What are the features of quinine (antimalarial medication) toxicity?

From the Guidelines

Quinine toxicity is characterized by cinchonism, which includes symptoms such as tinnitus, vertigo, headache, and acute hearing loss, as well as hypoglycemia 1.

Features of Quinine Toxicity

• Cinchonism: a condition caused by an overdose of quinine, characterized by symptoms such as:
  • Tinnitus: ringing or buzzing in the ears
  • Vertigo: dizziness or loss of balance
  • Headache: pain in the head
  • Acute hearing loss: sudden loss of hearing
• Hypoglycemia: low blood sugar levels, which can be exacerbated by quinine-induced hyperinsulinemia 1

Management of Quinine Toxicity

It is essential to monitor patients taking quinine for signs of toxicity and to adjust the dosage or discontinue treatment if necessary. In cases of severe quinine toxicity, treatment may involve:

• Cardiac monitoring: to monitor for cardiac complications such as QT interval prolongation and ventricular arrhythmia 1
• Intravenous dextrose: to treat hypoglycemia 1
• Slowing infusion rates: to prevent further toxicity in patients receiving quinidine gluconate 1

From the FDA Drug Label

Quinine overdose can be associated with serious complications, including visual impairment, hypoglycemia, cardiac arrhythmias, and death. Visual impairment can range from blurred vision and defective color perception, to visual field constriction and permanent blindness. Cinchonism occurs in virtually all patients with quinine overdose Symptoms range from headache, nausea, vomiting, abdominal pain, diarrhea, tinnitus, vertigo, hearing impairment, sweating, flushing, and blurred vision, to deafness, blindness, serious cardiac arrhythmias, hypotension, and circulatory collapse Central nervous system toxicity (drowsiness, disturbances of consciousness, ataxia, convulsions, respiratory depression, and coma) has also been reported with quinine overdose, as well as pulmonary edema and adult respiratory distress syndrome Most toxic reactions are dose-related; however, some reactions may be idiosyncratic because of the variable sensitivity of patients to the toxic effects of quinine. A lethal dose of quinine has not been clearly defined, but fatalities have been reported after the ingestion of 2 to 8 grams in adults. Quinine, like quinidine, has Class I antiarrhythmic properties The cardiotoxicity of quinine is due to its negative inotropic action, and to its effect on cardiac conduction, resulting in decreased rates of depolarization and conduction, and increased action potential and effective refractory period ECG changes observed with quinine overdose include sinus tachycardia, PR prolongation, T wave inversion, bundle branch block, an increased QT interval, and a widening of the QRS complex. Quinine's alpha-blocking properties may result in hypotension and further exacerbate myocardial depression by decreasing coronary perfusion Quinine overdose has been also associated with hypotension, cardiogenic shock, and circulatory collapse, ventricular arrhythmias, including ventricular tachycardia, ventricular fibrillation, idioventricular rhythm, and torsades de pointes, as well as bradycardia, and atrioventricular block

The features of quinine toxicity include:

• Visual impairment: blurred vision, defective color perception, visual field constriction, permanent blindness
• Cinchonism: headache, nausea, vomiting, abdominal pain, diarrhea, tinnitus, vertigo, hearing impairment, sweating, flushing
• Cardiac arrhythmias: sinus tachycardia, PR prolongation, T wave inversion, bundle branch block, increased QT interval, widening of the QRS complex
• Central nervous system toxicity: drowsiness, disturbances of consciousness, ataxia, convulsions, respiratory depression, coma
• Hypotension and cardiogenic shock
• Ventricular arrhythmias: ventricular tachycardia, ventricular fibrillation, idioventricular rhythm, torsades de pointes
• Bradycardia and atrioventricular block
• Pulmonary edema and adult respiratory distress syndrome 2 2

From the Research

Features of Quinine Toxicity

The features of quinine toxicity can be summarized as follows:

• Cardiovascular toxicity, including cardiogenic shock, conduction disturbances, and ventricular arrhythmias 3
• Neurological toxicity, including obnubilation, coma, convulsions, and respiratory depression 3
• Ocular toxicity, including blindness 3
• Hypokalemia, which is consistently present in severe quinine poisoning 3
• Cinchonism, which includes symptoms such as tinnitus, hearing loss, and vertigo 4
• Hypoglycemia, which is a frequent complication of quinine therapy 4
• Cardiotoxicity, which can lead to fatal bradyarrhythmia or broad QRS tachycardia 4
• Neurophysiological effects, including depolarization of the resting membrane potential, attenuation of rebound spikes, and broadening of action potentials in dopaminergic neurons 5

Risk Factors for Quinine Toxicity

Certain risk factors can increase the likelihood of quinine toxicity, including:

• Impaired hepatic or renal function 4
• Prolonged QTc interval 4
• High doses of quinine, particularly when administered parenterally 4, 6
• Combination with other medications that can increase the risk of toxicity 7

Clinical Presentation of Quinine Toxicity

The clinical presentation of quinine toxicity can vary depending on the severity of the overdose and the individual patient's response. Common symptoms include:

• Cardiovascular instability, including hypotension and arrhythmias 3, 4
• Neurological symptoms, including confusion, seizures, and coma 3, 4
• Gastrointestinal symptoms, including nausea and vomiting 4
• Ocular symptoms, including blurred vision and blindness 3