Blood with antipsychotics

Neuroleptic malignant syndrome (NMS) A potentially fatal symptom complex sometimes referred to as NMS has been reported in association with promethazine alone or in combination with antipsychotic drugs. Clinical manifestations of NMS are hyperpyrexia, muscle rigidity, altered mental status, and evidence of autonomic instability (eg, irregular pulse or blood pressure, tachycardia, diaphoresis, cardiac dysrhythmias). 

Gl dysmotility Esophageal dysmotility and aspiration have been associated with antipsychotic drug use. Use quetiapine, ziprasidone, risperidone, olanzapine, aripiprazole, and others cautiously in patients at risk for aspiration pneumonia. Hypersensitivity reactions Patients who have demonstrated a hypersensitivity reaction (eg, blood dyscrasias, jaundice) with a phenothiazine should not be re-exposed to any phenothiazine unless the potential benefits of treatment outweigh the possible hazards. 

SSRIs are often prescribed with antipsychotic drugs, and some SSRIs inhibit CYP2D6, which can lead to increased blood concentrations of the antipsychotic drug. In 13 patients aged 26-56 years with schizophrenia, stabilized on risperidone 4-6 mg/day who took sertraline 50 mg/day for 4 weeks, plasma concentrations of risperidone and its major metabolite, 9-OH-risperidone, did not change... 

Much of the study of interethnic differences in the pharmacokinetics and pharmacodynamics of psychotropic medications has involved TCAs and differences between Asians and Caucasians (Pi et al. 1993a). As with antipsychotics, there are clinical reports that Asians require lower doses of TCAs (Pi and Gray 1998 Pi et al. 1993a). It has also been suggested that Asians show a therapeutic response at lower blood levels of TCAs (Yamashita and Asano 1979), suggesting pharmacodynamic differences. Other studies of prescribing patterns have failed to confirm this and found that the daily doses of amitriptyline, imipramine, doxepin, and nortriptyline prescribed by psychiatrists at 29 medical schools in 9 Asian countries were the same as those used in the United States (Pi et al. 1985). It was also reported that Asians and whites need similar doses of at least 150 mg/day to attain recommended therapeutic blood concentrations (Kinzie et al. 1987). 

Blood Dyscrasias Mild leukocytosis, leukopenia, and eosinophilia occasionally occur with antipsychotic treatment, particularly with clozapine and less often with phenothiazines of low potency. It is difficult to determine whether leukopenia that develops during the administration of such agents is a forewarning of impending agranulocytosis. This serious comphcation occurs in not more than 1 in 10,000 patients receiving chlorpromazine or other low-potency agents (other than clozapine) it usually appears within the first 8-12 weeks of treatment. 

Li often is used in conjunction with antipsychotic, sedative, antidepressant, and anticonvulsant drugs. Case reports suggesting a risk of increased CNS toxicity when Li is combined with haloperidol are at variance with many years of experience with this combination. Antipsychotic drugs may prevent nausea, which can be an early sign of Li toxicity. There is no absolute contraindication to the concurrent use of LT and psychotropic drugs. Finally, anticholinergic and other agents that alter GI motility also may alter LT concentrations in blood over time. 

Overdose with phencyclidine is dangerous. The basic principles of treatment are to maintain ventilation and to control seizures, blood pressure, and hyperthermia. Phencyclidine is secreted into the stomach, so removal of the drug may be hastened by activated charcoal or continual nasogastric suction. Phencyclidine is a weak base, and its renal elimination may be accelerated by urinary acidification. Treatment with antipsychotic drugs may be appropriate if psychotic symptoms follow the acute intoxication. The answer is (E). 

The antipsychotics are contraindicated in patients with known hypersensitivity to the drug s, in comatose patients, and in those who are severely depressed, have bone marrow depression, blood dysera ias, Parkinson s disease (haloperidol), liver impairment, coronary artery disease, or severe hypotension or hypertension. 

