Transcript ANTIMICROBIAL AGENTS ANTIBIOTICS: CHEMOTHERAPY: NATURAL

ANTIMICROBIAL AGENTS
ANTIBIOTICS:

NATURAL
COMPOUNDS
PRODUCED
BY
MICROORGANISM WHICH INHIBIT THE GROWTH
OF OTHER .
CHEMOTHERAPY:

SYNTHETIC COMPOUNDS.
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:

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

BETA LACTAMS
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PENICILLINS
CEPHALOSPORINS
CARBAPENEMS
MONOBACTAM
VANCOMYCIN
BACITRACIN
FIG. 1
 - LACTAM ANTIBIOTICS:

BETA LACTAM RING &ORGANIC ACID.
 NATURAL &SEMISYNTHETIC
 CIDAL ACTION
 BIND TO PBP, INTERFERES WITH TRANSPEPTIDATION
REACTION
TOXICITY:
 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:
 GRAM –VE ONLY
 CEFTRIAXONE
 CEFTAZIDIME
FOURTH GEN:
 CEFEPIM
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CEFEXIME
VANCOMYCIN:

GLYCOPEPTIDE
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CIDAL ON G +VE BACTERIA ONLY.
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INHIBIT CELL WALL SYNTHESIS
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INJ. ONLY.
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USED FOR MRSA S.EDIDER. PESUDOMEM.COLITIS.
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NEPHROTOXIC & OTOTOXIC.
ANTIBIOTICS THAT ALTER CELL
MEMBRANES

POLYMYXIN B

PEPTIDE ACTIVE AGAINST G –VE

BACTERICIDAL
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ONLY USED LOCALLY DUE TO SERIOUS
NEPHROTOXICITY
ANTIBIOTICS THAT INHIBIT PROTIEN
SYNTHESIS
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AMINOGLYCOSIDES
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TETRACYCLINES
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CHLORAMPHENICOL
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MACROLIDES
AMINOGLYCOSIDES:
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BACTERICIDAL
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GRAM –VE BACTERIA
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SRTEPT.& ANAEROBES RESISTANT
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ACTION: INTERFER WITH BINDING OF t RNA TO 30 S SUBUNIT
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GENTAMICIN, AMIKACIN, NEOMYCIN
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INJECTABLE
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NEPHROTOXIC& OTOTOXIC -DOSE RELATED
TETRACYCLINES
 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
CHLORAMPHENICOL
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BROAD SPECTRUM, CIDAL
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BIND TO 50 s RIBOSOMAL SUBUNIT
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AFFECT BONE MARROW CELLS AND CAUSE
APLASTIC ANAEMIA
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SEVERE INFECTIONS: TYPHOID FEVER, HI
MENINGITIS, RICKETSIA…ETC.
MACROLIDES:

ERYTHROMYCIN & CLINDAMYCIN
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BACTERIOSTATIC
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LEGIONELLA, CAMPYLOBACTER, G +VE INFECTIONS IN PTS.
ALLERGIC TO PEN.
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CLINDAMYCIN ACT ON ANAEROBES
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GIT DISTURBANCE, PMC (CLIND)
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NEW MACROLIDES:
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AZITHROMYCIN , CLARITHRIMYCIN
ANTIMICROBIALS THAT ACT ON NUCLEIC ACID
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RIFAMOICIN
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QUINOLONES
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METRONIDAZOLE
RIFAMPICIN:
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SEMISYNTHETIC , CIDAL G +VE COCCI
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RESERVED FOR TB
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INHIBIT DNA DEP.RNA POLYMERASE
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RESISTANCE DEVELOP QUICKLY
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USED IN COMBINATION
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DISCOLORATION OF BODY FLUIDS
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HEPATOTOXIC
QUINOLONES:
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SYNTHETIC ,CIDAL, INHIBIT DNA GYRASE
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NALIDIXIC ACID : OLD,G _VE ONLY
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FLOUROQUINOLONES: CIPROFLOXACIN, NORFLOXACIN
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SYSTEMIC INFECTIONS, UTI
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BROAD EPECTRUM
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BETTER PHARMACOLOGICALLY
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AFFECT CARTILAGE IN ANIMALS
Fig. 3
ANTIMETABOLITES:
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SULFONAMIDES
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TRIMETHOPRIM
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COMBINATION: BACTRIM/ SEPTRIN
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BLOCK SEQUENTIAL STEPS IN FOLIC ACID SYNTHESIS
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NOCARDIA,CHLAMYDIA,PROTOZOA,P.CRANII

UTI LRTI, OM..
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GIT.HEPATITIS, BM DEPRESSIN, HYPERSENSITIVITY
ANTITUBERCULOUS AGENTS
FIRST LINE: INH
 RIFAMPICIN
 ETHAMBUTOL
 PYRAZINAMIDE
SECOND LINE:
STREPTOMYCIN
PASA
CYCLOSERINE,
CAPREOMYCIN
ISONIAZIDE (INH)
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BATERICIDAL
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INTRA& EXTRA CELLULAR MYCOBACTERIA
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TREATMENT & PROPHYLAXIS

PREPHERAL NEURITIS
ETHAMBUTOL
 CIDAL
 CONC.IN
PHAGOLYSOSOME OF
ALVEOLI
 OPTIC NEURITIS
PYRAZINAMIDE
 ACID
ENVIRONMENT OF
MACROPHAGES
 HEPATITIS &
ARTHRALGIA
ANTIBIOTIC 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)
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 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:
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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:
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SELECTIVE TOXICITY

NO HYPERSENSITIVITY
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PENETERATE TISSUES QUICKLY
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RESISTANCE NOT DEVELOP QUICKLY
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NO EFFECT ON NORMAL FLORA
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BROAD SPECTRUM
ANTIFUNGAL AGENTS:
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NYSTATIN
LOCAL
AMPHOTERICIN B
ANTIVIRAL AGENTS

IODOXURIDINE
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VIDARABINE
 AMANTADINE

INTERFERON
SYSTEMIC