A PRESENTATION BY SURYA PRAJAPAT

ANTIBIOTICS SURYA

ANTIBIOTICS

ANTIBIOTICS SURYA

INDEX

1. INTRODUCTION

2. CLASSIFICATION

3. DESCRIPTIONS & MODE OF ACTION

• Β-LACTAM

• AMINOGLYCOSIDES

• MACROLIDES

• TETRACYCLIN

• CHLORAMPHENICOL

• GLYCOPEPTIDES

• OXAZOLIDINONE

• LINCOSAMIDES

• FLUOROQUINOLONES

• OTHERS

4. RISISTANCE TO ANTIBIOTICS

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INTRODUCTION

• Antibiotics (Greek anti, “against”; bios, “life”) are chemical compounds used to kill or inhibit the growth of infectious organisms. Originally the term antibiotic referred only to organic compounds, produced by bacteria or molds, that are toxic to other microorganisms.

• They are more toxic to an invading organism than they are to an animal or human host.

• first antibiotic was penicillin, discovered accidentally from a mold culture.

• Antibiotics only treat bacterial infections. Antibiotics are useless against viral infections (for example, the common cold) and fungal infections (such as ringworm).

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• CLASSIFICATION:

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• classification by their mechanism of action:

1. Inhibit bacterial cell wall synthesis: Penicillin

Cephalosporin

Cycloserin

Vancomycin

2. Cause leakage from cell membrane: Polypeptides polyenes

Polymixin AmphotericinB

Colistin Nystatin

Bacitracin Hamycin

3. Cause misreading of m-RNA code

and affect permeability : Aminoglycosides

Streptomycin

Gentamycin

Neomycin

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4. Inhibit protein synthesis: Tetracyclin

Chloramphenicol

Erythromycin

Clindamycin

Linezolid

5. Inhibit DNA gyrase: Fluoroquinolones

Ciprofloxacin

Norfloxacin

Ofloxacin

6. Interfere with metabolism : Sulfonamides

Ethambutol

7. Interfere with DNA function : Rifampin

8. Interfere with DNA synthesis : Metronidazole

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DESCRIPTIONS:

1. Β-Lactam antibiotics:

Penicillin

Cephalosporin

Carbapenems : Imipenem, Meropenem, Faropenem

A. PENICILLIN: Penicillin was the first antibiotic to be used clinically in 1941. It was originally obtained from fungus Penicillium notatum.

Mechanism of action:

Binds to Penicillin-binding protein

Inhibit the Transpeptidase activity in cell wall formation

Transpeptidation i.e cross linking between peptides not occur.

Peptidoglycan cell wall not form. bacterial cell wall synthesis inhibited.

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• Eg: Penicillin G Uses:

Penicillin V streptococcal infection

Naficillin pneumococcal infection

Methicillin meningococcal infection

Ampicillin gonorrhea, syphilis

Amoxycillin Diphtheria

Tetanus

gas gangrene

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B. CEPHALOSPORIN : These are group of semisynthetic antibiotics derived from Cephalosporin-C obtained from a fungus Cephalosporium. They are chemically related to penicillin. Its nucleus consist of β-lactum ring.

• Their MOA is same as penicillin, i.e inhibition of bacterial cell wall synthesis. All cephalosporins are bactericidal.

Cephalosporin

Ist gen: Cephalexin, cephalothin, Cephadroxil

IInd gen: Cefaclor,

Cefuroxime, Cefoxitin

IIIrd gen: Cefixime,

Cefpodoxime, Ceftriaxone,

Cefdinir

IVth gen: Cefepime, Cefpirome

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• Ist generation:

Broad spectrum than Penicillin.

Active against both gram+ve and gram-ve organisms.

• IInd generation:

Active against many gram-ve organisms which are resistant to Ist generation.

• IIIrd generation:

Gram+ve : less active than Ist generation

Gram -ve : more active.

• IVth generation:

Gram +ve : more active than IIIrd generation.

Gram –ve : excellent active against gram –ve.

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2. AMINOGLYCOSIDES: Aminoglycosides are the drugs effective against gram-ve bacteria. All aminoglycosides are produced by soil actinomycetes. Aminoglycosides are bactericidal.

Mechanism of action : Cause misreading of m-RNA code and affect permeability. Other antibiotics which inhibit protein synthesis are only static.

Aminoglycosides

Diffuse across outer coat of gram-ve bacteria (e-

transport, O2 dependent, only aerobes)

Bind to 30s (streptomycin), 50s (others), 30s-50s interface. Protein synthesis initiation stopped.

Cause distortion of mRNA codon recognition. Misreading of mRNA code. Wrong amino acid enters the peptide chain.

Abnormality occur. Bacteria become more permeable and leak out ions, amino acids and protein.

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• Uses : Tuberculosis

Subacute bacterial endocarditis

pseudomonas, proteus or klebsiella infection

Meningitis caused by gram-ve bacteria

Neomycin is used topically for infected wounds, ulcers, burn, external ear infection, conjuctivitis, post operative infections.

Systemic

•Streptomycin

•Gentamycin

•Kanamycin

•Tobramycin

•Amikacin

Topical •Neomycin

•Framycetin

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3. MACROLIDES : Macrolides are the antibiotics having a macrocyclic lactone ring with attached sugar. They are bacteriostatic. Erythromycin is the first member discovered.

