Sulfadoxin

The success of quinine inspired the search for other antimalarials. The greatest impetus for the development of synthetic dmgs came this century when the two World Wars intermpted the supply of cinchona bark to the combatants. A stmcturally related 4-quinolinemethanol is mefloquine (65, Lariam [51773-92-3]) which now serves as an effective alternative agent for chloroquine-resistant P. falciparum. This is a potent substance that requires less than one-tenth the dose of quinine to effect cures. There are some untoward side effects associated with this dmg such as gastrointestinal upset and dizziness, but they tend to be transient. Mefloquine is not recommended for use by those using beta-blockers, those whose job requires fine coordination and spatial discrimination, or those with a history of epilepsy or psychiatric disorders. A combination of mefloquine with Fansidar (a mixture of pyrimethamine and sulfadoxine) is known as Fansimef but its use is not recommended. Resistance to mefloquine has been reported even though the compound has not been in wide use. 

The first are competitors of PABA (p-aminobenzoic acid) and thus intermpt host de novo formation of the tetrahydrofoUc acid required for nucleic acid synthesis. Examples of dmgs that fall into this group are the sulfones and sulfonamides. The most weU-known of the sulfones is dapsone (70, 4,4 -diaminodiphenyl sulfone, DDS), whose toxicity has discouraged its use. Production of foHc acid, which consists of PABA, a pteridine unit, and glutamate, is disturbed by the substitution of a sulfonamide (stmcturally similar to PABA). The antimalarial sulfonamides include sulfadoxine (71, Fanasd [2447-57-6]) sulfadiazine (25), and sulfalene (72, sulfamethoxypyrazine [152-47-6] Kelfizina). Compounds of this group are rapidly absorbed but are cleared slowly. 

ACTs are currently recommended artemether-lume-fantrine, artesunate + amodiaquine, artesunate + mefloquine, artesunate + sulfadoxine-pyrimethamine [1, 5]. In areas with amodiaquine and sulfadoxine-pyrimethamine resistance exceeding 20%, i.e., SE Asia, artesunate + mefloquine or artemether-lumefantrine should be used [1,5]. 

CjHgClNOsS 121-60-8) see Sulfacitine Sulfadiazine Sulfadicramide Sulfadimethoxine Sulfadoxine ... 

C21H27CIFN7O2 32566-14-6) see Flurazepam 4-amino-2-chloro-5-fluoropyrimidine (C4H2CIFN3 155-10-2) see Flucytosine 4-amino-6-chloro-S-methoxypyrimidine (CjHdClNjO 5018-41-7) see Sulfadoxine... 

CH3NO 75-12-7) see Allopurinol Chlorothiazide Cimetidine Fludarabinc phosphate Fluspirilene Heptaminol Primidone Protriptyline Pyridoxine Razoxane Sulfadoxine Theophylline... 

CijHijOj 229J5-4/-7) see Misoprostol metboxyoxobutanedioic acid dimethyl ester (C7H oO 36797-93-0) see Sulfadoxine... 

Different antimalarials selectively kill the parasite s different developmental forms. The mechanism of action is known for some of them pyrimethamine and dapsone inhibit dihydrofolate reductase (p. 273), as does chlorguanide (proguanil) via its active metabolite. The sulfonamide sulfadoxine inhibits synthesis of dihydrofolic acid (p. 272). Chlo-roquine and quinine accumulate within the acidic vacuoles of blood schizonts and inhibit polymerization of heme, the latter substance being toxic for the schizonts. 

Plasmodium (P.) falciparum, responsible for the most dangerous form of malaria, is particularly prone to develop drug resistance. The incidence of resistant strains rises with increasing frequency of drug use. Resistance has been reported for chloroquine and also for the combination pyrimethamine/ sulfadoxine. 

Antimalarial therapy employs the same agents and is based on the same principles. The blood-schizonticidal halofantrine is reserved for therapy only. The pyrimethamine-sulfadoxine combination may be used for initial selftreatment. 

Sulfalene is also a very long-lasting bacteriostatic sulfanilamide with a broad spectrum of antimicrobial activity. It is used for the same indications as sulfadoxine. Its half-life is about 150-200 h. This drug binds to proteins in the plasma to a lesser degree than other sulfanilamides, which ensures its high concentration in the blood in a free form. Therefore, only one dose of sulfalene needs to be taken one time per week. Synonyms of this drug are celfizin, sulfamethopyrazine, sulfamethoxypyrazine, and others. 

Malaria (doxycycline only) Prophylaxis of malaria due to Plasmodium falciparum in short-term travelers (less than 4 months) to areas with chloroquine and/or pyrimethamine-sulfadoxine resistant strains. 

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