ANTIMICROBIAL AGENTS ANTIBIOTICS NATURAL COMPOUNDS PRODUCED BY MICROORGANISM
ANTIMICROBIAL AGENTS ANTIBIOTICS: Ø NATURAL COMPOUNDS PRODUCED BY MICROORGANISM WHICH INHIBIT THE GROWTH OF OTHER. CHEMOTHERAPY: Ø SYNTHETIC COMPOUNDS.
SELECTIVE TOXICITY: Ø THE ABILITY TO KILL OR INHIBIT THE GROWTH OF MICROORGANISM WITHOUT HARMING THE HOST CELLS.
BACTERICIDAL: KILLS BACTERIA BACTERIOSTATIC: PREVENTS MULTIPLICATION. SPECTRIM OF ACTIVITY: BROAD SPECTRUM: G+VE& G-VE Ø NARROW SPECTRUM: SELECTIVE ORGANISM. Ø
THERAPEUTIC INDEX: Ø THE RATIO OF THE DOSE TOXIC TO THE HOST TO THE EFFECTIVE THERAPEUTIC DOSE. EXAMPLES: § PENICILLIN: HIGH § AMINOGLYCOSIDES: LOW § POLYMYXIN B: THE LOWEST
MECHANISMS OF ACTION OF ANTIMICROBIALS 1) INHIBITION OF CELL WALL SYNTHESIS. 2) ALTERATION OF CELL MEMBRANES 3) INHIBITION OF PROTEIN SYNTHSIS 4) INHIBITION OF NUCLEIC ACID 5) ANTIMETABOLIC OR COMPETITEVE ANTAGONISM.
MECHANISMS OF ACTION
ANTIMICROBIALS THAT INHIBIT CELL WALL SYNTHESIS Ø BETA LACTAMS § § PENICILLINS CEPHALOSPORINS CARBAPENEMS MONOBACTAM VANCOMYCIN Ø BACITRACIN Ø
FIG. 1
- LACTAM ANTIBIOTICS: BETA LACTAM RING &ORGANIC ACID. Ø NATURAL &SEMISYNTHETIC Ø CIDAL ACTION Ø BIND TO PBP, INTERFERES WITH TRANSPEPTIDATION REACTION TOXICITY: Ø § HYPERSENS. § ANAPHYLAXIS, § DIARRHOEA, . . ETC.
PENICILLINS: BENZYLE PENICILLIN: § PENIC. V, § PROCAINE PEN. , § BENZATHIN PEN. 6 -AMINOPENICILLANIC ACID: CLOXACILLIN AMOXYCILLIN PIPERACILLIN STAPH. ENTEROBACTERIA PSEUDOMONAS
CEPHALOSPORINS: FIRST GENERATIONS: CEPHRADINE SECOND GENERATIONS: CEFUROXIME , CEFOXITIN THIRD GENERATIONS: EXPANDED SPECTRUM THIRD GEN: Ø GRAM –VE ONLY Ø CEFTRIAXONE Ø CEFTAZIDIME FOURTH GEN: Ø CEFEPIM Ø Ø CEFEXIME
VANCOMYCIN: Ø GLYCOPEPTIDE Ø CIDAL ON G +VE BACTERIA ONLY. Ø INHIBIT CELL WALL SYNTHESIS Ø INJ. ONLY. Ø USED FOR MRSA S. EDIDER. PESUDOMEM. COLITIS. Ø NEPHROTOXIC & OTOTOXIC.
ANTIBIOTICS THAT ALTER CELL MEMBRANES Ø POLYMYXIN B Ø PEPTIDE ACTIVE AGAINST G –VE Ø BACTERICIDAL Ø ONLY USED LOCALLY DUE TO SERIOUS NEPHROTOXICITY
ANTIBIOTICS THAT INHIBIT PROTIEN SYNTHESIS Ø AMINOGLYCOSIDES Ø TETRACYCLINES Ø CHLORAMPHENICOL Ø MACROLIDES
AMINOGLYCOSIDES: Ø BACTERICIDAL Ø GRAM –VE BACTERIA Ø SRTEPT. & ANAEROBES RESISTANT Ø ACTION: INTERFER WITH BINDING OF t RNA TO 30 S SUBUNIT Ø GENTAMICIN, AMIKACIN, NEOMYCIN Ø INJECTABLE Ø NEPHROTOXIC& OTOTOXIC -DOSE RELATED
TETRACYCLINES Ø BROAD SPECTRUM, STATIC Ø ORAL ABSORPTION Ø INTRACELLULAR EG. MYCOPLASMA, CHLAMYDIA BRUCELLA ALSO FOR CHOLERA NOCARDIA TWO CLASSES: Ø SHORT ACTING: TETRACYCLINE Ø LONG ACTING: MINOCYCLIN , DOXY. SIDE EFFECTS: Ø TEETH DISCOLORATION, GIT DISTURBANCE
CHLORAMPHENICOL Ø BROAD SPECTRUM, CIDAL Ø BIND TO 50 s RIBOSOMAL SUBUNIT Ø AFFECT BONE MARROW CELLS AND CAUSE APLASTIC ANAEMIA Ø SEVERE INFECTIONS: TYPHOID FEVER, HI MENINGITIS, RICKETSIA…ETC.
