Cell wall synthesis inhibitors
Members the group: Beta-lactam antibiotics, vancomycin, bacitracine, and cycloserine
Beta-lactam antibiotics: Penicillins, cephalosporins, carbapenems, and monobactams are members of the family. All members of the family have a beta-lactam ring and a carboxyl group resulting in similarities in the pharmacokinetics and mechanism of action of the group members. They are water-soluble, elimination is primary renal and organic anion transport system is used.
Penicillins
Penicillins have similar structure, pharmacological and toxicological properties. The prototype of penicillins is penicillin G and is naturally derived from a genus of moulds called penicillium.
Classification: Penicillins can be classified into three groups: Natural Penicillins, Antistaphylococcal penicillins, and Extended-spectrum penicillins.
Mechanism of Action: Penicillins inhibit bacterial growth by interfering with a specific step in bacterial cell wall synthesis (block the transpeptidation reaction). Sensitive pencillins are inactivatived by betalactamase enzymes.
Pharmacokinetics: Penicillin G is unstable in acid media, hence destroyed by gastric juice. Ampicillin, amoxicillin, and dicloxacillin are acid-stable and relatively well absorbed after oral adminstraion. Oral penicillins should be given 1-2 hours before or after meals to minimize binding to food proteins and acid inactivation (except ampicilin). The absorption of most penicillin is complete and rapid after IM administration. The kidneys rapidly excrete penicillin. Renal excretion is by glomerular filtration (10%) and by tubular secretion (90%). Blood levels of all penicillins can be raised by simultaneous administration of probenecid orally, which impairs tubular secretion of weak acids.
Clinical Uses
Natural Penicillins: Penicillin G and penicillin V are natural penicillins. Penicillin G is the drug of choice for infections caused by streptococci, meningococci, enterococci, penicillin-susceptible pneumococci, non-beta-lactamase-producing staphylococci, Treponema pallidum and many other spirochetes, Bacillus anthracis, Clostridium species, Actinomyces, and other gram- positive rods and non-beta-lactamase-producing gram-negative anaerobic organisms. Penicillin V is acid stable but it is less potent than penicillin G.
Antistaphylococcal Penicillins: [Methicillin, Nafcillin, isoxazolyl penicillins (Oxacillin, cloxacillin, and dicloxacillin)]. The only indication is infections caused by beta-lactamase-producing staphylococci. Oral isoxazolyl penicillin is suitable for treatment of mild localized staphylococcal infections, for serious systemic staphylococcal infections, oxacillin or nafcillin, is given by intermittent intravenous infusion.
Extended Spectrum Penicillins: Aminopenicillins (ampicillin, amoxicillin), Carboxypenicillins (Carbenicillin, ticarcillin, effective at lower doses), and Ureidopenicillins (piperacillin, mezlocillin, and azlocillin): Spectrum of activity similar to penicillin G, though having greater activity against gram-negative bacteria due to their enhanced ability to penetrate the gram-negative outer membrane. The aminopenicillins have the same spectrum and activity, but amoxicillin is better absorbed from the gut. These drugs are given orally to treat urinary tract infections, sinusitis, otitis, and lower respiratory tract infections. Ampicillin IV is useful for treating serious infections caused by penicillin-susceptible organisms, including anaerobes, enterococci, Listeria monocytogenes, and susceptible strains of gram-negative cocci and bacilli such as E coli, H influenzae, and Salmonella species. Carboxypenicillins extend the ampicillin spectrum of activity to include Pseudomonas aeruginosa and Enterobacter species. The ureidopenicillins resemble ticarcillin except that they are also active against selected gram-negative bacilli, such as Klebsiella pneumoniae. Because of the tendency of P aeruginosa to develop resistance during monotherapy, antipseudomonal penicillins generally is used in combination with an aminoglycoside for pseudomonal infections.
Adverse Reactions: Grouped into three: Allergy: Cross sensitivity and cross reactivity among beta-lactams is common. Reactions include: Skin rashes, fever, bronchospasm, Oral lesions, interstitial nephritis (autoimmune reaction to penicillin-protein complex), eosinophilia, hemolytic anemia, vasculitis and anaphylactic shock. Biological: antibiotic assoicated enterocolitis (ampicillin), and Toxic: diarrhea (ampicillin), nephritis, especially methicillin, and platelet dysfunction (antipseudomonal penicillins).
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