ANTIMICROBIAL AGENTS

ANTIBIOTICS:

NATURAL COMPOUNDS PRODUCED BY MICROORGANISM WHICH INHIBIT THE GROWTH OF OTHER .

CHEMOTHERAPY:

SYNTHETIC COMPOUNDS.

SELECTIVE TOXICITY:SELECTIVE TOXICITY:

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 NARROW SPECTRUM: SELECTIVE ORGANISM.

THERAPEUTIC INDEX:THERAPEUTIC INDEX:

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 MECHANISMS OF ACTION OF ANTIMICROBIALSANTIMICROBIALS

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 ACTIONMECHANISMS OF ACTION

ANTIMICROBIALS THAT INHIBIT ANTIMICROBIALS THAT INHIBIT CELL WALL SYNTHESISCELL WALL SYNTHESIS

BETA LACTAMS

PENICILLINS CEPHALOSPORINS CARBAPENEMS MONOBACTAM

VANCOMYCIN BACITRACIN

FIG. 1

- LACTAM ANTIBIOTICS:- LACTAM ANTIBIOTICS:

BETA LACTAM RING &ORGANIC ACID. NATURAL &SEMISYNTHETIC CIDAL ACTION BIND TO PBP, INTERFERES WITH TRANSPEPTIDATION

REACTION

TOXICITY: HYPERSENS. ANAPHYLAXIS, DIARRHOEA, ..ETC.

PENICILLINS:PENICILLINS:

BENZYLE PENICILLIN:

PENIC. V, PROCAINE PEN., BENZATHIN PEN.

6-AMINOPENICILLANIC ACID:

CLOXACILLIN STAPH.

AMOXYCILLIN ENTEROBACTERIA

PIPERACILLIN PSEUDOMONAS

CEPHALOSPORINS:

FIRST GENERATIONS:

CEPHRADINE

SECOND GENERATIONS:

CEFUROXIME ,CEFOXITIN

THIRD GENERATIONS:

EXPANDED SPECTRUM

THIRD GEN: GRAM –VE ONLY CEFTRIAXONE CEFTAZIDIME

FOURTH GEN: CEFEPIM

CEFEXIME

VANCOMYCIN:VANCOMYCIN:

GLYCOPEPTIDE

CIDAL ON G +VE BACTERIA ONLY.

INHIBIT CELL WALL SYNTHESIS

INJ. ONLY.

USED FOR MRSA S.EDIDER. PESUDOMEM.COLITIS.

NEPHROTOXIC & OTOTOXIC.

ANTIBIOTICS THAT ALTER CELL ANTIBIOTICS THAT ALTER CELL MEMBRANESMEMBRANES

POLYMYXIN B

PEPTIDE ACTIVE AGAINST G –VE

BACTERICIDAL

ONLY USED LOCALLY DUE TO SERIOUS NEPHROTOXICITY

ANTIBIOTICS THAT INHIBIT PROTIEN ANTIBIOTICS THAT INHIBIT PROTIEN SYNTHESISSYNTHESIS

AMINOGLYCOSIDES

TETRACYCLINES

CHLORAMPHENICOL

MACROLIDES

AMINOGLYCOSIDES:

BACTERICIDAL

GRAM –VE BACTERIA

SRTEPT.& ANAEROBES RESISTANT

ACTION: INTERFER WITH BINDING OF t RNA TO 30 S SUBUNIT

GENTAMICIN, AMIKACIN, NEOMYCIN

INJECTABLE

NEPHROTOXIC& OTOTOXIC -DOSE RELATED

TETRACYCLINESTETRACYCLINES

BROAD SPECTRUM, STATIC ORAL ABSORPTION INTRACELLULAR EG. MYCOPLASMA, CHLAMYDIA

BRUCELLA ALSO FOR CHOLERA NOCARDIA

TWO CLASSES: SHORT ACTING: TETRACYCLINE LONG ACTING: MINOCYCLIN ,DOXY.

SIDE EFFECTS: TEETH DISCOLORATION, GIT DISTURBANCE

CHLORAMPHENICOLCHLORAMPHENICOL

BROAD SPECTRUM, CIDAL

BIND TO 50 s RIBOSOMAL SUBUNIT

AFFECT BONE MARROW CELLS AND CAUSE APLASTIC ANAEMIA

SEVERE INFECTIONS: TYPHOID FEVER, HI MENINGITIS, RICKETSIA…ETC.

MACROLIDES:

ERYTHROMYCIN & CLINDAMYCIN

BACTERIOSTATIC

LEGIONELLA, CAMPYLOBACTER, G +VE INFECTIONS IN PTS. ALLERGIC TO PEN.

