Quinidines

Quinidine overdose should be treated with symptomatic and supportive therapy. Quinidine should be used with caution when coadministering with calcium channel blockers, diuretics, beta-blockers, antibacterials, antifungals, and antiarrhythmics.97 

Allergic reaction due to streptokinase overdose should be treated with corticosteroids and histamines. Severe hemorrhage requires discontinuation of streptokinase. Packed red blood cells are preferable for blood-replacement therapy, and volume expansion is advisable. Streptokinase may be used with caution with heparin, allopurinol, sex hormones, sulfonamides, tetracyclines, and dextran. 

Treatment for verapamil overdose includes gastric lavage, administration of activated charcoal, symptomatic and supportive cardiovascular treatment, and calcium gluconate injection. Verapamil should be used carefully with calcium salts, beta-blockers, antineoplastics, antiepileptics, antibacterials, anxiolytics, and anti-arrhythmics. 

Hypersensitivity reactions associated with quinidine are rare, but some of the reported cases have been extensively investigated. Practically all the immunologically induced adverse responses seem to be confined to the formed elements of the blood or to the skin. 

This study was written when the author was employed by the British Industrial Biological Research Association. His current affiliation can be found in the List of Contributors. 

Thrombocytopenia is a well-recognized hypersensitivity reaction, inducible by quinidine, but only about 50 cases have been reported (Robinson 1978). Hemolytic anemia is even more rare one well-documented case was reported by Freedman et al. (1956) and one case of agranulocytosis with marrow depression was reported by Barzel (1967). 

Cutaneous reactions are uncommon with quinidine they are more commonly associated with the optical isomer, quinine. Drug fever either occuring alone or in combination with other symptoms is a more frequent manifestation of hypersensitivity than the cutaneous signs (Sturnick 1942), but even quinidine fever is very unusual (Abrams 1973). 

White crystalline solid bitter taste mp 174°C (345.2°F) blue fluorescence slightly solnble in water, soluble in alcohols and chloroform. 

Quinidine is more potent than quinine in its action on the cardiovascular system. Overdoses may cause loweriug of blood pressure. Gastric effects are lower thau quiuiue. Toxicity is lower relative to quiuiue subcutaueous lethal dose in mice is 400 mg/kg against 200 mg/kg for quinine. 

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Na+ K+ Ga + TTX, DDT, veratridine, scorpion toxins, procaine, Hdocaine quinidine, tolbutamide, diazoxide, glyburide, minoxidil nifedipine, diltiazem, verapamil, moUusc and spider toxins ... 

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. 

QuinidJne. Quinidine, an alkaloid obtained from cinchona bark (Sinchona sp.), is the dextrorotatory stereoisomer of quinine [130-95-0] (see Alkaloids). The first use of quinidine for the treatment of atrial fibrillation was reported in 1918 (12). The sulfate, gluconate, and polygalacturonate salts are used in clinical practice. The dmg is given mainly by the oral (po) route, rarely by the intravenous (iv) route of adniinistration. It is the most frequentiy prescribed po antiarrhythmic agent in the United States. The clinical uses of quinidine include suppression of atrial and ventricular extrasystoles and serious ventricular arrhythmias (1 3). 

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). 

The disadvantage in war periods of relying on a single source of supply for an essential commodity became evident when Java was invaded by the Japanese in March 1942, the world being thereby deprived of about 90 per cent, of its customary supply of cinchona bark. Quinine was ther still considered an indispensable drug for the treatment of malaria an<3 its use had to be restricted to that purpose stocks of quinidine wew similarly reserved for use in cardiac disease, In efforts to deal with th<... 

The cinchona alkaloids of practical importance are quinine, quinidine, cinchonine and cinchonidine, but, in addition, over twenty others have been isolated from cinchona and cuprea species. Their names and formulae are as follows ... 

Quinine, quinidine, quinicine, epfquinine, e fquinidine, A-quinine.. ... 

For the separate determination of the four principal components in the total alkaloids, the method in general use is based on the isolation of quinine and cinchonidine as d-tartrates, of cinchonine as the base in virtue of its sparing solubility in ether, and of quinidine as the hydriodide. Types of this method have been described by Chick, and special modifications designed for use in the analysis of totaquina are given in the British Pharmacopoeia 1932 and in a special report by the Malaria Commission of the League of Nations. Goodson and Henry have critically examined this process and shown that, with care, it gives satisfactory... 

Quinidine is alkaline in solution and behaves as a diacidic base forming two series of salts. The neutral sulphate, Bj. H2SO4.2HjO, crystallises from hot water in colourless prisms, soluble in water (1 in 98 to 100 at 15°, or 1 in 7 at 100°), more so in alcohol or chloroform, and scarcely in ether. It is dextrorotatory, [a]D +184-17° (CHCI3). The acid sulphate, B. H2SO4.4H2O, forms hair-like, colourless needles, soluble in 8-7 parts of water at 10° + 247-8° (c = M/10, HjO) or + 256-4° (c = M/40,... 

Cmchonine, C19H22ON2. This alkaloid is usually present in cinchona and cuprea barks. One of the best sources is Cinchona micrantha bark. It occurs in the crude quinine sulphate mother liquors. The mixed alkaloids recovered from these may be extracted with ether to remove quinidine and cinchonidine and the insoluble residue boiled with successive small quantities of alcohol, from which cinchonine crystallises on cooling. The crude alkaloid is neutralised with dilute sulphuric acid and the sulphate recrystallised from boiling water. Cinchonine so prepared contains quinidine, from which it may be freed by crystallisation from boiling alcohol until it ceases to exhibit fluorescence in dilute sulphuric acid. It will then still contain 10 to 15 per cent, of dihydrocinchonine, which may be removed by reprecipitation as the cuprichloride, B. 2HC1. CuClj, or by the simpler mercuric acetate process of Thron and Dirscherl. ... 

The ethereal solution of crude quinidine and cinchonidine, obtained as described under cinchonine, is shaken with dilute hydrochloric acid, the excess acid neutralised with ammonia and sodium potassium tartrate added. The base is recovered from the precipitated tartrate by dissolving the latter in dilute acid and pouring the filtered solution in a thin stream, slowly and with constant stirring, into excess of ammonia solution. The crude alkaloid is converted into the neutral sulphate, and this recrystallised... 

Detection. Cinchonidine is distinguished from quinine and quinidine by not being fluorescent in dilute sulphuric acid, and by not giving the thalleioquin reaction and from cinchonine in being laevorotatory and more soluble in ether, and in the sparing solubility of its tartrate. 

Cinchotine (Hydrocinohonine, more correctly dihydrocinchonine, Cinchonifine, >fs-Cinchonine), C19H24ON2. This alkaloid occurs in commercial cinchonine to the extent of about 14 per cent. and may be prepared from this source by the mercuric acetate process, or more conveniently by the hydrogenation of commercial cinchonine previously freed from quinidine. ... 

The isomeride quiienidine, similarly produced by the oxidation of quinidine, crystallises in prisms, m.p. 246°, [a]f ° -(- 258° (A -H jS04), and, like quitenine, gives quininic and cincholoiponic acids by further oxidation. 

These results indicate that quinine and quinidine differ in structure from cinchonine and cinehonidine in containing a methoxyl group in position 6 in a quinoline nucleus. The identity of the other oxidation products, meroquinenine, cincboloiponic and loiponic acids, in all foiu" cases indicates that the second half of the molecule has the same structure in all four alkaloids. Further, this second half must be joined to the quinoline nucleus at position 4 by a group capable of conversion into carboxyl. 

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