Quinidine dosage

Serum quinidine levels can be reduced by phenytoin, phenobarbi-tal or primidone. Loss of arrhythmia control is possible if the quinidine dosage is not increased. 

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 If the anticonvulsants are withdrawn the quinidine dosage may need to be reduced to avoid quinidine toxicity.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. 

What is known about the interaction between quinidine and verapamil suggests that a reduction in the dosage of the quinidine may be needed to avoid toxicity. If the verapamil is given intravenously, use with caution and be alert for evidence of acute hypotension. Monitor the effects of concurrent use closely. There is actually a fixed dose preparation containing verapamil and quinidine (Cordichin) available in Germany, which is used for the management of atrial fibrillation. No interaction apparently occurs between quinidine and felodipine or nisoldipine. The situation with diltiazem is as yet uncertain but be alert for the need to reduce the quinidine dosage. 

When 4 patients were given 30 mL of kaolin-pectin Kaopectate), after a single 100-mg oral dose of quinidine, the maximal salivary quinidine concentration was reduced by 54% and the AUC by 58%, without any effect on absorption rate. There is a correlation between salivary and serum concentrations after a single (but not repeated) doses of quinidine. This is consistent with in vitro data showing quinidine is adsorbed onto kaolin, pectin, and kaolin-pectin. Documentation appears to be limited to these two studies, but be alert for the need to increase the quinidine dosage if kaolin-pectin is used concurrently. 

An elderly man with chronic atrial fibrillation, treated with quinidine sulfate 300 mg four times daily, was also given ketoconazole 200 mg daily, for candidal oesophagitis after antineoplastic therapy. Within 7 days his plasma quinidine levels had risen from a range of 1.4 to 2.7 mg/L up to 6.9 mg/L (normal range 2 to 5 mg/L) but he showed no evidence of toxicity. The elimination half-life of quinidine was found to be 25 hours (normal values in healthy subjects 6 to 7 hours). The quinidine dosage was reduced to 200 mg twice daily, but it needed to be increased to the former... 

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... 

Antacids also have clinically significant drug interactions with tetracycline, ferrous sulfate, isoniazid, quinidine, sul-fonylureas, and quinolone antibiotics. Antacid-drug interactions are influenced by antacid composition, dose, dosage schedule, and formulation. 

Test dose Administer a single 200 mg tablet of quinidine sulfate or 200 mg IM quinidine gluconate to determine whether the patient has an idiosyncratic reaction. Adjust the dosage to maintain plasma concentration between 2 to 6 mcg/mL. 

Atrial /7yffer- Administer quinidine after digitalization. Individualize dosage. 

Quinidine-induced syncope may occur with the usual dosage. 

Propafenone has some structural similarities to propranolol and possesses weak 3-blocking activity. Its spectrum of action is very similar to that of quinidine, but it does not prolong the action potential. Its sodium channel-blocking kinetics are similar to that of flecainide. Propafenone is metabolized in the liver, with an average half-life of 5-7 hours. The usual daily dosage of propafenone is 450-900 mg in three divided doses. The drug is used primarily for supraventricular arrhythmias. The most common adverse effects are a metallic taste and constipation arrhythmia exacerbation can also occur. 

Antiarrhythmic therapy carries with it a number of risks. In some cases, the risk of an adverse reaction is clearly related to high dosages or plasma concentrations. Examples include lidocaine-induced tremor or quinidine-induced cinchonism. In other cases, adverse reactions are unrelated to high plasma concentrations (eg, procainamide-induced agranulocytosis). For many serious adverse reactions to antiarrhythmic drugs, the combination of drug therapy and the underlying heart disease appears important. 

In overdose, 3 blockers block both and 32 adrenoceptors selectivity, if any, is lost at high dosage. The most toxic blocker is propranolol. As little as two to three times the therapeutic dose can cause serious toxicity. This may be because propranolol has additional properties At high doses it may cause sodium channel blocking effects similar to those seen with quinidine-like drugs, and it is lipophilic, allowing it to enter the CNS (see Chapter 10). 

The adverse effects of most serious concern relate to the cardiovascular system and seizure threshold. Actions on the adrenergic and cholinergic systems probably contribute to both hypotensive and direct cardiac effects, including alterations in heart rate, quinidine-like delays in conduction, and reduced myocardial contractility. The seizure threshold is lowered, increasing the frequency of epileptic seizures. All of these adverse effects can occur at therapeutic dosages in susceptible populations, such as elderly people, children, and people with cardiac problems or epilepsy, but are also a major cause of morbidity and mortality in accidental or intentional overdosage. Doses in excess of 500 mg can be seriously toxic, and death is fairly common when doses of 2 g or more are taken. 

Inhibitors of CYP450 2D6, such as paroxetine, fluoxetine, and quinidine, may increase plasma levels of duloxetine and require a dosage reduction of duloxetine... 

Drugs that meet one or more of the criteria given above and have been shown to exhibit significant differences in the bioavailability of marketed dosage forms include digoxin, quinidine, furosemide, nitrofurantoin, prednisone, chloramphenicol, theophylline, chlorpromazine, phenytoin, amitriptyline, and phenylbutazone. 

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