CLINDAMYCIN ACT ON ANAEROBES

GIT DISTURBANCE, PMC (CLIND)

NEW MACROLIDES:

AZITHROMYCIN , CLARITHRIMYCIN

ANTIMICROBIALS THAT ACT ON NUCLEIC ACIDANTIMICROBIALS THAT ACT ON NUCLEIC ACID

RIFAMOICIN

QUINOLONES

METRONIDAZOLE

RIFAMPICIN:

SEMISYNTHETIC , CIDAL G +VE COCCI

RESERVED FOR TB

INHIBIT DNA DEP.RNA POLYMERASE

RESISTANCE DEVELOP QUICKLY

USED IN COMBINATION

DISCOLORATION OF BODY FLUIDS

HEPATOTOXIC

QUINOLONESQUINOLONES::

SYNTHETIC ,CIDAL, INHIBIT DNA GYRASE

NALIDIXIC ACID : OLD,G _VE ONLY

FLOUROQUINOLONES: CIPROFLOXACIN, NORFLOXACIN

SYSTEMIC INFECTIONS, UTI

BROAD EPECTRUM

BETTER PHARMACOLOGICALLY

AFFECT CARTILAGE IN ANIMALS

Fig. 3

ANTIMETABOLITES:ANTIMETABOLITES:

SULFONAMIDES

TRIMETHOPRIM

COMBINATION: BACTRIM/ SEPTRIN

BLOCK SEQUENTIAL STEPS IN FOLIC ACID SYNTHESIS

NOCARDIA,CHLAMYDIA,PROTOZOA,P.CRANII

UTI LRTI, OM..

GIT.HEPATITIS, BM DEPRESSIN, HYPERSENSITIVITY

ANTITUBERCULOUS AGENTS

FIRST LINE: INH RIFAMPICIN ETHAMBUTOL PYRAZINAMIDE

SECOND LINE:STREPTOMYCIN PASA CYCLOSERINE,CAPREOMYCIN

ISONIAZIDE (INH)

BATERICIDAL

INTRA& EXTRA CELLULAR MYCOBACTERIA

TREATMENT & PROPHYLAXIS

PREPHERAL NEURITIS

ETHAMBUTOL CIDAL CONC.IN

PHAGOLYSOSOME OF ALVEOLI

OPTIC NEURITIS

PYRAZINAMIDE ACID

ENVIRONMENT OF MACROPHAGES

HEPATITIS & ARTHRALGIA

ANTIBIOTIC RESISTANCE IN BACTERIAANTIBIOTIC RESISTANCE IN BACTERIA

INDISCRIMINATE USE OF ANTIMICROBIALS SELECTIVE ADVANTAGE OF ANTIBIOTICS

TYPES OF RESISTANCE:

PRIMARY:

INNATE eg. STREPT. &ANAEROBES RESISTANT TO GENTAMICIN

ANTIBIOTIC RESISTANCE IN BACTERIA (Continue)ANTIBIOTIC RESISTANCE IN BACTERIA (Continue)

AQUIRED: 1-MUTATION: MTB R TO SRTEPTOMYCIN

2- GENE TRANSFER: PLASMID MEDIATED OR TRANSPOSONES

CROSS RESISTANCE: R TO ONE GROUP CONFER R TO OTHER OF THE

SAME GROUP EG ERYTHROMYCIN & CLINDAMYCIN

DISSOCIATE R: R TO GENTA. DOES NOT CONFER R .TO

TOBRAMYCIN

MECHANISMS OR RESISTANCEMECHANISMS 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:PRINCIPLES OF ANTIMICROBIAL THERAPY:

INDICATION CHOICE OF DRUG ROUTE DOSAGE DURATION DISTRIBUTION EXCRETION TOXICITY COMBINATION PROPHYLAXIS:

SHORT TERM: MENINGITISLONG TERM: TB, UTI , RHEUMATIC

FEVER

CRITERIA FOR IDEAL ANTIMICROBIAL:CRITERIA FOR IDEAL ANTIMICROBIAL:

SELECTIVE TOXICITY

NO HYPERSENSITIVITY

PENETERATE TISSUES QUICKLY

RESISTANCE NOT DEVELOP QUICKLY

NO EFFECT ON NORMAL FLORA

BROAD SPECTRUM

ANTIFUNGAL AGENTS:

NYSTATIN LOCAL AMPHOTERICIN B SYSTEMIC

ANTIVIRAL AGENTS IODOXURIDINE VIDARABINE AMANTADINE INTERFERON