Thioridazine arrhythmia with

Atropine-like side effects are more prominent with thioridazine than with other phenothi-azines. but the drug is less likely to cause extrapyramidal dysfunction. At high doses, thioridazine causes retinal deposits which in advanced cases resemble retinitis pigmentosa. The patient may complain of browning of vision. The drug has quinidine-like actions on the heart and, in overdose, may cause arrhythmias and cardiac conduction block. The answer is (E). 

Hypersensitivity to the drug or any other component of the product (cross-sensitivity between phenothiazines may occur) comatose or greatly depressed states caused by CNS depressants or from any other cause (phenothiazines, clozapine, loxapine, molindone, pimozide, haloperidol) coadministration with other drugs that prolong the QT interval and in patients with congenital long QT syndrome or history of cardiac arrhythmias (mesoridazine, thioridazine, pimozide, ziprasidone see Drug..Interactions). 

Ziprasidone, pimozide, mesoridazine, and thioridazine have been shown to prolong the QT interval, and drugs with this potential have been associated with torsade de pointes-type arrhythmias and sudden death. Perform a baseline ECG and measure serum potassium and magnesium before initiation of treatment and periodically during treatment, especially during a period of dose adjustment. Patients with QT interval over 450 msec should not receive mesoridazine or thioridazine. Avoid ziprasidone in patients with histories of significant cardiovascular illness (eg. 

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. 

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. 

Thioridazine in doses exceeding 300 mg daily is almost always associated with minor abnormalities of T waves that are easily reversible. Overdoses of thioridazine are associated with major ventricular arrhythmias, eg, torsade de pointes, cardiac conduction block, and sudden death it is not certain whether thioridazine can cause these same disorders when used in therapeutic doses. In view of possible additive antimuscarinic and quinidine-like... 

Amaral et al. [3] prepared a review providing cogent evidence that both intracellular multidrug-resistant tuberculosis (MDRTB) and intracellular methicillin-resistant Staphylococcus aureus (MRSA) can be killed by concentrations of thioridazine in the medium that is below that present in the plasma of the patients treated with this agent. Although thioridazine has been claimed to cause arrhythmias and even sudden death, the frequencies of those episodes are rare and, when present, they are related to a patient s underlying cardiac status, as opposed to the direct effect of the agent itself. 

Connolly MJ, Evemy KL, Snow MH. Torsade de pointes ventricular tachycardia in association with thioridazine therapy report of two cases. New Trends Arrhythmias 1985 1 157. 

EKGs may be useful for selected patients (e.g., those with personal or family history of QTc prolongation cardiac arrhythmia recent myocardial Infarction uncompensated heart failure or taking agents that prolong QTc Interval such as pimozide, thioridazine, selected antlarrhythmics, moxifloxacin, spartloxacin, etc.)... 

Thioridazine can increase the QTc interval and potentially cause torsades de pointes-type arrhythmia or sudden death, especially in combination with drugs that raise its levels... 

Interactions. Several types of drug interfere with lithium excretion by the renal tubules, causing the plasma concentration to rise. These include diuretics (thiazides more than loop type), ACE inhibitors and angiotensin-11 antagonists, and nonsteroidal anti-inflammatory analgesics. Theophylline and sodium-containing antacids reduce plasma lithium concentration. The effects can be important because lithium has such a low therapeutic ratio. Diltiazem, verapamil, carbamazepine and pheny-toin may cause neurotoxicity without affecting the plasma lithium. Concomitant use of thioridazine should be avoided as ventricular arrhythmias may result. 

Because of its potent anticholinergic properties, thioridazine shonld be used cautiously in patients with cardiac diseases snch as congestive heart failure, arrhythmias, angina pectoris, or heart block in encephalitis, Reye s syndrome, head injnry, respiratory disease, epilepsy and other seizure disorders, glaucoma, prostatic hypertrophy, urinary retention, Parkinson s disease, and pheochromocytoma because the drug may exacerbate these conditions and in hypocalcemia because it increases the risk of extrapyramidal reactions. 

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