Quinidine drug reaction

Observational studies In a retrospective study of oral quinidine for termination of atrial fibrillation in 501 consecutive patients (mean age 66 years, 32% women), quinidine 200-400 mg was given every 6 hours until cardioversion or for a maximum of 48 hours [87 ]. Quinidine did not have to be withdrawn because of adverse drug reactions and there was no significant QT interval prolongation and no life-threatening ventricular dysrhythmias. The mean total dose of quinidine was 617 mg and 92% of the patients received verapamil or a beta-blocker to slow the ventricular rate to below 100/minute. Cardioversion was successful in 84%. All adverse drug... 

The answer is a. (Katzung, p 162.) Many drugs can cause an immunohemolytic anemia. Methyldopa may cause a positive Coombs test in as many as 20% of patients, along with hemolytic anemia. Other drugs with similar actions on red blood cells are penicillins, quinidine, procainamide, and sulfonamides. These form a stable or unstable hapten on the red cell surface, which induces an immune reaction I immunoglobulin G (IgG) antibodies] and leads to dissolution of the membrane. 

The answer is b. (Hardmanr p 906.) Cimetidine reversibly inhibits cytochrome P450. This is important in phase I bio transformation reactions and inhibits the metabolism of such drugs as warfarin, phenytoin, propranolol, metoprolol, quinidine, and theophylline. None of the other enzymes are significantly affected. 

Hypersensitivity or idiosyncrasy to quinidine or other cinchona derivatives manifested by thrombocytopenia, skin eruption or febrile reactions myasthenia gravis history of thrombocytopenic purpura associated with quinidine administration digitalis intoxication manifested by arrhythmias or AV conduction disorders complete heart block left bundle branch block or other severe intraventricular conduction defects exhibiting marked QRS widening or bizarre complexes complete AV block with an AV nodal or idioventricular pacemaker aberrant ectopic impulses and abnormal rhythms due to escape mechanisms history of drug-induced torsade de pointes history of long QT syndrome. 

Hypersensitivity reactions Asthma, muscle weakness, and infection with fever prior to quinidine administration may mask hypersensitivity reactions to the drug. Pregnancy Category C. 

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. 

Other reactions include pruritus, which may be intolerable and is common in Africans, headaches, gastrointestinal disturbance, precipitation of acute intermittent porphyria in susceptible individuals, mental disturbances and interference with cardiac rhythm, the latter especially if the drug is given intravenously in high dose (it has a quinidine-like action). Long-term use is associated with reversible bleaching of the hair and pigmentation of the hard palate. 

Hypersusceptibihty reactions to quinidine include granulomatous hepatitis. In one retrospective series of 487 patients, 32 had evidence of hypersusceptibility, 10 of whom had hepatotoxicity (44). In another series of 1500 patients, quinidine-induced hepatitis was identified in 33 (2.2%) (45) these represented one-third of all cases of drug-induced hepatitis in those patients. In all cases the liver damage resolved on withdrawal. 

Cohen IS, lick H, Cohen SI. Adverse reactions to quinidine in hospitalized patients findings based on data from the Boston Collaborative Drug Surveillance Program. Prog Cardiovasc Dis 1977 20(2) 151-63. 

Photoallergic reactions may occur as a result of exposure to systemically administered drugs such as griseofulvin, NSAIDs, phenothiazines, quinidine, sulfonamides, sulfonylureas, and thiazide diuretics as well as to external agents such as para-aminobenzoic acid (found in sunscreens), bithionol (used in soaps and cosmetics), paraphenylenediamine, and others. 

Cells commonly affected hy these types of reactions include erythrocytes, leukocytes, and platelets, resulting in hemolytic anemia, agranulocytosis, or thrombocytopenia, respectively. This process may be initiated by drugs such as penicillin, quinidine, quinine, phenacetin, cephalosporins, and sulfonamides. 

Noncardiac Diarrhea is the most common adverse effect during quinidine therapy, occurring in 30-50% of patients, usually within the first several days of quinidine therapy but sometimes later. Diarrhea-induced hypokalemia may potentiate the risk of torsades de pointes due to quinidine. A number of immunological reactions can occur during quinidine therapy. The most common is thrombocytopenia, which can be severe but resolves rapidly with drug discontinuation. Hepatitis, bone marrow depression, and lupus syndrome occur rarely. None of these effects is related to elevated plasma quinidine concentrations. Quinidine also can produce cinchonism, a syndrome that includes headache and tinnitus. In contrast to other adverse responses to quinidine therapy cinchonism usually is related to elevated plasma quinidine concentrations and can be managed by dose reduction. 

Type II, or cytolytic, reactions are mediated by both IgG and IgM antibodies and usually are attributed to their ability to activate the complement systerrr The major target tissues for cytolytic reactions are the cells in the circulatory system. Examples of type II allergic responses include penicillin-inhemolytic anemia, methyldopa-indMced autoimmune hemolytic anemia, quinidine-induced thrombocytopenic purpura, and sulfonamide-induced granulocytopenia. These autoimmune reactions to drugs usually subside within several months after removal of the offending agent. 

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