Drugs treating psychotic disorders and dementia

• Thought, like mood, is controlled by combinations of neurotransmitters that stimulate neuroreceptors in the brain. The primary neurotransmitter related to thought processing is believed to be dopamine. • Another important neurotransmitter is acetylcholine. Many areas of the brain secrete acetylcholine; reduction in the amount of this neurotransmitter causes cognitive changes. Acetylcholine has a number of functions including arousal, coordination of movement, memory acquisition, and memory retention. Norepinephrine and serotonin are other neurotransmitters that are believed to be important to normal thought, but their exact mechanisms are not known yet. • Schizophrenia, a psychotic disorder, has components termed positive and negative symptoms. The term "positive symptom" does not mean that the changes are benefi - cial to the patient. The positive symptoms of hallucinations and delusions add a layer of something new to the person. They are in excess of or are a distortion of normal brain function. The "negative symptoms" take away from the person's personality and represent a loss or a diminishing of normal brain function. Negative symptoms include fl at or blunted emotions, lack of pleasure or interest in things (anhedonia), and limited speech. • Haloperidol (Haldol) is the prototype typical antipsychotic. It is used to treat psychotic disorders, such as schizophrenia, and relieves primarily positive symptoms. The full therapeutic effect from haloperidol can require several days to develop. Haloperidol creates its effects by blocking dopamine (specifi cally, D2), alpha, serotonin, and histamine receptors. It has minimal blocking effects on cholinergic receptors. • Haloperidol's blockade of dopaminergic receptors produces decreased symptoms of movement disorders, relief of hallucinations and delusions, relief of psychosis, worsened negative symptoms, a release of prolactin, and a quieting of the chemoreceptive trigger zone in the brain. Its blockade of alpha, serotonin, histamine, and cholinergic receptors produces many of its adverse effects. • The most common reason patients stop taking antipsychotic medications like haloperidol is the occurrence of adverse effects. The higher the dose of haloperidol, the more likely the patient will experience adverse effects. Stopping and starting therapy also increases the likelihood of developing extrapyramidal symptoms (EPS). Encourage the patient to stay with therapy, because some of the adverse effects are transient and can be managed. • Chlorpromazine (Thorazine), thioridazine (Mellaril), and mesoridazine (Serentil) are all considered low-potency typical antipsychotics, compared with haloperidol, which is a high-potency antipsychotic. A higher dosage of these drugs is necessary to achieve the same antipsychotic affect as those achieved with haloperidol. Both types of typical antipsychotics have the same effectiveness, although they have different adverse effects. High-potency typical antipsychotics, such as haloperidol, have a very high likelihood of causing EPS (e.g., dystonias, akathisia, and Parkinsonlike adverse effects). Low-potency typical antipsychotics are more likely to produce sedation and anticholinergic adverse effects but are unlikely to produce EPS. • Atypical antipsychotics differ from the typical antipsychotics in that they target specifi c dopamine receptors instead of all of them and that they treat both the negative and positive symptoms of psychotic disorders. • In general, atypical antipsychotics such as olanzapine are well tolerated and produce few adverse effects, although some patients experience sedation and dizziness. Elevated blood glucose levels can also be problematic, especially for patients with diabetes. • Drugs that augment levels of acetylcholine, by preventing its breakdown by acetylcholinesterase, compensate for losses of cholinergic function in the brain and are used to treat Alzheimer-type dementia. Rivastigmine (Exelon) is the prototype acetylcholinesterase inhibitor (AChEI). • Rivastigmine produces modest improvement in some measures of cognitive functioning and in other areas of functioning in the patient with mild to moderate Alzheimer disease, apparently slowing the progression of the disease. The most common adverse effects are gastrointestinal. • Memantine is also used to treat patients with Alzheimer disease. It works in a unique way to prevent glutamine from overstimulating NMDA receptors. Its effect is also modest.