Antipsychotic Medications

Antipsychotic medications are the main form of treatment for psychotic disorders, not just for the treatment of schizophrenia. They are also called neuroleptic drugs or neuroleptics. Antipsychotic medications first came into recognition in the 1950s when it was fortuatously first used as an anxiolytic for the treatment of delirium. It was noticed that it had a very calming effect and that psychotic symptoms also improved.

Chlorpromazine was the first antipsychotic drug that was developed

Mechanism of action

In order to understand how antipsychotic medications work, it is necessary to have a basic understanding of cellular physiology. Cells communicate with one another through the release of chemicals which then interact with other cells at points of attachment called receptors. When the chemical attached to the receptor, this sets off a chemical reaction in the second cell which results in various cellular changes and which ultimately leads to improvement in symptoms. Antipsychotic medications exert their antipsychotic through this same mechanism by acting on receptors of certain cells in the brain. These cells are situated in the part of the brain called the striatum.

There are 6 different subtypes of dopamine receptors and 15 subtypes of serotonin receptors. The one common factor between all the antipsychotic medications is interaction at the dopamine 2 (D2) receptor. They will also interact with other receptors to varying degrees. It is this interaction with various other receptors that lead to the adverse effects of the antipsychotic medications. Although the best evidence for response to treatment of schizophrenia lies with the D2 receptor, a lot still needs to be achieved, as we don't have a longterm cure for schizophrenia. There is a large amount of experimental research looking into the effects of drugs which act at other receptors besides D2 receptors.

There are also various methods whereby the drug molecules can interact at the receptor.

Most of the first generation drugs are what is termed dopamine blockers. That is, they attach to the D2 receptor and prevent the endogenous dopamine from attaching to the D2 receptor. They block the action of dopamine at the receptor - hence the name D2 blocker. In scientific terms, they are called antogonists - they antagonise the action of dopamine. Drugs which attach to receptors and promote the action of the receptor are called agonists.

Drugs can also be judged by the degree of potency of the action at the receptor. Amongst the first generation drugs, haloperidol is a high potency drug and chlopromazine is a low potency drug. Therefore the amount of chlopromazine required to have the same effect as haloperidol is about 10x more.

Drugs are also judged by the strength of the attachment to the receptor. If it is a strong bond and they can't be displaced by other molecules then it is a full agonist or full antagonist at that receptor. If their attachment to the receptor is less strong and it can be dispaced by another molecule then it is termed a partial agonist or antagonist. By having a partial attachment to a receptor, the effect at that receptor will be less than if it was bound all the time.

The newer second generation antipsychotics (also called atypical antipsychotics) are mostly partial dopamine antagonists. They also block serotonin receptors, and are hence called serotonin dopamine antogonists. A lot of the side effects of the antispychotic medications are also mediated by blockage of the D2 receptor. So by being partial D2 antagonists, the second generation drugs are able to exert less action at those receptors responsible for the side effects. But the strength of their action remains strong enough to have an antipsychotic effect in that part of the brain where the antipsychotic interaction occurs.

Indications

Antispychotic medications are used in a wide variety of conditions for psychotic symptoms and psychotic disorders, mood disorders with or without psychotic symptoms, severe aggression and disruptive behaviours, agitation, hypersexual disorders, attention deficit disorders, Alzheimers disease and some other dementias, and delirium. There is also indication for OCD (obsessive compulsive disorder), alcohol withdrawal delirium.

Types

There is a vast array of different antipsychotic medications and there is no value in listing all of them. The more commnly known ones are haloperidol, chlopromazine, fluphenazine, flupenthixol, zuclopenthixol, trifluoperazine, pimozide, perphenanazine, sulpiride,

The second generation antipsychotics are also termed dopamine-serotonin antagonists. The common ones include risperidone, olanzapine, quetipaine, aripiprazole, and zyprasidone. Zotepine, and iloperidone are also other second generation antipsychotics.

See this link for side effects of antipsychotic medications




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