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ANTIMICROBIAL AGENTS

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Title: ANTIMICROBIAL AGENTS


1
ANTIMICROBIAL AGENTS
  • ANTIBIOTICS
  • NATURAL COMPOUNDS PRODUCED BY MICROORGANISM WHICH
    INHIBIT THE GROWTH OF OTHER .
  • CHEMOTHERAPY
  • SYNTHETIC COMPOUNDS.

2
SELECTIVE TOXICITY
  • THE ABILITY TO KILL OR INHIBIT THE GROWTH OF
    MICROORGANISM WITHOUT HARMING THE HOST CELLS.

3
  • BACTERICIDAL KILLS BACTERIA
  • BACTERIOSTATIC PREVENTS MULTIPLICATION.
  • SPECTRIM OF ACTIVITY
  • BROAD SPECTRUM GVE G-VE
  • NARROW SPECTRUM SELECTIVE ORGANISM.

4
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

5
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.

6
MECHANISMS OF ACTION
7
ANTIMICROBIALS THAT INHIBIT CELL WALL SYNTHESIS
  • BETA LACTAMS
  • PENICILLINS
  • CEPHALOSPORINS
  • CARBAPENEMS
  • MONOBACTAM
  • VANCOMYCIN
  • BACITRACIN

8
FIG. 1
9
? - LACTAM ANTIBIOTICS
  • BETA LACTAM RING ORGANIC ACID.
  • NATURAL SEMISYNTHETIC
  • CIDAL ACTION
  • BIND TO PBP, INTERFERES WITH TRANSPEPTIDATION
    REACTION
  • TOXICITY
  • HYPERSENS.
  • ANAPHYLAXIS,
  • DIARRHOEA, ..ETC.

10
(No Transcript)
11
PENICILLINS
  • BENZYLE PENICILLIN
  • PENIC. V,
  • PROCAINE PEN.,
  • BENZATHIN PEN.
  • 6-AMINOPENICILLANIC ACID
  • CLOXACILLIN STAPH.
  • AMOXYCILLIN ENTEROBACTERIA
  • PIPERACILLIN PSEUDOMONAS

12
CEPHALOSPORINS
  • FIRST GENERATIONS
  • CEPHRADINE
  • SECOND GENERATIONS
  • CEFUROXIME ,CEFOXITIN
  • THIRD GENERATIONS
  • EXPANDED SPECTRUM
  • THIRD GEN
  • GRAM VE ONLY
  • CEFTRIAXONE
  • CEFTAZIDIME
  • FOURTH GEN
  • CEFEPIM
  • CEFEXIME

13
VANCOMYCIN
  • GLYCOPEPTIDE
  • CIDAL ON G VE BACTERIA ONLY.
  • INHIBIT CELL WALL SYNTHESIS
  • INJ. ONLY.
  • USED FOR MRSA S.EDIDER. PESUDOMEM.COLITIS.
  • NEPHROTOXIC OTOTOXIC.

14
ANTIBIOTICS THAT ALTER CELL MEMBRANES
  • POLYMYXIN B
  • PEPTIDE ACTIVE AGAINST G VE
  • BACTERICIDAL
  • ONLY USED LOCALLY DUE TO SERIOUS NEPHROTOXICITY

15
ANTIBIOTICS THAT INHIBIT PROTIEN SYNTHESIS
  • AMINOGLYCOSIDES
  • TETRACYCLINES
  • CHLORAMPHENICOL
  • MACROLIDES

16
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

17
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

18
CHLORAMPHENICOL
  • BROAD SPECTRUM, CIDAL
  • BIND TO 50 s RIBOSOMAL SUBUNIT
  • AFFECT BONE MARROW CELLS AND CAUSE APLASTIC
    ANAEMIA
  • SEVERE INFECTIONS TYPHOID FEVER, HI MENINGITIS,
    RICKETSIAETC.

19
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

20
ANTIMICROBIALS THAT ACT ON NUCLEIC ACID
  • RIFAMOICIN
  • QUINOLONES
  • METRONIDAZOLE

21
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

22
QUINOLONES
  • 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

23
Fig. 3
24
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

25
ANTITUBERCULOUS AGENTS
  • FIRST LINE INH
  • RIFAMPICIN
  • ETHAMBUTOL
  • PYRAZINAMIDE
  • SECOND LINE
  • STREPTOMYCIN
  • PASA
  • CYCLOSERINE,
  • CAPREOMYCIN

26
ISONIAZIDE (INH)
  • BATERICIDAL
  • INTRA EXTRA CELLULAR MYCOBACTERIA
  • TREATMENT PROPHYLAXIS
  • PREPHERAL NEURITIS

27
  • PYRAZINAMIDE
  • ACID ENVIRONMENT OF MACROPHAGES
  • HEPATITIS ARTHRALGIA
  • ETHAMBUTOL
  • CIDAL
  • CONC.IN PHAGOLYSOSOME OF ALVEOLI
  • OPTIC NEURITIS

28
ANTIBIOTIC RESISTANCE IN BACTERIA
  • INDISCRIMINATE USE OF ANTIMICROBIALS
  • SELECTIVE ADVANTAGE OF ANTIBIOTICS
  • TYPES OF RESISTANCE
  • PRIMARY
  • INNATE eg. STREPT. ANAEROBES RESISTANT TO
    GENTAMICIN

29
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

30
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.

31
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

32
CRITERIA FOR IDEAL ANTIMICROBIAL
  • SELECTIVE TOXICITY
  • NO HYPERSENSITIVITY
  • PENETERATE TISSUES QUICKLY
  • RESISTANCE NOT DEVELOP QUICKLY
  • NO EFFECT ON NORMAL FLORA
  • BROAD SPECTRUM

33
ANTIFUNGAL AGENTS
  • NYSTATIN LOCAL
  • AMPHOTERICIN B SYSTEMIC
  • ANTIVIRAL AGENTS
  • IODOXURIDINE
  • VIDARABINE
  • AMANTADINE
  • INTERFERON
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