Antibacterial drugs:

Sulfonamides or Sulfa drugs

These are also structural analogues , those molecules which are structurally similar tom metabolic intermediates. These compete with metabolites in metabolic processes because of their similarity, but are just different enough so that they cannot function normally in cellular metabolism. The first antimetabolites to be used successfully were the sulphonamides or sulfa drugs which are structurally related to sulphanilamide, an analogue of p-aminobenzoic acid, which is used in the synthesis of the cofactor folic acid. When this enters a bacterial cell, it competes with PABA for the active site of an enzyme involved in folic acid synthesis, and the folate concentration decreases. The decline in folic acid is detrimental to bacteria because folic acid is essential to the synthesis of purines and pyramidines, the bases used in the construction of DNA, RNA and other important cell constituents. This leads to cessation of bacterial growth and death of the pathogen. Sulfonamides are selectively toxic for many pathogens because these bacteria manufacture their own folic acid and cannot effectively take up the cofactor. In contrast, humans cannot synthesize folic acid and must obtain it in the diet; therefore sulphonamides will not affect the host.

Quinolones:

Are synthetic drugs that contain the 4-quinolone ring. These are effective when administered orally and the first quinolone, nalidixic acid was synthesized in 1962. Other quinolones belonging to fluoroquinolones has been produced (ciprofloxacin, norfloxacin and ofloxacin). They act by inhibiting the bacterial DNA gyrase or topoisomerase II, probably by binding to the DNA gyrase complex. This enzyme introduces negative twists in DNA and helps separate its strands. DNA gyrase inhibition disrupts DNA replication and repair, transcription, bacterial chromosome separation during division, and other cell processes involving DNA. These drugs are broad-spectrum and are highly effective against enteric bacteria such as E.coli and Klebsiella pneumonia . Other gram-negative pathogens like Haemophilus, Neisseria, and Pseudomonas aeruginosa are also susceptible. Gram negative bacteria include Staphylococcus aureus, Streptococcus pyogenes and Mycobacterium tuberculosis. Currently they are mostly used in treating urinary tract infections, sexually transmitted diseases caused by Neisseria and Chlamydia, gastrointestinal infections, respiratory tract infections, skin infections and osteomyelitis.

Penicillins:

Penicillin G or benzylpenicillin was the first antibiotic to be used in medicine. Most penicillins are derivatives of 6-aminopenicillanic acid and differ from one another only with respect to the side chain attached to its amino group. The most crucial feature of the molecule is the β -lactam ring, which appears to be essential for activity. Penicillinase, the enzyme synthesized by many penicillin resistant bacteria, destroys penicillin activity by hydrolyzing a bond in this ring. Their structures do resemble that of the terminal D-alanyl D-analine found on the peptide side chain of the peptidoglycan subunit. It has been proposed that penicillins inhibit the enzyme catalyzing the transpeptidation reaction because of their structural similarity, which would block the synthesis of a complete, fully cross-linked peptidoglycan and lead to osmotic lysis. An increasing number of bacteria are penicillin resistant. Penicillinase –resistant penicillins such as methicillin, nafcillin, and oxacillin are frequently employed against these bacterial pathogens. Penicillin G is highly active against most gram-positive bacteria, low against gram negative; but destroyed by acid and penicillinase. Penicillin V is more acid resistant than penicillin G. Ampicillin is against gram positive ad gram negative bacteria, but is acid stable. Carbenicillin is active against gram-negative bacteria like Pseudomonas and Proteus, is acid stable, not well absorbed b small intestine. Although penicillins are the least toxic of the antibiotics, about 1 to 5% of the adults in the USA are allergic to them. Occasionally a person will die of a violent allergic response; therefore patients should be questioned about penicillin allergies before treatment is begun. Cephalosporins are similar to penicillins and are given to people with penicillin allergy.