Sulfonamides bacteriostatic action

Pharmacology Sulfonamides exert their bacteriostatic action by competitive antagonism of para-aminobenzoic acid (PABA), an essential component in folic acid synthesis. 

The use of pyrazole derivatives in medicine is undoubtedly the principal practical application. Certain alkylpyrazoles have shown quite significant bacteriostatic, bacteriocidal, and fungicidal actions.12-16 In this respect sulfonamides based on pyrazole are of particular interest, e. g. Orisul (1) which has a prolonged bacteriostatic action in vivo.17-20... 

Fig, 10.13 Effect, on bacteriostatic action, of variation in the pK of a series of sulfonamides. Organism E. coli. The substances on the left are the most highly ionized (as anions) at the pH of the test (pH 7, synthetic medium). (Bell and Roblin, 1942.)... 

Human pharmaceutical uses— PABA is sometimes used as a human pharmaceutical, not as a vitamin, in the following as an anti rickettsial to counteract the bacteriostatic action of sulfonamides and as a protective agent against sunburn. 

Unlike many drugs the mode of action of sulfonamides is well understood. They are bacteriostatic. Sulfanilamide mimics />-aminobenzoic acid (PABA), essential for Incorporation into enzymes regulating bacterial growth but nonessential for human growth. The bacteria mistake sulfur for... 

B. Humans cannot synthesize folic acid (A) diet is their main source. Sulfonamides selectively inhibit microbially synthesized folic acid. Incorporation (B) of PABA into microbial folic acid is competitively inhibited by sulfonamides. The TMP-SMX combination is synergistic because it acts at different steps in microbial folic acid synthesis. All sulfonamides are bacteriostatic. Inhibition of the transpeptidation reaction (C) involved in the synthesis of the bacterial cell wall is the basic mechanism of action of (3-lac-tam antibiotics Changes in DNA gyrases (D) and active efflux transport system are mechanisms for resistance to quinolones. Structural changes (E) in dihydropteroate synthetase and overproduction of PABA are mechanisms of resistance to the sulfonamides. 

The sulfonamides have a bacteriostatic rather than a bactericidal action. Many local anesthetics used in the eye are esters of para-aminobenzoic acid, and such drugs will interfere with the action of sulfonamides. Thus, to obtain the maximum effect from instillation of sulfonamide eye-drops, these drugs should not be used until the effect of the local anesthesia disappears. 

Sulfonamide antagonist. PABA has the ability to reverse the bacteriostatic effects of sulfonamides, thereby counteracting their action. This is an antimetabolite action, explainable on the basis of similarity of structures (see Fig. P-10). According to this theory, sulfonamides suppress bacterial... 

The effect produced by a sulfonamide on the microorganism s tetra-hydrofolate pools is a depletion contingent on slow attrition and dilution through cellular division. Eventually, the pool falls to a level that will no longer permit multiplication, and the organism passes into a resting phase. The sulfonamide is thus bacteriostatic in its action. 

Trimethoprim, however, is a competitive inhibitor of dihydrofolate reductase . The accumulation of dihydrofolate, through continuing biosynthesis and reoxidation of tetrahydrofolate, tends to increase the metabolite antimetabolite ratio and diminishes the effectiveness of the blockade. Conjoint application of a sulfonamide, however, removes the source of new dlhydrofolate and Improves the effectiveness of the inhibition. In practice the simultaneous use of the 2 inhibitors results in a 5-10-fold potentiation, broadening of the spectrum of action, a decreased liability to the development of resistance, and a conversion of bacteriostatic to bactericidal effects . 

A number of factors have been shown to influence the extent of this bacterial synthesis. The constituents of the diet proteins, fats, carbohydrates, and the different vitamins appear to play a significant part. The widespread use of bacteriostatic a nts (the sulfonamides), particularly in protracted therapy or prolonged prophylaxis, should obviously call for vigilance because of their action in suppressing synthesis of the various members of the B complex. 

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