Quinidine antimalarial

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. 

It must not be forgotten that the concept of pure substance, referred to earlier, is very rigorous and must take into account, not just the constitution and relative configuration of a molecule, but also the absolute configuration of each chiral center that may present. For example, again in relation to quinine (i), quinidine (2) is also known and the only difference between the two molecules is the disposition in space of the groups bonded to C(8). Nevertheless 2 is a different molecule and shows no antimalarial activity. In addition, only one enantiomer of quinine (1), the laevorotatory, corresponds to the natural compound and manifests the specific physiological properties associated with this substance. 

Quinidine (6) and quinine (7) are diastereomeric quinoline alkaloids obtained from Cinchona spp. Quinidine (6) is included in many pharmacopeias for its antiarrhythmic effects.Quinine was the first antimalarial drug and served as an effective remedy for this deadly infectious disease in colonial times, making European settlement in many tropical and subtropical parts of the world possible.Owing to the development of resistance to synthetic antimalarials, quinine is still reverted to some extent for this... 

Antimalarial drugs are designed to prevent or treat malaria. Antimalarial drugs currently used for treatment for prophylaxis are mefloquine, primaquine, chloroquine, pyrimethamine, amodiaquin, quinine/quinidine, chloroguanide. 

VI.a.2.3. Quinine alkaloids. The quinine alkaloids include quinine and quinidine. Quinidine, the dextrorotatory diastereoisomer of quinine, is mainly used for the parenteral treatment of cardiac arrhythmias but it can be an alternative antimalarial in regions where Plasmodium falciparum is resistant to both chloroquine and antifolate-sulfonamide combinations. 

Mefloquine is effective in treating most falciparum malaria. The drug is not appropriate for treating individuals with severe or complicated malaria, since quinine, quinidine, and artemisinins are more rapidly active, and since drug resistance is less likely with those agents. The combination of artesunate plus mefloquine showed excellent antimalarial efficacy in regions of Southeast Asia with some resistance to mefloquine, and this regimen is now one of the combination therapies recommended by the WHO for the treatment of uncomplicated falciparum malaria (Table 52-4). Artesunate-mefloquine is the first-line therapy for uncomplicated malaria in a number of countries in Asia and South America. 

Clindamycin (see Chapter 44) is slowly active against erythrocytic schizonts and can be used after treatment courses of quinine, quinidine, or artesunate in those for whom doxycycline is not recommended, such as children and pregnant women. Azithromycin (see Chapter 44) also has antimalarial activity and is now under study as an alternative chemoprophylactic drug. Antimalarial activity of fluoroquinolones has been demonstrated, but efficacy for the therapy or chemoprophylaxis of malaria has been suboptimal. 

Quinidine, cinchonine, and cinchonidine also have antimalarial properties, but these alkaloids are not as effective as quinine. The cardiac effect makes quinidine unsuitable as an antimalarial. However, mixtures of total Cinchona alkaloids, even though low in quinine content, are acceptable antimalarial agents. This mixture, termed totaquine, has served as a substitute for quinine during shortages. Quinine-related alkaloids, especially quinidine, are also found in the bark of Remija pendunculata (Rubiaceae). 

Following the development of synthetic antimalarial agents, such as chloroquine and mefloquine, the use of Cinchona alkaloid quinine declined. However, with the emergence of chloroquine-resistant and multiple-drug-resistant strains of malarial parasites, its use has become firmly reestablished. Quinine is the drug of choice for severe chloroquine-resistant malaria due to Plasmodium falciparum. In the U.S., the related alkaloid quinidine is recommended because of its wide availability and use as an antiarrhythmic agent. In many clinics in the tropics, quinine is the only effective treatment for severe malaria unfortunately, decreasing sensitivity of P. falciparum to quinine has already been reported from Southeast Asia. 

