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Quinine is an optical isomer of quinidine. Quinine was once widely used for treatment of malaria and is still occasionally used for chloroquine-resistant cases. Quinine was formerly widely prescribed for the treatment of nocturnal muscle cramps, but an FDA advisory in 2006 warned that the modest benefits are outweighed by its potential to cause severe toxicity, and its use is no longer recommended for this indication. Quinine is found in tonic water and has been used to cut street heroin. It has also been used as an abortifacient.

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  1. Mechanism of toxicity

    1. The mechanism of quinine toxicity is believed to be similar to that of quinidine (See Quinidine and Other Type IA Antiarrhythmic Drugs); however, quinine is a much less potent cardiotoxin.

    2. Quinine also has toxic effects on the retina that can result in blindness. At one time, vasoconstriction of retinal arterioles resulting in retinal ischemia was thought to be the cause of blindness; however, recent evidence indicates a direct toxic effect on photoreceptor and ganglion cells.

    3. Pharmacokinetics (see Table II–61)

  2. Toxic dose. Quinine sulfate is available in capsules and tablets containing 130–325 mg. The minimum toxic dose is approximately 3–4 g in adults; 1 g has been fatal in a child.

  3. Clinical presentation. Toxic effects involve the cardiovascular and central nervous systems, the eyes, and other organ systems.

    1. Mild intoxication produces nausea, vomiting, and cinchonism (tinnitus, deafness, vertigo, headache, and visual disturbances).

    2. Severe intoxication may cause ataxia, confusion, obtundation, convulsions, coma, and respiratory arrest. With massive intoxication, quinidine-like cardiotoxicity (hypotension, QRS- and QT-interval prolongation, atrioventricular [AV] block, and ventricular arrhythmias) may be fatal.

    3. Retinal toxicity occurs 9–10 hours after ingestion and includes blurred vision, impaired color perception, constriction of visual fields, and blindness. The pupils are often fixed and dilated. Funduscopy may reveal retinal artery spasm, disc pallor, and macular edema. Although gradual recovery occurs, many patients are left with permanent visual impairment.

    4. Other toxic effects of quinine include hypokalemia, hypoglycemia, hemolysis (in patients with glucose-6-phosphate dehydrogenase [G6PD] deficiency), and congenital malformations when used in pregnancy.

  4. Diagnosis is based on a history of ingestion and the presence of cinchonism and visual disturbances. Quinidine-like cardiotoxic effects may or may not be present.

    1. Specific levels. Serum quinine levels can be measured by the same assay as for quinidine, as long as quinidine is not present. However, most hospital-based clinical laboratories no longer offer these assays. Plasma quinine levels above 10 mg/L have been associated with visual impairment; 87% of patients with levels above 20 mg/L reported blindness. Levels above 16 mg/L have been associated with cardiac toxicity.

    2. Other useful laboratory studies include CBC, electrolytes, glucose, BUN, creatinine, arterial blood gases or oximetry, and ECG monitoring.

  5. Treatment

    1. Emergency and supportive measures

      1. Maintain an open airway and assist ventilation if necessary (See Airway and Breathing).

      2. Treat coma (See Coma and stupor), seizures (See Seizures), hypotension (See Hypotension), and arrhythmias (See QRS interval prolongation, Tachycardia, and Ventricular dysrhythmias) if they ...

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