Antipsychotics cardiac effects

Clozapine also produces nonspecific inverted T waves, but again, this is not considered clinically relevant. As far as is known, abrupt discontinuation of antipsychotics, including clozapine, does not produce serious adverse cardiac effects, although common sense dictates a gradual reduction over several days ( 39). 

Ari pi prazole, olanzapine, quetiapine, risperidone, and ziprasidone are effective as monotherapy or as add-on therapy to lithium or valproate for acute mania. Prophylactic use of antipsychotics can be needed for some patients with recurrent mania or mixed states, but the risks versus benefits must be weighed in view of long-term side effects (e.g., obesity, type 2 diabetes, hyperlipidemia, hyperprolactinemia, cardiac disease, and tardive dyskinesia). 

Sertindole is one of the newer antipsychotic medications available. It is classified chemically as a phenylindole derivative and has activity at dopamine and serotonin receptors. It is not associated with sedative effects. Sertindole was voluntarily withdrawn from the market late 1998 due to concerns over the risk of cardiac arrhythmia s. The European Commission recommended lifting the marketing restrictions on sertindole in 2005 with a regulatory requirement of ECG monitoring. 

Contraindications for antipsychotic therapy are few they may include Parkinson s disease, hepatic failure, hypotension, bone marrow depression, or use of CNS depressants. Overdoses of antipsychotics are rarely fatal, except for thioridazine, which is associated with major ventricular arrhythmias, cardiac conduction block, and sudden death. For other agents gastric lavage should be attempted even if several hours have elapsed since the drug was taken, because gastrointestinal motility is decreased and the tablets may still be in the stomach. Moreover, activated charcoal effectively binds most of these drugs and can be followed by a saline cathartic. The hypotension often responds to fluid replacement or pressor agents such as norepinephrine. 

In pharmacodynamic interactions, the pharmacological effect of a drug is changed by the action of a second drug at a common receptor or bioactive site. For example, low-potency antipsychotics and tertiary amine TCAs have anticholinergic, antihistaminic, a-adrenergic antagonist, and quinidine-Kke effects. Therefore, concurrent administration of chlorpromazine and imipramine results in additive sedation, constipation, postural hypotension, and depression of cardiac conduction. 

Atypical antipsychotics cause fewer EPS than do conventional antipsychotics. Clozapine and quetiapine are the least likely to cause EPS and are therefore recommended for treatment of psychosis in patients with Parkinson s disease. With the notable exception of risperidone, atypical antipsychotics cause substantially less hyperprolactinemia than do conventional antipsychotics. Weight gain is a side effect of all atypical antipsychotics except ziprasidone and aripiprazole. Concerns about cardiac conduction delay with ziprasidone therapy exist and warrant consideration in patients who have... 

Assessment of physical, as well as psychiatric status, is also critically important. The presence of intercurrent medical disorders, as well as any medication used to manage them, increases the likelihood of an adverse outcome with an otherwise appropriate medication. With a recent history of myocardial infarction, certain tricyclic antidepressants (TCAs) or low-potency antipsychotics might be contraindicated due to potential adverse effects on cardiac function. Another example is the avoidance of carbamazepine in a bipolar patient with a persistently low white blood cell count. Finally, b-blockers are typically contraindicated in a patient with asthma. 

In a report of 122 elderly patients on risperidone, hypotension was noted in 28.7% and symptomatic orthostatic hypotension was noted in 9.8%. Significant decreases in blood pressure occurred with risperidone treatment (p = 0.0001) and were common in patients with cardiovascular disease and those taking an SSRI or valproate (p = 0.03) (502). Hence, like other antipsychotics, risperidone should be prescribed cautiously for elderly patients and those with preexisting cardiac disease. Its hypotensive versus its orthostatic hypotensive effects may be an age-related pharmacodynamic response. Blood pressure, including orthostatic blood pressure, should be monitored routinely until the risperidone dosage is stabilized. Furthermore, when risperidone therapy is initiated in the elderly, dosage should be titrated from 0.25 to 0.5 mg two times a day with increments of 0.25 to 0.5 mg weekly (92). 

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. 

In the development of new antipsychotics, cQT intervals are routinely evaluated but it is currently unclear how predictive these are of clinically significant cardiotoxicity or sudden death. For this reason, the heart rate variability (HRV) index has been developed. It has been shown that the HRV decreases after TCAs and clozapine. In a comparison of the acute effects of olanzapine, risperidone and thioridazine in healthy male volunteers, olanzapine was shown to increase, thioridazine to decrease while risperidone was without effect on the HRV. A decrease in the HRV is an established predictor of poor cardiac outcome. The cardiac changes were unrelated to the degree of sedation caused by the drugs. 

In the 1950s, a more evidence-based approach to antipsychotic drug (AP) therapy was undertaken when structural variations of antihistamines were produced by a French scientist (Paul Charpentier), in order to make use of the unwanted sedative side effect produced by these drugs. Initially used to lower body temperature in patients undergoing cardiac surgery, chlorpromazine (Fig. II) was the first drug with antipsychotic properties successfully used in clinical trials [3],... 

Interactions The vitamin pyridoxine (B6) increases the peripheral breakdown of levodopa and diminishes its effectiveness (Figure 8.6). Concomitant administration of levodopa and monoamine oxidase (MAO) inhibitors, such as phenelzine (see p. 124), can produce a hypertensive crisis caused by enhanced catecholamine production therefore, caution is required when they are used simultaneously. In many psychotic patients, levodopa exacerbates symptoms, possibly through the buildup of central amines. In patients with glaucoma, the drug can cause an increase in intraocular pressure. Cardiac patients should be carefully monitored because of the possible development of cardiac arrhythmias. Antipsychotic drugs are contraindicated in parkinsonian patients, since these block dopamine receptors and produce a parkinsonian syndrome themselves. 

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