Medications antipsychotics

Antipsychotic medications have truly revolutionized the treatment of psychotic disorders. Their effectiveness is so vastly superior to previous treatments that they have ushered in a new era in the treatment of severe mental illnesses. Chlorpromazine (Thorazine) was first used in 1952 as a postoperative sedative. It was subsequently used as a sedative for psychiatric patients, and it was soon discovered that it had antipsychotic properties. Soon other phenothiazines were developed. 

When these drugs were first used in clinical settings, the mechanism of action was unknown, although the medications were clearly quite successful in reducing psychotic symptoms. Later research determined that antipsychotic medications acted by producing a chemical blockade of dopamine D2 postsynaptic receptors and that their clinical potency correlated with their degree of dopamine blockade. This led to the dopamine hypothesis of schizophrenia (see chapter 9). 

chemically distinct dopamine blockers were then developed, such as thiothixene, haloperidol, loxapine, molindone, and pimozide. All of these antipsychotics are potent dopamine blockers and collectively were called neuroleptics because they inadvertently cause certain neurological side effects (discussed below). More recently, atypical antipsychotic medications have been developed (clozapine and risperidone), which are effective antipsychotics yet are weak dopamine blockers and cause minimal neurological side effects. This group is discussed separately below. 

The phenothiazines and similar antipsychotics can be divided into high-potency and low-potency groups (see figure 17-A). In addition, they can be ranked according to 

Generic Name Brand Name Dosage Range (mg/day) Equivalence (mg) 

Consequently, antipsychotic drugs all share a basic mechanism of action that involves dopamine receptor blockade. It is apparent, however, that they are not all equal in their ability to affect specific sub-types of dopamine receptors, and that their effectiveness and side effects are related to their affinity and preference for certain receptors. As indicated earlier, other neurotransmitters may also be involved in the pathogenesis of psychosis, and differences in specific antipsychotic medications may be related to their ability to directly or indirectly affect these other transmitters as well as block dopamine influence. Future studies will continue to clarify how current antipsychotics exert their beneficial effects and how new agents can be developed to be more selective in their effects on dopamine and other neurotransmitter pathways. 

---

This experiment describes a quantitative analysis for the active ingredients in a prescription antipsychotic medication. The separation makes use of a cyanopropyl derivatized column and a mobile phase of 70% v/v acetonitrile, 5% v/v methanol, and 25% v/v 0.1 M aqueous KH2PO4. A UV detector set to 215 nm is used to measure the eluent s absorbance. 

Antipsychotic medications are indicated in the treatment of acute and chronic psychotic disorders. These include schizophrenia, schizoaffective disorder, and manic states occurring as part of a bipolar disorder or schizoaffective disorder. The co-adminstration of antipsychotic medication with antidepressants has also been shown to increase the remission rate of severe depressive episodes that are accompanied by psychotic symptoms. Antipsychotic medications are frequently used in the management of agitation associated with delirium, dementia, and toxic effects of both prescribed medications (e.g. L-dopa used in Parkinson s disease) and illicit dtugs (e.g. cocaine, amphetamines, andPCP). They are also indicated in the management of tics that result from Gilles de la Tourette s syndrome, and widely used to control the motor and behavioural manifestations of Huntington s disease. 

Other sedative-hypnotic medications, such as barbiturates, may play a useful role in severe withdrawal from this group of drugs. For example, in a case series of GBL withdrawal, use of intravenous pentobarbital in the range of 1-2 mg/kg/hour lowered the total requirement for intravenous lorazepam (Sivilotti et al. 2001). Antipsychotic medications are often used to reduce psychotic agitation. However, because antipsychotic medications lower the seizure threshold and may contribute to loss of central control of temperature leading to hyperthermia or neuroleptic malignant syndrome (NMS), they are not indicated as first-line medications for GHB withdrawal delirium (Dyer and Roth 2001 McDaniel and Miotto 2001 Sharma et al. 2001). If anti-... 

George TP, Ziedonis DM, Feingold A, et al Nicotine transdermal patch and atypical antipsychotic medications for smoking cessation in schizophrenia. Am J Psychiatry 157 1835-1842, 2000... 

Changes in perceived physical and mental health status of a schizophrenia patient population following initiation of a conventional or an atypical antipsychotic medication. Poster presented at the American Psychiatric Association Annual Meeting, Toronto, June 1998. 

There is, however, a unique risk in the bipolar form that antidepressant treatment may trigger a switch into mania. This may occur either as the natural outcome of recovery from depression or as a pharmacological effect of the drug. Particular antidepressants (the selective serotonin reuptake inhibitors) seem less liable to induce the switch into mania than other antidepressants or electroconvulsive therapy. Treatment for mania consists initially of antipsychotic medication, for instance the widely used haloperidol, often combined with other less specific sedative medication such as the benzodiazepines (lorazepam intramuscularly or diazepam orally). The manic state will usually begin to subside within hours and this improvement develops further over the next 2 weeks. If the patient remains disturbed with manic symptoms, additional treatment with a mood stabilizer may help. 

Typical and atypical antipsychotic medications (D2-receptor antagonists)... 

Recommend appropriate antipsychotic medications based on patient-specific data. 

Describe the components of a monitoring plan to assess the effectiveness and safety of antipsychotic medications. 

The cornerstone of treatment is antipsychotic medications. Because most patients with schizophrenia relapse when not medicated, long-term treatment is usually necessary. 

Education of the patient and family regarding the benefits and risks of antipsychotic medications and the importance of adherence to their therapeutic regimens must be integrated into pharmacologic management. 

Since early detection and intervention in schizophrenia is important for maximizing outcomes, treatment with antipsychotic medications should begin as soon as psychotic symptoms are recognized. Antipsychotic medications are the cornerstone of therapy for people with schizophrenia, and most patients are on lifelong therapy since non-adherence and discontinuation of antipsychotics are associated with high relapse rates. If other symptoms are present such as depression and anxiety, these symptoms should also be aggressively treated. Additionally, psychosocial treatments should be used concomitantly to improve patient outcomes. 

Essentially all antipsychotic medications pass through the placenta. The use of these drugs requires critical attention to the timing of the exposure, the dose and duration of use, and fetal susceptibility. When possible, discontinuing antipsychotics for the first trimester is the safest option, as weeks 6 to 10 are the most vulnerable period for organ formation. 

Awad, A.G. et al. (1995). Patients subjective experiences on antipsychotic medications implications for outcome and quality oflife. Int. Clin. Psychopharmacol, 10(3), 123-32. 

Opolka, J. L., Rascati, K. L., Brown, C. M., Barner, J. C. et al. (2003). Ethnic differences in use of antipsychotic medication among Texas Medicaid clients with schizophrenia. /. Clin. Psychiatry, 64, 635-9. 

Lindamer, L., Lacro, J. P. Jeste, D.V. (1999). Relationship of ethnicity to the effects of antipsychotic medication. In J. M. Herrara, W. B. Lawson and J. J. Sramek, eds., Cross Cultural Psychiatry. Sussex John Wiley Sons. 

Green, M. F. Braff, D. L. (2001). Translating the basic and clinical cognitive neuroscience of schizophrenia to drug development and clinical trials of antipsychotic medications. Biol. 

---