Pharmacological properties : תכונות פרמקולוגיות

Pharmacodynamic Properties

5.2   Pharmacodynamics
Lithium is inactive in most screening psychopharmacological tests, but it produces marked potentiation of amphetamine hyperactivity in animals. It does not appear to protect against the action of stimulant and convulsive drugs and produces only slight potentiation of CNS depressants.
Lithium can replace sodium in extracellular fluid and during the process of depolarization it has an extremely rapid intracellular influx. However, it is not effectively removed by the sodium pump, thereby preventing the cellular re-entry of potassium. As a result, it interferes with electrolyte distribution across the neuronal membrane, leading to a fall in membrane potential and changes in conduction and neuronal excitability. In humans, lithium alters the excitability of the CNS as measured by cortical-evoked potentials.
Balance studies indicate that lithium may produce a transitory diuresis with increase in sodium and potassium excretion. A period of equilibrium or slight retention may follow, but persistent polyuria may occur in some patients.
There is evidence that therapeutic doses of lithium decrease the 24-hour exchangeable sodium. Longitudinal metabolic studies have demonstrated cumulative lithium retention in some patients without undue rise in plasma lithium values, indicating a possible intracellular retention of lithium. There is some evidence that lithium may affect the metabolism of potassium, magnesium and calcium.
There is evidence to indicate that lithium might produce a shift in norepinephrine metabolism from o-methylation to intraneuronal deamination, as evidenced by a decrease in normetanephrine and an increase in deaminated catechols observed in animal studies. This would suggest that lithium may decrease levels of norepinephrine available at the central adrenergic receptors. It would appear, however, that this action is not specific of lithium.
Lithium may also alter the metabolism of other monoamines such as serotonin. EKG changes with lithium have been reported in both animals and man.

Pharmacokinetic Properties