During the last decades several drugs and compounds have been identified that to different degrees are able to overcome MDR so that the cells resemble sensitive cells in their chemosensitivity. These drugs mainly include catamphiphilic, membrane-active compounds and belong to various classes of drugs such as calcium channel blockers (verapamil), neuroleptics (flupentixol), anesthetics, antimalarial drugs (quinidine), antiarrhythmics (amiodarone), and many other compounds. Reviews were recently published [61, 157]. 

Quinidine, the dextrorotatory-isomer of quinine, has antimalarial activity, but is used mainly as a cardiac antiarrhythmic (see p. 500). 

Cinchona species (Rubiaceae) are sources of quinine and quinidine, containing a quinoline nucleus and derived through the extensive elaboration of strictosidine (Fig. 42). The intriguing history of the antimalarial quinine and its role in world politics over the past 350 years are legendary. It is frequently the only antimalarial drug to which patients are not resistant. Its widest use, however, is in the beverage industry in tonic water. Quinidine, an isomer of quinine, is used to treat cardiac arrythmias. 

It has tentatively been suggested that mefloquine can exacerbate psoriasis (as can other antimalarial drugs, such as quinidine, chloroquine, and proguanil) (38). 

Quinine and Quinidine. Quinine has been used for "fevers" in South America since the 1600s. The pure alkaloids quinine and cinchonine were isolated in 1820. The stereoisomer, quinidine, is a more potent antimalarial, but it... 

Common drug causes of lichenoid eruptions are antimalarials, beta-blockers, chlorpropamide, furosemide, gold, methyldopa, phenothiazines, quinidine, thiazides, and tolazamide. 

Drugs that can precipitate psoriasis are, among others, beta-blockers and lithium. Drugs that are reported to aggravate psoriasis are antimalarials, beta-blockers, lithium, NSAIDs, quinidine, and photosensitizing drugs. The effect and extent of these drug-induced psoriatic eruptions are dose-dependent. 

Quinine (2) is the major active principle of cinchona, which was isolated by Pelletier and Caventou in 1820 [16] however, its structure could only be established after 100 years [17]. The total synthesis of quinine was accomplished by Woodward and Doering [18] and others [19] but none of the synthetic methods are economical and, therefore, can not compete with the natural production of quinine the bark of the cinchona tree is still the only source of the drug. In addition to quinine (2), three more antimalarial components, quinidine (3), cinchonidine (4) and cinchonine (5) are present in the bark. 

Although quinidine is an effective antimalarial, on account of its higher cost and possibility to cause cardiac problems, it is used only when quinine is not available [62,123],... 

QUINIDINE Quinidine is one of the quinoline alkaloids in Cinchona bark. (See POl, Antimalaria-drugs). Thus, quinidine is an antiarrythmic drug, whereas its stereoisomer, quinine, is an antimalarial. In antiarryth-mically effective doses quinidine reduces the contraction capacity of the heart. The minute volume of the heart diminishes through its negative inotropic effect. Quinidine is used clinically for treatment of relapse into auricle fibrillation, and at extrasystohcs and paroxysmal tachycardia and ventricular tachycardia. 

Answer D. The symptoms described are those of cinchonism, which usually include tinnitus and, when more severe, CNS effects including hallucinations. Cinchonism is characteristic of quinidine and its optical isomer, the antimalarial drug quinine. Like most antiarrhythmic drugs, quinidine can cause cardiac arrhythmias heralded by the ECG changes described. 

Plants belonging to the genus Cinchona of the family Rubiaceae are not indigenous to Sri Lanka. Cinchona ledgeriana Moens. was introduced into Sri Lanka with the sole intention of exporting its bark (26,27) to extract the antimalarial quinoline alkaloid quinine (9) and its D-isomer, quinidine,... 

Cinchona alkaloids have been used since the sixteenth century to treat malaria. It is well established that quinine, quinidine, cinchonidine, cinchonine, and their dihydro derivatives exhibit similar antimalarial activity (50, 51). Quinine owes its favored position in malaria therapy to its earlier isolation. Its use is becoming increasingly important in treating infections caused by strains of Plasmodium falciparum which are resistant to all other antimalarial drugs (52). However, some of the... 

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