Protein bacterial synthesis, drugs acting

Sulfonamides were the first group of chemotherapeutic agents used for the prevention or treatment of bacterial infections in humans. Sulfonamides (e.g., sulfisoxazole) act by inhibiting bacterial synthesis of folic acid, a chemical required for synthesis of nucleic acid and protein. These drugs competitively inhibit the first step in the synthesis of folic acid—the conversion of para-aminobenzoic acid into dihydrofolic acid. Because humans absorb preformed folic acid from food, sulfonamide inhibition has only a minimal effect on hiunan cells. 

Inhibitors are substances that tend to decrease the rate of an enzyme-catalysed reaction. Although some act on the substrate, the discussion here will be restricted to those inhibitors which combine directly with the enzyme. Inhibitors have many uses, not only in the determination of the characteristics of enzymes, but also in aiding research into metabolic pathways where an inhibited enzyme will allow metabolites to build up so that they are present in detectable levels. Another important use is in the control of infection where drugs such as sulphanilamides competitively inhibit the synthesis of tetrahydrofolates which are vitamins essential to the growth of some bacteria. Many antibiotics are inhibitors of bacterial protein synthesis (e.g. tetracyclin) and cell-wall synthesis (e.g. penicillin). 

MECHANISM OF ACTION CUndamycin binds to the 50S subunit of bacterial ribosomes and suppresses protein synthesis. Although clindamycin, erythromycin, and chloramphenicol are not structurally related, they act at sites in close proximity (Figures 46-2 and 46-3), and ribosome binding by one of these drugs may inhibit the interaction of the others. MacroUde resistance due to ribosomal methylation also may produce resistance to clindamycin. Because clindamycin does not induce the methylase, there is cross-resistance only if the enzyme is produced constitutively. Clindamycin is not a substrate for macrolide efflux pumps thus, strains that are resistant to macroUdes by this mechanism are susceptible to clindamycin. 

C. Mechanisms of Action and Resistance Beta-lactam antibiotics are bactericidal drugs. They act to inhibit cell wall synthesis by the following steps (Figure 43 2) (1) binding of the drug to specific receptors (penicillin-binding proteins PBPs) located in the bacterial cytoplasmic membrane (2) inhibition of transpeptidase enzymes that act to cross-link linear peptido-glycan chains which form part of the cell wall and (3) activation of autolytic enzymes that cause lesions in the bacterial cell wall. 

Tetracyclines This very successful class of antibacterials act selectively on the bacterial ribosome inhibiting protein synthesis. They do not bind with mammalian ribosomes in the cytoplasm and, therefore, do not have a direct effect on the patient s metabolism. Like any drug, they are not free of potentially harmful side effects. They complex calcium and can interfere with development of the permanent teeth prior to their erupting through the gums As with the sulfonamides, this class... 

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