• Mechanism of action : Macrolides bind to 50s ribosome and interfere with translocation.

When peptide bond forms between amino acid & peptide chain at acceptor site (A).

The elongated chain is translocated back to peptidyl site (P).

Thus site (A) becomes available for next amino acyl-t-RNA attachment. This is called translocation.

Erythromycin binds to 50s ribosome and inhibit this translocation.

Thus protein synthesis inhibited.

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• Macrolides covers mostly gram+ve and a few gram-ve baterias.

Erythromycin is highly active against:

Str. Pyogenes

Str. Pneumaniae

N. gonorrhoeae

C. diphtheriae

Uses : severe campylobacter enteritis

pertusis

chlamydial infection

pneumonia, sinusitis, bronchitis

Brands : ALTHROCIN – ALEMBIC (erythromycin)

EROATE – LUPIN (erythromycin)

AZEE – CIPLA (azithromycin)

AZRO – PIRAMAL (azithromycin)

CELEX – GSK (clarithromycin)

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4. TETRACYCLINES: These are the antibiotics having a nucleus of four cyclic rings. They are obtained from soil actinomycetes. They are primarily bacteriostatic.

Mechanism of action :

• Tetracycline

• Oxytetracycline

• Doxycycline

• Domeclocycline

• Minocycline

• Uses:

Cocci : N. gonorrhoeae & N. meningitides

Bacilli : Gram+ve : Corynebateria, Propionibacterium acnes, B.anthracis

Gram-ve : V. cholera, Yersinia pestis , Helicobacter pylori

Binds to 30s ribosomes

Attachment of aminoacyl-t-RNA to the mRNA ribosome complex is interfered

Peptide chain fails to grow

protein synthesis inhibited

Bacteriostatic action.

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5. CHLORAMPHENICOL :Chloramphenicol was initially obtained from Streptomyces venezuelae.

Antibacterial spectrum:

It is primarily bacteriostatic. Active against gram+ve & gram-ve organisms same as tetracyclin.

Like tetracyclin it is inactive against Mycobacterium, Pseudomonas, many proteus, viruses and fungi.

Mechanism of action:

Chloramphenicol

binds to 50s ribosome

inhibit the transfer of elongated peptide chain to the newly attached aminoacyl -tRNA at ribosome mRNA complex.

Protein synthesis inhibited.

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• Uses:

Bacterial meningitis

Brain abscess

Gas gangrene : death & decay of wound tissues infected by soil bacterium Clostridium. Toxins produced cause tissue decay and generate gas.

Whipple’s disease : less absorption of digested food in intestine, occur in males.

Severe gastroenteritis

Plague

• Brands: CHLOREXIN CAP- CIPLA

DEXOREN- INDOCO

PERAXIN – PIRAMAL

CHLOROMYCETIN CAP- PFIZER

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6. GLYCOPEPTIDES :

It is active against MRSA. It is bactericidal to gram+ve cocci, Neisseria, clostridia and diphtheroids.

• Mechanism of action:

It inhibits the bacterial cell wall synthesis.

• Uses: Staphylococcal enterocolitis Septicemia, Osteomyelitis.

• Brands : VANCOGEN – ALKEM

VANLID – CIPLA

VANCORIN – EMCURE

vancomycin

binds to terminal dipeptide 'D-ala-Dala' sequence of peptidoglycan unit

prevents the assembly and cross linking of these units

cell wall not form

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7. OXAZOLIDINONE :

Linezolid : active against only gram+ve bacterias. It is primarily bacteriostatic.

• Mechanism of action:

It inhibits bacterial protein synthesis ta an early step and different site than other.

Linezolid

binds to 23s fraction of 50s ribosome

interfere with the formation of N-formylmethionine-tRNA-70s complex

thus tRNA binding site distorts

Protein synthesis not occur

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• Uses : uncomplicated skin and skin structure infection.

Community acquired pneumonia, Nocosomial pneumonia.

• Brands: ALZOLID – ALEMBIC

LIZOLID – GLENMARK

LINOSPAN – CIPLA

8. LINCOSAMIDE:

Clindamycin : it is similar in MOA to erythromycin (inhibit protein synthesis by binding to 50s ribosome).

• Uses : Acne, Bacterial vaginosis.

• Brands :

ACNESOL – SYSTOPIC

CLINDAC A – GALDERMA

CTOP – INTAS

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9. FLOROQUINOLONES:

They are quinolone antimicrobials.

• Norfloxacin

• Ciprofloxacin

• Ofloxacin

• Levofloxacin

• Moxifloxacin

Mechanism of action:

• FQs act by inhibiting the enzyme bacterial DNA gyrase.

• DNA gyrase consist of A and B subunits.

• A subunit cause nicking of strand, while B subunit introduce –ve supercoil into the strand, and then A subunit reseals the strand. This is necessary to prevent the excessive positive supercoiling of DNA strands, hence DNA replication occur.

• FQs bind to A subunit and interfere with the strand cutting and resealing function.

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Ofloxacin uses: Brands:

• Leprosy ALPROXEN- ALKEM

• Uncomplicated gonorrhoea EUFOX - LUPIN

OFLOMAC- MACLEODS

• UTI OFLOX - CIPLA

• Chronic bronchitis

• Traveller’s diarrhea

• LRTI

• