Cardiovascular effects antipsychotic drugs

Dopamine is the immediate precursor in the synthesis of norepinephrine (see Figure 6-5). Its cardiovascular effects were described above. Endogenous dopamine may have more important effects in regulating sodium excretion and renal function. It is an important neurotransmitter in the central nervous system and is involved in the reward stimulus relevant to addiction. Its deficiency in the basal ganglia leads to Parkinson s disease, which is treated with its precursor levodopa. Dopamine receptors are also targets for antipsychotic drugs. 

Benzodiazepines are used as hypnotics because they have the ability to increase total sleep time. They demonstrate minimal cardiovascular effects, but do have the ability to increase heart rate and decrease cardiac output. Most CNS depressants, including the benzodiazepines, exhibit the ability to relax skeletal muscles. Clozapine, a dibenzodiazepine, is used in the treatment of schizophrenia. It has both sedative and antipsychotic actions, and is the only FDA-approved medication indicated for treatment-resistant schizophrenia, and for reducing the risk of suicidal behavior in patients with schizophrenia. This drug can have potentially life-threatening side effects, but appears to have no abuse potential and will not be considered further. 

Selective serotonin reuptake inhibitors (SSRIs) are a type of antidepressant that stimulates the pineal gland s ability to produce melatonin. Antipsychotic drugs also have this effect. Other medicines have the opposite effect. Certain types of medicines used to treat cardiovascular disease called beta blockers reduce the production of melatonin by the pineal gland. Nonsteroidal antiinflammatories, which are used to treat pain and/or fever,... 

Barbiturate overdose may be treated with gastric lavage and oral administration of activated charcoal. Supportive therapy of cardiovascular, respiratory, and renal function also should be provided. Coadministration of alcohol and barbiturates may increase the sedative effect of chloral hydrate. Long-term use of barbiturates leads to dependence. Sudden discontinuation of an antipsychotic drug may cause withdrawal symptoms such as nausea, vomiting, anorexia, diarrhea, rhinorrhea, sweating, insomnia, restlessness, and vertigo.151... 

During 2004 a number of clinical trials were reported involving acute and maintenance studies of lithium, mostly either comparing new atypical antipsychotic drugs with lithium in bipolar disorder or in combined treatment studies. Of the relatively few studies of the adverse effects of lithium, most clustered in the areas of cardiovascular effects and issues regarding lithium toxicity. 

Buckley NA, Sanders P. Cardiovascular adverse effects of antipsychotic drugs. Drug Saf 2000 23(3) 215-28. 

Americans (26). It is involved in the metabolism of approximately 30-40 commonly used drugs. Millions of patients with compromised metabolism are thus at risk of adverse drug reactions when prescribed drugs that are CYP2D6 substrates. Many such drugs are used for treating psychiatric (such as antidepressants and antipsychotics) and cardiovascular diseases (such as j8-blockers and antiar-rhythmics), where the therapeutic window can be narrow and side effects common. 

Clozapine, which is associated with higher risk of agranulocytosis and seizures, is indicated (25 mg once or twice daily) only in the management of schizophrenic patients who fail to respond adequately to standard antipsychotic drug treatment. On the other hand, it is relatively free from extrapyramidal side effects such as parkinsonism. Approximately 50% of the administered dose is excreted in the urine and 30% in the feces as inactive demethylated, hydroxylated, and N-oxide derivatives. Clozapine has anticholinergic properties and causes tachycardia, and hence poses a serious risk for a patient with compromised cardiovascular function (see also Table 23). 

This syndrome is a combination of symptomatic effects produced by antipsychotic drug therapy. Symptoms and signs include hyperpyrexia, muscle rigidity, altered mental status (e.g., catatonia) and cardiovascular instability (e.g., unstable heart rate and blood pressure). Acute renal failure may ultimately occur. Diagnostic signs include elevated creatine phosphokinase (CPK) and myoglobinuria. 

Other autonomic effects of antipsychotic drugs are probably mediated by the hypothalamus, such as an impairment of the body s abihty to regulate temperature. Clozapine can induce moderate elevations of body temperature that can be confusing clinically central effects on temperatme regulation and cardiovascular and respiratory function probably contribute to the featmes of neuroleptic malignant syndrome (see Table 18-1). 

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