The antipsychotic drugs

The antipsychotic drugs are divided into first- and second-generation agents. The first-generation drugs are further classified as “low potency” or “high potency.” This classification does not indicate clinical effectiveness of the drugs, but rather specifies affinity for the dopamine D2 receptor, which, in turn, may influence the adverse effect profile of the drug.

A. First-generation antipsychotics
The first-generation antipsychotic drugs (also called conventional, typical, or traditional antipsychotics) are competitive inhibitors at a variety of receptors, but their antipsychotic effects reflect competitive blocking of dopamine D2 receptors. First-generation antipsychotics are more likely to be associated with movement disorders known as extrapyramidal symptoms (EPS), particularly drugs that bind tightly to dopaminergic neuroreceptors, such as haloperidol.

B. Second-generation antipsychotic drugs
The second-generation antipsychotic drugs (also called “atypical” antipsychotics) have a lower incidence of EPS than the first- generation agents but are associated with a higher risk of metabolic side effects, such as diabetes, hypercholesterolemia, and weight gain. The second-generation drugs appear to owe their unique activity to blockade of both serotonin and dopamine and, perhaps, other receptors.

Therapeutic uses
1. Treatment of schizophrenia: The antipsychotics are considered the only efficacious pharmacological treatment for schizophrenia. The first-generation antipsychotics are most effective in treating positive symptoms of schizophrenia.
2. Prevention of nausea and vomiting: The older antipsychotics (most commonly, Prochlorperazine are useful in the treatment of drug-induced nausea.
3. Other uses: The antipsychotic drugs can be used as tranquilizers to manage agitated and disruptive behavior secondary to other disorders. Chlorpromazine is used to treat intractable hiccups.
Adverse effects
1. Extrapyramidal effects: The inhibitory effects of dopaminergic neurons are normally balanced by the excitatory actions of cholinergic neurons in the striatum. Blocking dopamine receptors alters this balance, causing a relative excess of cholinergic influence, which results in extrapyramidal motor effects.
2. Tardive dyskinesia: Long-term treatment with antipsychotics can cause this motor disorder. Patients display involuntary movements, including bilateral and facial jaw movements and “fly-catching” motions of the tongue.
3. Neuroleptic malignant syndrome: This potentially fatal reaction to antipsychotic drugs is characterized by muscle rigidity, fever, altered mental status and stupor, unstable blood pressure, and myoglobinemia.
4. Other effects: Drowsiness occurs due to CNS depression and antihistaminic effects, usually during the first few weeks of treatment.