PHTH1011 007 Microbial Chemotherapy - Williams.pdf

Microbial Chemotherapy (1 hr) Lecturer: Prof. Maxine Gossell-Williams, UWI, Pharmacology Section Email:[email protected] Course Objectives To give students an understanding of the pharmacology of amoxicillin, c gentamicin and tetracyclines At the end of lecture students would have covere...

Microbial Chemotherapy (1 hr) Lecturer: Prof. Maxine Gossell-Williams, UWI, Pharmacology Section Email:[email protected] Course Objectives To give students an understanding of the pharmacology of amoxicillin, c gentamicin and tetracyclines At the end of lecture students would have covered: chemistry, mechanism of action, spectrum of activity, pharmacokinetics, development of resistance related to each drug discussed Points to note Penicillins Chemistry: Originally obtained from Penicillium chrysogenum (a fungus). Consist of Beta-lactam ring (responsible for activity) eg AMOXICILLLIN Penicillins MOA: Inhibit formation of new cell wall…..BACTERICIDAL EXAMPLES SPECTRUM BENZYLPENICILLIN (PEN G) Narrow AMOXICILLIN Broad Clinical applications include: UTI, syphilis, typhoid fever, rheumatic fever, bacterial endocarditis, ect. ABSORPTION/DISTRIBUTION METABOLISM/ Amoxicillin..Oral ELIMINATION Readily distributed into body fluids and cross placenta Excreted mainly unchanged renally ADR RESISTANCE Breaking of the beta-lactam ring by beta-lactamases of bacteria Generally safe- allergic rxns (rashes, pruritus, anaphylaxis) Aminoglycosides Eg. GENTAMICIN Chemistry: Polar compounds which contain amino sugars. (eg. Streptomycin) MOA: Irreversible inhibition of protein synthesis…BACTERICIDAL CLINICAL APPLICATIONS: Spectrum: aerobic bacteria Mycobacterial infections Staphylococcal infections ABSORPTION/DISTRIBUTION high polarity does not allow for passage across membranes not absorbed O Given parenterally do not penetrate cells, tissues. however, concentrate into renal cortical tissue, endolymph and perilymph. Low PPB METABOLISM/ ELIMINATION Excreted unchanged renally ADR Low TI Pain at injection site Nephrotoxic after one week administration (reversible with discontinuation) Ototoxic (degeneration of auditory fibres, tinnitus, deafness) NMJ blockage-decrease Ach release Allergic Rxn- rashes and fever RESISTANCE Transferases in bacteria break down the drug Tetracyclines Chemistry Four member ring compounds. Eg TETRACYCLINE MINOCYCLINE MOA: Reversible inhibition of protein synthesis.......................BACTERISTATIC CLINICAL APPLICATIONS SPECTRUM Chlamydia, Cholera, Rickettsia Broad Spectrum Propionibacterium (Acne) ABSORPTION/DISTRIBUTION METABOLISM/ ELIMINATION Well absorbed from GIT Excreted unchanged renally Affected by food and metal ions (least for minocycline) ADR Also given IV Polyurea high lipid solubility Photosensitivity generally accumulate well in body fluid and tissues Contraindicated in children and pregnancy Peak serum levels in 2 hrs. with O. Low accumulation in CSF, crosses placenta Chelates with metal ions, Calcium RESISTANCE Increased efflux/Decreased influx of the drug Hepatotoxicity in pregnancy (fatal) Superinfections – diarrhoea, thrush, vaginal candidiasis