**10.1 Sulfadoxine and pyrimethamine**

A sulfonamide antibacterial drug and a pyrimidinediamine similar to trimethoprim are used in this combination. Sulfonamides can be used in conjunction with pyrimethamine in a variety of ways. A sulfonamide with similar pharmacokinetic properties to the dihydrofolate reductase inhibitor is usually used (**Figure 14**).

Sulfadoxine, a sulfonamide with a structure identical to p-aminobenzoic acid (PABA), inhibits the parasite's ability to synthesise folic acid, whereas pyrimethamine, a pyrimidinediamine, prevents folic acid from being reduced to its active tetrahydrofolate coenzyme type. Sulfonamides avoid the production of dihydropteroic acid by preventing the incorporation of p-aminobenzoic acid (PABA). Since humans do not need to synthesise folic acid, sulfonamides have excellent selective toxicity. Nonetheless, sulfadoxine has been linked to serious to fatal cases of erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, and serum sickness syndromes. Pyrimethamine, first formulated in the 1950s, prevents the conversion of folic acid and dihydrofolic acid to the active tetrahydrofolate coenzyme form, which is required for amino acid and nucleic acid synthesis [91]. This combination is recommended for the prevention and treatment of *P. falciparum* chloroquine resistance and can be used in conjunction with quinine. Despite the fact that the combination is only suggested for *P. falciparum*, it is successful against all asexual erythocytic forms. It does not have any impact on the sexual gametocyte form [92].
