Antipsychotics cardiovascular effects

High-potency antipsychotic with a relatively high incidence of EPS, but a low incidence of sedation, anticholinergic effects, and cardiovascular effects... 

Antipsychotic agents may have several cardiovascular effects. Medication-induced hypotension is generally more problematic with lower-potency neuroleptics than with other antipsychotics and appears to be mediated through tti-adrenergic blockade. Besides increases in heart rate that may be the result of hypotension, antipsychotics with appreciable anticholinergic effects (see Clinical Implications, below) can lead to tachycardia (Gutgesell et ah, 1999). 

Cardiovascular effects. Hypotension and tachycardia occur in most patients taking clozapine. Cases of potentially fatal myocarditis and dilated cardiomyopathy have been reported in association with clozapine (Kilian et al. 1999). Myocarditis typically occurred within 3 weeks of starting clozapine, but cardiomyopathy may not be apparent for several years. Although rare, treatment-emergent myocarditis and cardiomyopathy occur at a reportedly higher incidence with clozapine than with other antipsychotics (Coulter et al. 2001). The mechanism by which clozapine may cause myocarditis has not been established, but some authors have speculated that clozapine may cause an immunoglobuhn E (IgE)-mediated type 1 hypersensitivity reaction (Kihan et al. 1999) or a hypereosinophilic syndrome (Hagg et al. 2001). 

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. 

Antipsychotic tranquilizers Increased sedation. Variable effects on respiratory depression. Accentuation of cardiovascular effects (antimuscarinic and -blocking actions). 

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. 

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. 

What are the cardiovascular effects seen with the phenothiazine class of antipsychotics ... 

Adverse Cardiovascular and Cerebrovascular Effects The most common adverse cardiovascular effect is orthostatic hypotension, which may result in syncope, falls, and injuries. Hypotension is most likely to occur with administration of the phenothiazines with aliphatic side chains or atypical antipsychotics. Potent neuroleptics generally produce less hypotension. 

Cardiovascular side effects. Ziprasidone produced a mean QTc prolongation of 21 ms at maximal blood levels achieved with typical therapeutic doses. However, in all clinical trials, the rate of QTc intervals greater than 500 ms (considered a threshold for arrhythmia risk) did not differ from the rate associated with placebo (<0.1%). The QTc effect of ziprasidone is larger than that of other atypical antipsychotics but smaller than that of thioridazine. Blood levels of ziprasidone increased about 40% when ketoconazole (a metabolic inhibitor) was coadministered, and no change in QTc duration was detected. 

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). 

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... 

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