Cardiac arrhythmias antipsychotics

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. 

Examples of recent work carried out by the DSRU includes the examination of mortality rates and cardiac arrhythmias between sertindole and two other at)q)ical antipsychotics, olanzapine and risperidone. Tolterodine, an agent often used for urinary frequency and bladder instability, is the latest drug to be examined by the DSRU.135... 

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 Sertindole was voluntarily withdrawn from the market late 1998 due to concerns over the risk of cardiac arrhythmia s. The European Commission recommended lifting the marketing restrictions on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. 

Women also have a higher risk of developing drug-induced cardiac arrhythmia (Ebert et al., 1998) and life-threatening torsades de points arrhythmia may occur with drugs such as antihistamines, antibiotics or antipsychotics, making it important that Cardiac QT studies be conducted in volunteers of both genders (Woolsey, 2005). 

Amphetamines (release Cocaine (prevent re-uptake of DA) Euphoria, hypervigilance, Anxiety, stereotyped behavior, grandiosity, paranoia, tachycardia, pupillary dilation Depression, fatigue, f fkX- CwiSrbictioi Noradrenaline system, NAC pathway (dopaminergic) 1 Antipsychotics or benzodiazepines bromocriptine, amantadine, desipramine Increased use among white professionals, cardiac arrhythmias... 

Mesoridazine, a metabolite of thioridazine, is thought to exert its antipsychotic effects by postsynaptic blockade of CNS dopamine receptors, thereby inhibiting dopamine-mediated effects. Mesoridazine has many other central and peripheral affects it produces both alpha and ganglionic blockade and counteracts histamine- and serotonin-mediated activities. Mesoridazine and thioridazine cause fewer movement disorders (see Phenotheazine Derivatives). Mesoridazine is metabolized to inactive metabolites, which are excreted by the kidneys. Overdosage of mesoridazine causes CNS depression characterized by deep, unarousable sleep, convulsive seizures, and cardiac arrhythmias (see also Table 2). 

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. 

Liperoti R, Gambassi G, Lapane KL, Chiang C, Pedone C, Mor V, Bernabei R. Conventional and atypical antipsychotics and the risk of hospitalization for ventricular arrhythmias or cardiac arrest. Arch Intern Med 2005 165 696-701. 

LOOP DIURETICS ANTIPSYCHOTICS- ATYPICALS, PHENOTHIAZINES, PIMOZIDE Risk of arrhythmias Cardiac toxicity directly related to hypokalaemia Monitor potassium levels every 4-6 weeks until stable, then at least annually... 

Concomitant use of pimozide with quinidine, procainamide, disopyramide, and other antiarrhythmics, phenothi-azines (other antipsychotics), and antidepressants may further depress cardiac conduction and prolong the Q-T interval, resulting in serious arrhythmias. 

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