Antimalarial drugs pyrimethamine

Trimethoprim is a pyrimidine derivative (diaminopyrimidine) related to antimalarial drug pyrimethamine, which selectively inhibits bacterial dihydrofolate reductase, necessary for the conversion of dihydrofolate to tetrahydrofolic acid. Sulfonamides act by inhibiting the incorporation of PABA into dihydrofolate by bacteria. A combination of... 

The reverse situation exists for the antimalarial drug pyrimethamine." Trimethoprim does have some affinity for human folate reducta.se. and this i.s the cause of some of the toxic effects of the drug. 

The folate antagonists, pyrimethamine and sulfadiazine, inhibit the parasite s DHFR/TS synthase enzyme complex and the DHPS, respectively (Fig. 4) (see antimalarial drugs). To avoid deficiency of folic acid in patients treated with antifolate antagonists, folinic acid supplementation is recommended to reduce bone-marrow suppression. 

Rapidly dividing cells need an abundant supply of dTMP for DNA synthesis, and this creates a need for dihydrofolate reductase activity. Specific dihydrofolate reductase inhibitors have become especially useful as antibacterials, e.g. trimethoprim, and antimalarial drugs, e.g. pyrimethamine. 

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. 

Knowledge of local resistance patterns is important to determine the treatment regimen. There is increasing chloroquine and pyrimethamine-sulfado-xine (Fansidar) resistance in Africa and in some areas at the border of Thailand there is resistance for almost all antimalarial drugs including halofantrine, mefloquine and quinine. In these areas only the artemisinin derivatives (artemether, arteether, arte-sunate, dihydroartemisinin) are effective. 

A drug that is a weak base can be defined as a neutral molecule that can form a cation (a positively charged molecule) by combining with a proton. For example, pyrimethamine, an antimalarial drug, undergoes the following association-dissociation process ... 

Toxoplasmosis Lymph nodes many organs and tissues Pyrimethamine-sulfadiazine [see antimalarial drugs] other antibacterials [clindamycin] Trimethoprim-sulfamethoxazole another agent [azithromycin, clarithromycin, atovaquone, or dapsone]... 

A review of the use of mefloquine in pregnancy (47) did not suggest that mefloquine has a worse effect in pregnancy than other antimalarial drugs, such as chloroquine and pyrimethamine + sulfadoxine. 

Pyrimethamine is a folic acid antagonist that for many years has been used as an antimalarial drug [193-195], specially for chloroquine-resistant P. falciparum. Due to its synergistic activity, pyrimethamine also has been used, in combination with sulfadiazine or dapsone for the treatment or prophylaxis of cerebral toxoplasmosis or PCP in patients with AIDS [196]. 

In the course of 20th century, especially during World War II, a series of effective synthetic antimalarial drugs have been developed. Among them, chloroquine (2), mefloquine (3), and pyrimethamine (4), Fig. (1), became the drugs of choice in several programs and contributed to the almost complete eradication of malaria from Europe and North America. 

Quinine sulfate is the standard drug for oral treatment of acute attacks of malaria due to chloroquine-resistant P falciparum. It should be used in combination with one or more other antimalarial drugs such as doxycycUne, clindamycin, or pyrimethamine plus sulfadiazine. The answer is (E). 

Pyrimethamine in conjunction with sulfadoxine (25mg 500mg), under the brand name Fansidar (Roche), has been used successfully as an antimalarial drug for those subjects who display sensitization towards chloroquine therapy in malaria. 

Quinine was quantitated from serum, plasma, and red blood cell samples [794]. A silica column (A = 254 nm) and a 100/9/0.4 DCM/methanol/water (1 M perchloric acid) mobile phase were used. Elution was complete in < 1S min and detection limits of <250 ng/mL were reported. The,linear concentration range was 0.25-20 pg/mL. The k values for potential interferents were tabulated (e.g., quinidine, dihydroqui-nine, chloroquine, primaquine, dapsone, pyrimethamine). Further discrimination between other antimalarial drugs and quinine was achieved through the use of fluorescence detection (A = 350 nm, ex 418 nm, em). The authors noted that an increase in either the DCM or the perchloric acid concentration led to an increase in the k for quinine. 

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