Second-generation atypical

3 Second-generation ( atypical ) antipsychotic drugs (SGAs) -amisulpiride, aripiprazole, clozapine and olanzapine 

Carbarn azepine (may enhance the risk of bone marrow supression when combined with clozapine) 

Drugs whose serum levels/effects can be increased by SGAs 

Drugs that can cause significant and severe side-effects due to additive impact (not due to toxicity) 

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TABLE 34-10. Monitoring Protocol for Patients on Second-Generation (Atypical) Antipsychotics... 

The first of the second-generation, or atypical, antipsychotics was clozapine. Clozapine (Clozaril) is relatively free of the movement disorders that characterize the first-generation drugs. This is true of, and defines, second-generation, atypical antipsychotics. It was a significant breakthrough for schizophrenia patients. 

Second-generation (atypical) antipsychotics include clozapine, olanzapine, quetiapine, risperidone, aripiprazole. 

Second-generation (atypical) antipsychotic drugs - mechanism of action... 

Treatment of Major Depression. Dmgs commonly used for the treatment of depressive disorders can be classified heuristicaHy iato two main categories first-generation antidepressants with the tricycHc antidepressants (TCAs) and the irreversible, nonselective monoamine—oxidase (MAO) inhibitors, and second-generation antidepressants with the atypical antidepressants, the reversible inhibitors of monoamine—oxidase A (RIMAs), and the selective serotonin reuptake inhibitors (SSRIs). Table 4 fists the available antidepressants. 

Second generation COMT inhibitors were developed by three laboratories in the late 1980s. Apart from CGP 28014, nitrocatechol is the key structure of the majority of these molecules (Fig. 3). The current COMT inhibitors can be classified as follows (i) mainly peripherally acting nitrocatechol-type compounds (entacapone, nitecapone, BIA 3-202), (ii) broad-spectrum nitrocatechols having activity both in peripheral tissues and the brain (tolcapone, Ro 41-0960, dinitrocatechol, vinylphenylk-etone), and (iii) atypical compounds, pyridine derivatives (CGP 28014,3-hydroxy-4-pyridone and its derivatives), some of which are not COMT inhibitors in vitro but inhibit catechol O-methylation by some other mechanism. The common features of the most new compounds are excellent potency, low toxicity and activity through oral administration. Their biochemical properties have been fairly well characterized. Most of these compounds have an excellent selectivity in that they do not affect any other enzymes studied [2,3]. 

Current antipsychotics used to treat patients are divided into two classes the first generation antipsychotics (FGA) or typicals (e.g., chlorproma-zine, haloperidol, thioridazine, and loxapine) and the second generation antipsychotics (SGA) or atypicals (i.e., clozapine, olanzapine, quetiapine, risperidone, aripiprazole, ziprasidone, and asenapine). 

Atypical antipsychotics The second generation or so-called atypical antipsychotics have chemical, pharmacological, and clinical properties that are different from those of the classical antipsychotics/ neuroleptics. The most commonly used atypicals include clozapine, olanzapine, risperidone, and quetiapine. 

There are four classes of antidepressants tricyclic antidepressants (imipramine, trimipramine, amitriptyline, doxepin, desipramine, protriptyline, nortriptyline, amoxapine, maprotiline) monoaminooxidase (MAO) inhibitors (phenelzine, isocarboxazid, tranylcypromine) second-generation antidepressants or atypical antidepressants, which are a chemically dissimilar group of recently proposed drugs (bupropion, trazodone, fluoxetine) and amphetamines and other stimulators of the CNS (dextroamphetamine, methylphenidate). 

The conventional antipsychotics have little effect on the negative psychotic symptoms such as autism, stupor and emotional withdrawal. The so-called atypical antipsychotics, or second-generation antipsychotics, like the heterocyclic compound risperidone, the benzamide sulpiride and several diben-zepines of which clozapine is the best known, have a broader spectrum which means that they also have an effect on the negative psychotic symptoms. Most share a common attribute of working on serotonin receptors as well as dopamine receptors. They have a low risk of extrapyramidal side effects. 

In the late 1980s, clozapine a chlorpromazine like compound with a multiplicity of effects was rediscovered and termed an atypical neuroleptic. It appears to be the only genuinely atypical agent - that is an agent with significant beneficial treatment effects in the absence of EPS (see Wahlbeck et ah, 1999). A second generation of antipsychotics have succeeded clozapine been marketed as being atypical. 

The effectiveness of the second generation antipsychotics (now called atypicals, because they have weak D2 blocking properties) show that this concept is not valid. Drugs like clozapine do not cause the Parkinsonian side effects even though they are very successful in terminating psychosis. 

The safety of antidepressants should be the first priority for the elderly. For this reason, the second-generation antidepressants, or the atypical tricyclic antidepressant lofepramine, should be the drugs of choice. Undoubtedly the SSRI antidepressants have a major role to play and of these, citalopram and fluvoxamine have been extensively studied in the elderly depressed patient. 

Since the 1990s a range of new compounds have been introduced for the treatment of psychosis and schizophrenia. Although these compounds vary significantly in their pharmacological actions, they are collectively referred to as atypical antipsychotics or second-generation antipsychotics. The property they are all supposed to share is a lower... 

On occasion, research studies directly confirm the brain-disabling principle, but without intending to do so and without acknowledging it. In some ways, this is the most objective kind of research in that the researchers are unaware of the principle that they are testing. The following three studies involve the second-generation or atypical neuroleptic risperidone (Risperdal), which is widely prescribed to children and adults. 

An important leap in the treatment of schizophrenia occurred in the late 1980s with the introduction of the first of a number of medications that offered a wider spectrum of action and relatively improved tolerability. Some of these atypical antipsychotics, also called second-generation antipsychotics, are listed in Table 5.13. 

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