ANTIMICROBIALSMECHANISM OF ACTION

Dr.Elza Joy Munjely JR-I Depmt. Of Pharmacology Govt. Medical College,Kottayam.

CHEMOTHERAPY – treatment of systemic or topical infection with drugs that have selective toxicity for an invading pathogen without harming the host cells.

Takes advantage of the biochemical & physiological differences that exist between microorganism & human beings.

Antimicrobials Drugs that inhibit microbial growth &

multiplication Antibacterial Antiviral Antifungal Antiprotozoal Antihelminthics

Cidal/static Narrow/Extended/Broad spectrum

BACTERIOSTATICArrest the growth & replication & limit the spread of infection. Macrolides -Oxazolidones Chloramphinicol -Tetracyclines Sulphonamides -Trimethoprim Clindamycin -Nitrofurantoin Ethambutol -Linezolid Erythromycin

BACTERICIDALKill or irreversibly damage the multiplying bacteria. Betalactam -Vancomycin Polymixin -Bacitracin Isoniazid -Pyrazinamide Rifampicin -Aminoglycosides Nalidixic acid -Ciprofloxacin Metronidazole -Cotrimoxazole

Chloramphenicol - static against gram –ve rods & cidal against pneumococci

Sulphonamides/trimethoprim-static when used alone ,cidal when used in combination.

Cidal is preferred when host defences are impaired & for complicated infections.

BROAD SPECTRUM  effective against a wide range of infectious

microorganisms which includes gram positive, gram negative & atypical bacteria

Can be used emperically in case of serious infections

may give rise to drug resistance. Example

Tetracycline Chloramphenicol

NARROW SPECTRUM active against a selected group of bacterial

types.Either gram negative or gram positive. used for the specific infection when the

causative organism is known. cause less resistance of the bacteria as it will

deal with only specific bacteria. Examples:

Azithromycin Clarithromycin Clindamycin Erythromycin Vancomycin Streptomycin

EXTENDED-SPECTRUM ANTIBIOTIC  As a result of chemical modification,

affects additional types of bacteria ie, gram-negative + one or two gram positive & vice versa.

Examples- carboxypenicillins & urideopenicillins.

Targets of antimicrobials Cell wall Cell membrane Protein synthesis Intermediary metabolism Intracellular organelles Nucleic acid metabolism Muscle fibres

Cell wall synthesis inhibitors Bacteria – peptidoglycan

Inhibitors of peptidoglycan synthesisBetalactam,Vancomycin,Bacitracin,Cycloserin & Phosphomycin.

Mycobacteria – mycolic acid & arabinoglycans INH, Ethambutol, Pyrazinamide

Fungi – chitin Echinocandins

Cell membrane Cell membrane disrupting drugs

Anti-bacterial - polymixins Antifungal – polyene antibiotics

Inhibitors of cell membrane synthesis Azoles Terbinafine

Protein Synthesis

50s

rRNA•30s• Aminoglycosides, Tetracyclines ,Spectinomycin

•50s• Macrolides, Choramphenicol, Lincosamides,• Streptogramins, linezolid

tRNA•Mupirocin

Intermediary metabolism

DHF

THF

Nucleic acid synthesis

PABA

DHS

DHR

SulfonamidesDapsone

PAS

TrimethoprimPyrimethami

neProguanil

Trimetrexate

Intracellular organelles Mitotic spindle

Griseofulvin Benzimidazoles

Food vacuole Chloroquine, Quinine, Halofantrine,

Mefloquine Mitochondrial electron transport

chain Atovoquone

Muscle fibre

Ivermectin, Pyrantel pamoate, Piperazine

Nucleic acid RNA synthesis

RNA polymerase Rifampicin

DNA synthesis DNA gyrase

Quinolones DNA polymerase inhibitors

Acyclovir, Ganciclovir Reverse transcriptase

Anti HIV RT inhibitors DNA damage - metronidazole

PP

DHFA

PABA

THFA

DNA

m-RNA

INHIBITION OF DNA SYNTHESIS

Inhibits DNA gyraseFluroquinolones

DNA-directed RNA polymerase. Inhibits

RNA synthesisRifampicin

INHIBITION OF FOLIC ACID SYTHESIS

TrimethoprimPyrimethamine

ProguanilTrimetrexate

SulphonamidesDapsone

PAS,

Inhibition of 50 S

Chloramphenicol

MacrolidesClindamycinTelithromyci

nLinezolid

Streptogramins

Inhibition of 30 S

Aminoglycosides

TetracyclinesSpectinomyc

in

INHIBITION OF CELL WALL SYNTHESIS

Betalactams,Bacitracin,cycloserine

Vancomycin,TeicoplaninMonobactams,Carbopenems

,INH,Ethanbutol,Pyrazinamid

e

Alteration of cell membrane integrity

PolymixinsAmphotericin B

Azoles

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