Quinidine toxicity

Quinidine Antacids and alkaline diet (alkaline urine) Quinidine toxicity... 

Karagueuzian, H., Kogan, B., Khan, S., Denton, T., Karplus, W., Man-del, W., and Diamond, G., Induction of cellular chaos during quinidine toxicity. Predictive power of nonlinear dynamic analysis for drug-induced proarrhythmia-A hypothesis, Journal of Electrocardiology, Vol. 24 Suppl, 1992, pp. 91-96. 

A) Quinidine toxicity caused by inhibition of quinidine metabohsm by the thiazide Direct effects of hydrochlorothiazide on the pacemaker of the heart Thiazide toxicity caused by the effects of quinidine on the kidneys Block of calcium current by the combination of quinidine plus thiazide Reduction of serum potassium caused by the diuretic action of hydrochlorothiazide An important therapeutic or toxic effect of loop diuretics is (A) Decreased blood volume Decreased heart rate Increased serum sodium Increased total body potassium Metabolic acidosis... 

Large rises in urinary pH due to the concurrent use of some antacids, diuretics or alkaline salts can cause quinidine retention, which could lead to quinidine toxicity, but there seems to be only one case on record of an adverse interaction (with an alumini-um/magnesium hydroxide antacid). Aluminium hydroxide alone appears not to interact. 

Established interactions of clinical importance although the documentation is limited. The concurrent use of phenytoin, primidone, phenobarbital or any other barbiturate need not be avoided, but be alert for the need to increase the quinidine dosage. If the anticonvulsants are withdrawn the quinidine dosage may need to be reduced to avoid quinidine toxicity. Where possible, quinidine serum levels should be monitored. 

A few patients have shown increased serum quinidine levels when stopping nifedipine, but in others no interaction has occurred and one study even suggests that quinidine serum levels may be slightly raised by nifedipine. Nifedipine levels may be modestly raised by quinidine. Verapamil reduces the clearance of quinidine and in one patient the serum quinidine levels doubled and quinidine toxicity developed. Acute hypotension has also been seen in three patients taking quinidine when they were given verapamil intravenously. Felodipine and nisoldipine appear not to interact, and the situation with diltiazem is unclear. 

Brandfonbrener M, Kronholm J, Jones HR. The effect of serum potassium concentration on quinidine toxicity. J Pharmacol Exp Ther 1966 154 250-254. 

All antiarrhythmic dra are used cautiously in patients with renal or hepatic disease. When renal or hepatic dysfunction is present, a dosage reduction may be necessary. All patients should be observed for renal and hepatic dysfunction. Quinidine and procainamide are used cautiously in patients with CHF. Disopyramide is used cautiously in patients with CHF, myasthenia gravis, or glaucoma, and in men with prostate enlargement. Bretylium is used cautiously in patients with digitalis toxicity because the initial release of norepinephrine with digitalis toxicity may exacerbate arrhythmias and symptoms of toxicity. Verapamil is used cautiously in patients with a history of serious ventricular arrhythmias or CHF. Electrolyte disturbances such as hypokalemia, hyperkalemia, or hypomagnesemia may alter the effects of the antiarrhythmic dru . Electrolytes are monitored frequently and imbalances corrected as soon as possible... 

When two antiarrhythmic dragp are administered concurrently the patient may experience additive effects and is at increased risk for drug toxicity. When quinidine and procainamide are administered with digitalis, tiie risk of digitalis toxicity is increased. Hiarmacologic effects of procainamide may be increased when procainamide is administered with quinidine When quinidine is administered with the barbiturates or cimetidine, quinidine serum levels may be increased. When quinidine is administered with verapamil, there is an increased risk of hypotensive effects. When quinidine is administered with disopyramide, there is an increased risk of increased disopyramide blood levels and/or decreased serum quinidine levels. 

Maintenance dose 0.125-0.25 mg PO/IV qd low potassium or magnesium levels potentiate toxicity reduce dose in renal failure toxicity indicated by nausea, headache, visual disturbances (yellow-green halos), ventricular arrhythmias. Quinidine, verapamil, and amiodarone elevate digoxin level. 

Qninidine exhibits all of the pharmacological properties of qninine, including antimalar-ial, fever-redncing, and other properties. Quinidine is used in varions forms of arrhythmia for preventing tachycardia and atrial fibrillation, and particularly for preventing ciliary fibrillation, paroxysmal snpraventricnlar tachycardia, extrasystole, and ventricular tachycardia. However, it is a toxic drug and is nsed relatively rarely. 

Quinidine is rapidly absorbed from the Gl tract. Maximum effects of quinidine gluconate occur 30 to 90 minutes after IM administration onset is more rapid after IV administration. Activity persists for at least 6 to 8 hours. The average therapeutic serum levels are reported to be 2 to 7 mcg/mL. Toxic reactions may occur at levels from 5 to 8 mcg/mL or more. Quinidine is 80% to 90% bound to plasma proteins the unbound fraction may be significantly increased in patients with hepatic insufficiency. 

Cardiac toxicity Moxifloxacin and gatifloxacin have been shown to prolong the QT interval of the electrocardiogram in some patients. Avoid in patients with known prolongation of the QT interval, patients with uncorrected hypokalemia, and patients receiving class lA (eg, quinidine, procainamide) or class III (eg, amiodarone, sotalol) antiarrhythmic agents. 

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