MACROLIDES: Ø ERYTHROMYCIN & CLINDAMYCIN Ø BACTERIOSTATIC Ø LEGIONELLA, CAMPYLOBACTER, G +VE INFECTIONS IN PTS. ALLERGIC TO PEN. Ø CLINDAMYCIN ACT ON ANAEROBES Ø GIT DISTURBANCE, PMC (CLIND) Ø NEW MACROLIDES: Ø AZITHROMYCIN , CLARITHRIMYCIN
ANTIMICROBIALS THAT ACT ON NUCLEIC ACID Ø RIFAMOICIN Ø QUINOLONES Ø METRONIDAZOLE
RIFAMPICIN: Ø SEMISYNTHETIC , CIDAL G +VE COCCI Ø RESERVED FOR TB Ø INHIBIT DNA DEP. RNA POLYMERASE Ø RESISTANCE DEVELOP QUICKLY Ø USED IN COMBINATION Ø DISCOLORATION OF BODY FLUIDS Ø HEPATOTOXIC
QUINOLONES: Ø SYNTHETIC , CIDAL, INHIBIT DNA GYRASE Ø NALIDIXIC ACID : OLD, G _VE ONLY Ø FLOUROQUINOLONES: CIPROFLOXACIN, NORFLOXACIN Ø SYSTEMIC INFECTIONS, UTI Ø BROAD EPECTRUM Ø BETTER PHARMACOLOGICALLY Ø AFFECT CARTILAGE IN ANIMALS
Fig. 3
ANTIMETABOLITES: Ø SULFONAMIDES Ø TRIMETHOPRIM Ø COMBINATION: BACTRIM/ SEPTRIN Ø BLOCK SEQUENTIAL STEPS IN FOLIC ACID SYNTHESIS Ø NOCARDIA, CHLAMYDIA, PROTOZOA, P. CRANII Ø UTI LRTI, OM. . Ø GIT. HEPATITIS, BM DEPRESSIN, HYPERSENSITIVITY
ANTITUBERCULOUS AGENTS FIRST LINE: INH Ø RIFAMPICIN Ø ETHAMBUTOL Ø PYRAZINAMIDE SECOND LINE: ØSTREPTOMYCIN ØPASA ØCYCLOSERINE, ØCAPREOMYCIN
ISONIAZIDE (INH) Ø BATERICIDAL Ø INTRA& EXTRA CELLULAR MYCOBACTERIA Ø TREATMENT & PROPHYLAXIS Ø PREPHERAL NEURITIS
ETHAMBUTOL § CIDAL § CONC. IN PHAGOLYSOSOME OF ALVEOLI § OPTIC NEURITIS PYRAZINAMIDE § ACID ENVIRONMENT OF MACROPHAGES § HEPATITIS & ARTHRALGIA
ANTIBIOTIC RESISTANCE IN BACTERIA Ø INDISCRIMINATE USE OF ANTIMICROBIALS Ø SELECTIVE ADVANTAGE OF ANTIBIOTICS TYPES OF RESISTANCE: PRIMARY: Ø INNATE eg. STREPT. &ANAEROBES RESISTANT TO GENTAMICIN
ANTIBIOTIC RESISTANCE IN BACTERIA (Continue) AQUIRED: Ø 1 -MUTATION: MTB R TO SRTEPTOMYCIN 2 - GENE TRANSFER: PLASMID MEDIATED OR TRANSPOSONES CROSS RESISTANCE: Ø R TO ONE GROUP CONFER R TO OTHER OF THE SAME GROUP Ø EG ERYTHROMYCIN & CLINDAMYCIN DISSOCIATE R: Ø R TO GENTA. DOES NOT CONFER R. TO TOBRAMYCIN Ø
MECHANISMS OR RESISTANCE 1 -PERMIABILITY CANGED 2 -MODIFICATION OF SITE OF ACTION, EG. MUTATION 3 -INACTIVATION BY ENZYMES. EG. BETA LACTAMASE, AMINOGLYCOSIDES INACTIVATING ENZYMES BYPASSING BLOCKED METABOLIC REACTION EG. PABA FOILC ACID BY PLASMID MEDIATED DFR.
PRINCIPLES OF ANTIMICROBIAL THERAPY: § § § § § INDICATION CHOICE OF DRUG ROUTE DOSAGE DURATION DISTRIBUTION EXCRETION TOXICITY COMBINATION PROPHYLAXIS: SHORT TERM: § MENINGITIS LONG TERM: § TB, UTI , RHEUMATIC FEVER
CRITERIA FOR IDEAL ANTIMICROBIAL: Ø SELECTIVE TOXICITY Ø NO HYPERSENSITIVITY Ø PENETERATE TISSUES QUICKLY Ø RESISTANCE NOT DEVELOP QUICKLY Ø NO EFFECT ON NORMAL FLORA Ø BROAD SPECTRUM
ANTIFUNGAL AGENTS: NYSTATIN Ø AMPHOTERICIN B Ø ANTIVIRAL AGENTS Ø IODOXURIDINE Ø VIDARABINE Ø AMANTADINE Ø INTERFERON LOCAL SYSTEMIC
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