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First Generation Antipsychotics: Pharmacokinetics, Pharmacodynamics, Therapeutic Effects and Side Effects: A Review

Getinet Ayano

The pharmacokinetics, pharmacodynamics, therapeutic effects and side effects of common first generation antipsychotics is reviewed, and the possible relevance treatment for the side effects is discussed. The first-generation antipsychotics (FGAs) also known as, typical antipsychotics, dopamine antagonists, neuroleptics, traditional, old generation and classic antipsychotics represent the first group of effective agents for schizophrenia and other psychotic illnesses. They include all of the antipsychotics in the following groups: phenothiazines, butyrophenones, thioxanthenes, dibenzoxazepines, dihydroindoles, and diphenylbutylpiperidines. Primary mechanism of action of firstgeneration antipsychotics is postsynaptic blockade of the dopamine receptor (D-2 receptor). As a result, they reduce dopaminergic neurotransmission in dopamine pathways. All antipsychotics are considered equally effective. Rationale for determining which medication to use is based on side effect profile. First-generation antipsychotics are well absorbed when they are administered orally or parentally. As with most drugs, oral administration leads to less predictable absorption than parenteral administration. Plasma concentrations of the drugs usually reach peak levels 1 to 4 hours after ingestion and 30 to 60 minutes after intramuscular (IM) administration. They are metabolized in the liver by CYP450 enzymes. Three of the CYP450 enzymes such as CYP1A2, CYP2D6 and CYP3A4 are involved in metabolism of first generation antipsychotics. The most serious side effects of dopamine receptor antagonists are neurological and are largely confined to the extrapyramidal motor system. Acute dystopia, Akathesia, Drug- Induced Parkinsonism, neuroeleptic malignant syndromes and tardive dyakinesia are common extrapyramidal side effects associated with use first generation antipsychotics. Postural hypotension, tachycardia, sedations, blurred vision, dry mouth, constipation, urinary retention, and memory dysfunction are common non neurologic side effects of FGAs.