Thioridazine retinal

Thioridazine retinal pigmentation at high doses, sexual dysfunction. 

Retinitis pigmentosa can result from thioridazine doses greater than 800 mg daily (the recommended maximum dose) and can cause permanent visual impairment or blindness. 

Thioridazine poses a potentially greater danger to the eyes than CPZ. At doses greater than 800 mg/day, a retinitis pigmentosa may appear, leading to substantial visual impairment or even blindness. In some cases, the condition does not fully remit when the drug is stopped therefore, thioridazine doses of more than 800 mg/day are never recommended to allow for a reasonable margin of safety (499). 

Deposits in the anterior portions of the eye (cornea and lens) are a common complication of chlorpromazine therapy. They may accentuate the normal processes of aging of the lens. Thioridazine is the only antipsychotic drug that causes retinal deposits, which in advanced cases may resemble retinitis pigmentosa. The deposits are usually associated with "browning" of vision. The maximum daily dose of thioridazine has been limited to 800 mg/d to reduce the possibility of this complication. 

A 28-year-old woman with a long history of psychiatric problems was taking fluoxetine, diazepam, methylphe-nidate, and thioridazine 800 mg qds (17). Fluorescein angiography showed confluent areas of punctate hyperfluorescence, consistent with diffuse retinal pigment epithelial alteration secondary to acute thioridazine toxic effects. 

Chlorpromazine (Thorazine) and thioridazine (Mellaril), both phenothiazine derivatives, are used for their antipsychotic effects in the control of severely disturbed or agitated behavior and in schizophrenia. Thioridazine has a higher incidence of antimuscarinic effects but a lower incidence of extrapyramidal symptoms. Pigmentary changes of the retina have been reported occasionally in association with chlorpromazine therapy, although it is recognized that only thioridazine produces retinal toxicity. 

Thioridazine can cause significant retinal toxicity, leading to reduced visual acuity, changes in color vision, and disturbances of dark adaptation.These symptoms typically occur 30 to 90 days after initiation of treatment. The fundus often appears normal during the early stages of symptoms, but within several weeks or months a pigmentary... 

Figure 35-11 Retinal pigment epithelial hyperplasia and atrophy in 33-year-old man with thioridazine retinopathy.

It is now recognized that the primary clinical fector associated with thioridazine retinopathy is the daily dose of drug. Before becoming aware of the dose-related retinal toxicity, dosages exceeding 1,600 mg daily were commonly prescribed. Few cases of pigmentary retinopathy have been reported, however, with daily dosages of less than 800 mg. 

Eye. Toxic cataract can be due to chloroquine and related drugs, adrenal steroids (topical and systemic), phenothiazines and alkylating agents. Comeal opacities occur with phenothiazines and chloroquine. Retinal injury occurs with thioridazine (particularly, of the antipsychotics), chloroquine and indomethacin. 

Because of cataract development and lenticular changes in animals, baseline and periodic eye exams are recommended in the product labeling for patients receiving quetiapine. However, clinical experience with quetiapine since marketing has not supported a significant risk of cataracts. Retinitis pigmentosa can result from use of thioridazine doses greater than 800 mg daily. It is caused by melanin deposits, and can result in permanent visual impairment or blindness. There is no evidence that it is a function of cumulative dose. ... 

Thioridazine -H-+ -f H- +++ Low potency, phenothiazine, retinal deposits, cardiotoxicity (torsades— quinidine-like )... 

Answer C. Ocular toxicity is characteristic of chloroquine and hydroxychloroquine. Corneal deposits are reversible, but retinal pigmentation can ultimately lead to blindness. Patients will complain about GI distress, visual dysfunction, ringing in the ears (note that tinnitus aiso occurs in salicylism), and itchy skin. Hydroxychloroquine also promotes oxidative stress that can lead to hemolysis in G6PD deficiency. DMARDs include gold salts (e.g., auranofin), methotrexate, and etanercept, but thioridazine is a phenothiazine used as an antipsychotic it lacks anti-inflammatory effect, but does cause retinal pigmentation. 

Miscellaneous toxidties Visual impairment caused by retinal deposits has occurred with thioridazine at high doses, this drug may also cause severe conduction defects in the heart that result in fatal ventricular arrhythmias. Sertindole prolongs the QT interval of the ECG the underlying myocardial effect may lead to cardiac arrhythmias. Clozapine causes a small but important (1—2%) incidence of agranulocytosis and at high doses has caused seizures. 

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). 

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