Pharmacological properties : תכונות פרמקולוגיות

Pharmacodynamic Properties

5.1   Pharmacodynamic properties
Pharmacotherapeutic group: antipsychotics; phenothiazine with piperazine structure ATC code: N05AB02
Mechanism of action
Fluphenazine decanoate is a highly potent neuroleptic of the phenothiazine class. It primarily causes blockade of dopamine receptors and thereby reduces the effect of dopamine as a transmitter substance. Fluphenazine has a high affinity for D2- receptors. An increase in prolactin, a decrease in apomorphine and amphetamine hyperactivity andcatalepsy occur as a result.
The muscarinic acetylcholine, D1 and H1 receptors, and α1 adrenergic receptors are blocked to a lesser extent by fluphenazine.
The clinical profile of action is characterized by antipsychotic effects: reduction of delusion, hallucinations, schizophrenic self-disorders and disordered thinking, suppression of psychomotor agitation and affective tension.
The extrapyramidal motor adverse reactions are explained by the inhibition of dopaminergic transmission in the corpus striatum.

Pharmacokinetic Properties

5.2   Pharmacokinetic properties
Absorption
Following intramuscular injection of the oily solution, fluphenazine decanoate is broken down slowly to the non-esterified fluphenazine.
Distribution
Fluphenazine then reaches the bloodstream and from there enters the tissues and its site of action. This process occurs over a period of approximately 2-4 weeks after injection of fluphenazine decanoate and ensures therapeutically active levels for the interval between injections.
After administration of the depot preparation, a high blood level is reached within a few hours; this then rapidly falls again and on day 3 moves into a plateau phase with only a subsequent slight decrease.
Fluphenazine is distributed throughout the body because of its highly lipophilic nature. The volume of distribution is approximately 25 L/kg body weight. Fluphenazine is excreted in human milk and crosses the placenta and blood-brain barrier. Plasma protein binding is over 95%. The plasma half-life is approximately 20 hours.
Metabolism / elimination
Fluphenazine is almost completely broken down by the liver. In addition to glucuronidation of the hydroxyl group in the side chain, there is hydroxylation of the phenothiazine base via CYP2D6, sulfoxidation, dealkylation of the piperazine ring and subsequent cleavage of the ring. After glucuronidation, 80-95% of excretion is via bile.