorbed from gastrointestinal tract. It is relatively lipid-insoluble. Peak concentrations are achieved in about 2 hours after oral dose administration.
Distribution: Phenobarbitone is about 45-60% bound to plasma proteins. It crosses the placenta and is present in breast milk. Phenobarbitone is distributed to all tissues and fluids with high concentration in the brain, liver and kidneys.
Metabolism: Plasma half-life of phenobarbitone is about 75 to 120 hours in adults and about 21-75 hours in children. It is greatly prolonged in neonates. Phenobarbitone kinetics show considerable interindividual variation. It is only partly metabolised in the liver.
Elimination: Approximately 25% of the phenobarbitone dose is excreted unchanged in the urine at normal urinary pH.