Bacterial Cell Wall Synthesis and Function

Inhibition of Bacterial Cell Wall Synthesis and Function 

FIGURE 33-1 T Primary sites of antibacterial drug action on bacterial cells. See text for discussion. 

Consequently, drugs that cause inadequate production of peptidoglycans or other structural components within the cell wall may produce a selective bactericidal effect. Also, a limited number of antibacterial agents directly punch holes in the bacterial cell membrane, destroying the selective permeability and separation of internal from external environment, 

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Antibacterial Drugs That Inhibit Bacterial Cell Wall Synthesis and Function... 

This insertion is accomplished by an enzyme called transpeptidase. -Lactam antibiotics function as substrates for the transpeptidase, thereby establishing selective inhibition of bacterial cell wall synthesis. The structural similarity between -lactam antibiotics and the alanylalanine unit is remarkable as can be seen in Figure 6.8. 

Sterols comprise a very important class of compounds in plant and animal systems. Bacteria and other organisms utilize cholesterol or related sterols in the synthesis and maintenance of their cell walls. True sterols are present in cyanobacteria to only a very small degree they are largely replaced with a steroid-like class of triterpenoid known as the hopanoids. The carbon frameworks of sterols and bacterial hopanoids are synthesized in essentially the same manner as other terpenes, however, the cyclization reactions to yield their polycyclic skeletons are unique. A variety of sterols and hopanoids are found in cyanobacteria and they are believed to have important cellular functions in cell wall structure and function. " As discussed in Section 2.06.5, many of the hopanoids also possess a polyalcohol chain derived from a sugar. ... 

Mechanism of Action A second-generation cephalosporin that binds to bacterial cell membranes and inhibits cell wall synthesis. Therapeutic Effect Bactericidal. Pharmacokinetics Well absorbed from the GI tract. Protein binding 25%. Widely distributed. Primarily excreted unchanged in urine. Moderately removed by hemodialysis. Half-life 0.6-0.9 hr (increased in impaired renal function). 

Mecftantsm of Action A third-generation cephalosporin that binds to bacterial cell membranes. Therapeutic Effect Inhibits synthesis of bacterial cell wall. Bactericidal. Pharmacokinetics Widely distributed, including cerebrospinal fluid (CSF). Protein binding 82%-93%. Metabolized and excreted in kidney and urine. Removed by hemodialysis. Half-life 1.6-2.4 hr (half-life is increased with impaired renal function). 

Mechanism of Action A fixed-combination carbapenem. Imipenem penetrates the bacterial cell membrane and binds to penicillin-binding proteins, inhibiting cell wall synthesis. Cilastatin competitively inhibits the enzyme dehydropeptidase, preventing renal metabolism of imipenem. Therapeutic Effect Produces bacterial cell death. Pharmacokinetics Readily absorbed after IM administration. Protein binding 13%-21%. Widely distributed. Metabolized in the kidneys. Primarilyexcreted in urine. Removed by hemodialysis. Half-life 1 hr (increased in impaired renal function). 

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