Quinidine effects

Grant and Iliescu (23) preferred to evaluate quinine potency by an indirect method. They administered quinine in 0.6-g. doses to patients with auricular fibrillation. These subeffective but safer doses do not eliminate the arrhythmia but do cause a decrease in the auricular rate and an increase in ventricular rate. Again quinine proved to be inferior to quinidine quinine decreased the average auricular rate 86 beats/min. and increased the ventricular rate 15 comparable figures for quinidine are 161 and 45. Gold (2) reports that the maximum limit of reduction of auricular rate is twice as high for quinidine as for quinine quinine, even at 2.0-g. doses, produced only the slowing that quinidine effected at a 0.3-g. dose. 

Hardy BG, Schentag JJ. Lack of effect of cimetidine on the metabolism of quinidine effect on renal clearance. Inij Clin Pharmacol Ther Toxicol (1988) 26, 388-91. 

Although quinine is a favored antimalarial for parenteral adrninistration, it is nevertheless hazardous by this route. Quinidine (64), has been shown to be even more effective in combatting the disease (Table 8). However, it has undesirable cardiac side effects that reduce its suitabiHty as an antimalarial. 

The cardiovascular adverse effects associated with quinidine therapy are hypotension and tachycardia, both of which are related to its a-adrenoceptor blocking actions. The tachycardia may be a reflex adjustment to the fall in blood pressure or may also be a direct action of the dmg on sympathetic nerve terminals leading to an increased release of NE. Quinidine also produces ringing in the ears (cinchonism) (1,2). 

These changes have been experimentally demonstrated only for quinine and quinidine, but in view of the optical identity of the quinuclidine degradation products from the principal cinchona alkaloids, it may be assumed that in all of them the total dextrorotatory effect at C and C is made up of a dextrorotatory effect at C exceeding a laevorotatory effect at C. ... 

The effect of change in the spatial relations at C and C is not clear since, as explained above, there is doubt as to the relative activities of the components of the two pairs, quinine and quinidine, and cinchonidine and cinchonine, but epf-C -quinine and epi-C -quinidine are only slightly active or, according to Dirscherl and Thron, inactive. This result supports Neeman s view that for anti-malarial activity the direction of rotation must be the same at C and C but that does not explain the... 

Quinidine, the classical class IA drug, binds to the open state oftheNa+ channel, and prolongs the action potential by block of the delayed rectifier-. In higher concentrations, L-type Ca2+ channels are inhibited. Quinidine exerts antimuscarinic effects, thereby accelerating AV-nodal... 

Further class IA drugs include the open state blockers procainamide and disopyramide with electrophysiolog-ical effects similar to those of quinidine procainamide lacks the antimuscarinic and antiadrenergic effects. Characteristic side effects of procainamide are hypotension and immunological disorders. 

The risk of atrial flutter is a 2 1 transmission to the ventricles generating a high ventricular rate. The therapeutic goal is to reduce transmission to 3 1 or 4 1 by administration of either (3-adrenoceptor antagonists, Ca2+ channel blockers or amiodarone. Quinidine must not be used in this arrhythmia, since it accelerates AV-conduction due to its vagolytic effect. 

Amantadine is used cautiously in patients with seizure disorders, psychiatric problems, renal impairment, and cardiac disease. Amantadine is a Pregnancy Category B drug and is used cautiously during pregnancy and lactation. Concurrent use of antihistamines, phenothiazines, tricyclic antidepressants, disopyramide, and quinidine may increase the anticholinergic effects (dry mouth, blurred vision, constipation) of amantadine... 

The phenotiiiazines may decrease the effectiveness of tiie dopamine receptor agonists. When pramipexole is administered concurrently witii cimetidine, ranitidine, verapamil, and quinidine, there is an increased effect of pramipexole When ropinirole is administered with the estrogens, particularly estradiol, there may be an increased effect of ropinirole... 

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. 

Mr. Parker is at an outpatient clinic for a follow-up visit. He has been taking quinidine for several months for a cardiac arrhythmia. Analyze what assessments you would make on Mr. Parker to determine the effectiveness of quinidine therapy. Discuss what questions you would adz to determine the presence of any adverse reactions. 

Oral administration of bicarbonate may decrease the absorption of ketoconazole. Increased blood levels of quinidine, flecainide, or sympatiiomimetics may occur when these agents are administered with bicarbonate There is an increased risk of crystalluria when bicarbonate is administered with the fluoroquinolones. Fbssible decreased effects of lithium, methotrexate, chlorpropamide, salicylates, and tetracyclines may occur when these drag s are administered with sodium bicarbonate. Sodium bicarbonate is not administered within 2 hours of enteric-coated drugs the protective enteric coating may disintegrate before the drug reaches the intestine. 

Podrid PJ, Kowey PR, Frishman WF[, et al. Comparative cost-effectiveness analysis of quinidine, procainamide and mexiletine. Am J Cardiol 1991 68 1662-7. 

In symptomatic patients, medical therapy can be tailored either to control ventricular response or to restore sinus rhythm. Nondihydropyridine calcium antagonists (e.g., verapamil) are considered first-line drug therapy for decreasing ventricular response. Type I agents (e.g., procainamide, quinidine) are only occasionally effective in restoring sinus rhythm. DCC is ineffective, and /3-blockers are usually contraindicated because of coexisting severe pulmonary disease or uncompensated HF. 

Take drugs that have a direct irritant effect on the esophageal mucosa with plenty of liquid if they cannot be avoided (bisphosphonates, tetracyclines, quinidine, potassium chloride, iron salts, aspirin, nonsteroidal antiinflammatory drugs). 

The first attempt to effect the asymmetric cw-dihydroxylation of olefins with osmium tetroxide was reported in 1980 by Hentges and Sharpless.54 Taking into consideration that the rate of osmium(VI) ester formation can be accelerated by nucleophilic ligands such as pyridine, Hentges and Sharpless used 1-2-(2-menthyl)-pyridine as a chiral ligand. However, the diols obtained in this way were of low enantiomeric excess (3-18% ee only). The low ee was attributed to the instability of the osmium tetroxide chiral pyridine complexes. As a result, the naturally occurring cinchona alkaloids quinine and quinidine were derived to dihydroquinine and dihydroquinidine acetate and were selected as chiral... 

Wynberg3 has also effected stereoselective addition of (C2H5)2Zn to aryl aldehydes using cinchona alkaloids, particularly quinine and quinidine, which result in (R)- and (S)-alcohols in excess, respectively. The highest enantiomeric excess, 92% ee, was observed with o-ethoxybenzaldehyde catalyzed by quinine. 

Cervinka and co-workers have extensively investigated the asymmetric reduction of prochiral ketones with LAH modified with alkaloids and related amino alcohols. Most of this work has been reviewed in detail by Morrison and Mosher (1) and will not be discussed extensively here. Modification of LAH was effected with (-)-quinine (65), (- )-cinchonidine (66), (- )-ephedrine (67), (-)-A-ethyl-ephedrine (68), (-)- l-phenyl-2-dimethylaminoethanol (69), (+ )-quinidine (70), (+ )-cinchonine (71), and (+ )-pseudoephedrine (72). 

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