Amoxicillin Pharmacology

• Focus is on the pharmacology of amoxicillin, gentamicin, and tetracyclines.
• The following points will be covered: chemistry, mechanism of action, spectrum of activity, pharmacokinetics, and development of resistance for each drug.

Penicillins

• Originally derived from Penicillium chrysogenum, a fungus.
• Consist of a beta-lactam ring, which is responsible for the drug's activity.
• Amoxicillin is an example.
• The mechanism of action involves inhibiting the formation of the new cell wall, making it bactericidal.
• Benzylpenicillin (Pen G) has a narrow spectrum
• Amoxicillin has a broad spectrum
• Clinical applications include: UTI, syphilis, typhoid fever, rheumatic fever, bacterial endocarditis, etc.
• Amoxicillin is administered orally.
• It is readily distributed into body fluids and can cross the placenta.
• Excreted mainly unchanged renally.
• Resistance develops through the breaking of the beta-lactam ring by beta-lactamases produced by bacteria.
• Generally safe, but can cause allergic reactions such as rashes, pruritus, and anaphylaxis.

Aminoglycosides

• Gentamicin is an example.
• Polar compounds containing amino sugars, like Streptomycin.
• Irreversibly inhibits protein synthesis, and is bactericidal.
• Effective against aerobic bacteria.
• Clinical applications: Mycobacterial and Staphylococcal infections.
• High polarity, therefore it does not allow for passage across membranes
• Usually given parenterally
• Does not penetrate cells and tissues
• However, concentrate into renal cortical tissue, endolymph, and perilymph.
• Low PPB
• Excreted unchanged renally.
• Low TI
• Can cause pain at the injection site.
• Nephrotoxicity after one week of administration (reversible with discontinuation).
• Ototoxic (degeneration of auditory fibers, tinnitus, deafness).
• NMJ blockage-decrease Ach release
• Allergic reactions like rashes and fever can occur.
• Resistance develops as transferases in bacteria break down the drug.

Tetracyclines

• Chemistry: Four-member ring compounds.
• Examples: Tetracycline, Minocycline.
• It reversibly inhibits protein synthesis, which is bacteriostatic.
• Its spectrum of activity is broad.
• Clinical applications include Chlamydia, Cholera, Rickettsia, and Propionibacterium (Acne).
• Well absorbed from the gastrointestinal tract (GIT).
• Absorption is affected by food and metal ions (least affected for minocycline).
• Also can be given intravenously
• High lipid solubility.
• It generally accumulates well in body fluid and tissues.
• Peak serum levels reached in 2 hours.
• Low accumulation in CSF and crosses the placenta.
• Chelates with metal ions, and calcium.
• Excreted unchanged renally.
• Can have adverse drug reactions like polyuria and photosensitivity.
• Contraindicated in children and during pregnancy.
• Hepatotoxicity in pregnancy can be fatal.
• Superinfections such as diarrhea, thrush, and vaginal candidiasis can occur.
• Resistance develops through increased efflux and decreased influx of the drug.