There is an increased risk of sedation and delirium with increased age. There is also an increased risk of antidopaminergic effects such as parkinsonism due to antipsychotic drugs. Many other drugs that pass the blood-brain barrier may cause adverse effects in the elderly. The response of opioids may be increased in the elderly, resulting in oversedation (Turnheim 1998). 

Many antipsychotics show great interindividual variation in plasma levels and so analysis of therapeutic levels can be important clinically as well as in the research laboratory. In addition, nonresponse to the drugs may actually be due to excessive levels of neuroleptics, a paradoxical situation that requires analysis to identify (Rockland, 1986). Several methods using FID were cited in the previous edition of the Handbook of Neurochemistry but ECD and NPD have both shown utility for the typically low therapeutic levels (Cooper, 1988). GC-FID has been used to analyze levels of clozapine in blood, gastric, and urine samples in fatal cases of overdose with this drug (Ferslew et al., 1998), and olanzapine has been measured in blood and urine samples by GC-NPD in overdoses (Stephens et al., 1998). 4-(4-Chlorophenyl)-4-hydroxypiperidine, a metabolite of haloperidol, was analyzed in urine, plasma, brain, and liver from haloperidol-treated rats by GC-ECD, after derivatization with PFBC under aqueous conditions (Fang et al., 1996). 

What are the best treatments for resistant schizophrenia If the disease has shown little or no improvement with the previous antipsychotics, then a trial of clozapine is warranted. This is a difficult and expensive medication that reqnires a motivated patient who is willing to report for weekly blood draws. Taken altogether, clozapine is a difficult drug. Nevertheless, it is the one antipsychotic that has clearly been shown to help schizophrenia that is resistant to other antipsychotics. 

But there are patients with ADHD who continue to have problems with impulsiv-ity despite these treatments. This has led to several innovative approaches to help address these residual symptoms with medications ranging from antidepressants to mood stabilizers, antipsychotics, and even medicines that are more commonly used to treat high blood pressure. The problem here is finding a medication that will alleviate the remaining impulsivity without worsening the problems with attention. There has been modest success with these more difficult cases, but there remains room for improvement. 

Carbamazepine is more widely used for treating chronically agitated dementia patients. Its onset of action is delayed by several days to a couple of weeks therefore, other tranquilizing medications such as antipsychotics may need to be used when first starting carbamazepine. Carbamazepine doses have problematic side effects that require blood monitoring, and it also interacts with many medications. 

Of all these treatments, the only consistent improvement is seen with the atypical antipsychotic clozapine (Clozaril). Treatment-resistant TD is in fact one generally accepted indication for nsing clozapine. However, becanse of the expense of this drug, the risk for granulocytopenia, and the reqnirement for biweekly blood draws, other measures should hrst be tried. 

Unfortunately, few of the studies that have attempted to relate the blood concentrations of neuroleptics to therapeutic response have fulfilled all these criteria. There is a suggestion that a "thera peutic window" exists for some phenothiazine neuroleptics. A therapeutic window is a range of concentrations of a drug measured in the blood that are associated with a good therapeutic response. Plasma concentrations outside this range are either too low to ensure a therapeutic response or so high that they induce toxic side effects. Despite the numerous studies of the relationship between the plasma concentration and the therapeutic response for a number of "standard" neuroleptics, it would appear that such correlations rarely account for more than 25% of the variance in clinical response to treatment. The existence of a therapeutic window for neuroleptics would therefore appear to be unproven. However, there could be ranges of plasma concentrations associated with optimal antipsychotic action, but these... 

Encephalopathic syndrome - An encephalopathic syndrome (characterized by weakness, lethargy, fever, tremulousness, confusion, extrapyramidal symptoms, leukocytosis, elevated serum enzymes, blood urea nitrogen, fasting blood sugar) has occurred in a few patients treated with lithium plus an antipsychotic (haloperidol). 

---