ANTIMICROBIAL AGENTS

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ANTIMICROBIAL AGENTS

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

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SELECTIVE TOXICITY

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

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

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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

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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.

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MECHANISMS OF ACTION
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ANTIMICROBIALS THAT INHIBIT CELL WALL SYNTHESIS

• BETA LACTAMS
• PENICILLINS
• CEPHALOSPORINS
• CARBAPENEMS
• MONOBACTAM
• VANCOMYCIN
• BACITRACIN

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FIG. 1
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? - LACTAM ANTIBIOTICS

• BETA LACTAM RING ORGANIC ACID.
• NATURAL SEMISYNTHETIC
• CIDAL ACTION
• BIND TO PBP, INTERFERES WITH TRANSPEPTIDATION
  REACTION
• TOXICITY
• HYPERSENS.
• ANAPHYLAXIS,
• DIARRHOEA, ..ETC.

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(No Transcript)
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PENICILLINS

• BENZYLE PENICILLIN
• PENIC. V,
• PROCAINE PEN.,
• BENZATHIN PEN.
• 6-AMINOPENICILLANIC ACID
• CLOXACILLIN STAPH.
• AMOXYCILLIN ENTEROBACTERIA
• PIPERACILLIN PSEUDOMONAS

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CEPHALOSPORINS

• FIRST GENERATIONS
• CEPHRADINE
• SECOND GENERATIONS
• CEFUROXIME ,CEFOXITIN
• THIRD GENERATIONS
• EXPANDED SPECTRUM

• THIRD GEN
• GRAM VE ONLY
• CEFTRIAXONE
• CEFTAZIDIME
• FOURTH GEN
• CEFEPIM
• CEFEXIME

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VANCOMYCIN

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

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ANTIBIOTICS THAT ALTER CELL MEMBRANES

• POLYMYXIN B
• PEPTIDE ACTIVE AGAINST G VE
• BACTERICIDAL
• ONLY USED LOCALLY DUE TO SERIOUS NEPHROTOXICITY

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ANTIBIOTICS THAT INHIBIT PROTIEN SYNTHESIS

• AMINOGLYCOSIDES
• TETRACYCLINES
• CHLORAMPHENICOL
• MACROLIDES

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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

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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

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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.

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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

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ANTIMICROBIALS THAT ACT ON NUCLEIC ACID

• RIFAMOICIN
• QUINOLONES
• METRONIDAZOLE

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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

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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

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Fig. 3
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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

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ANTITUBERCULOUS AGENTS

• FIRST LINE INH
• RIFAMPICIN
• ETHAMBUTOL
• PYRAZINAMIDE

• SECOND LINE
• STREPTOMYCIN
• PASA
• CYCLOSERINE,
• CAPREOMYCIN

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ISONIAZIDE (INH)

• BATERICIDAL
• INTRA EXTRA CELLULAR MYCOBACTERIA
• TREATMENT PROPHYLAXIS
• PREPHERAL NEURITIS

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• PYRAZINAMIDE
• ACID ENVIRONMENT OF MACROPHAGES
• HEPATITIS ARTHRALGIA

• ETHAMBUTOL
• CIDAL
• CONC.IN PHAGOLYSOSOME OF ALVEOLI
• OPTIC NEURITIS

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ANTIBIOTIC RESISTANCE IN BACTERIA

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

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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

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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.

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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

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CRITERIA FOR IDEAL ANTIMICROBIAL

• SELECTIVE TOXICITY
• NO HYPERSENSITIVITY
• PENETERATE TISSUES QUICKLY
• RESISTANCE NOT DEVELOP QUICKLY
• NO EFFECT ON NORMAL FLORA
• BROAD SPECTRUM

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ANTIFUNGAL AGENTS

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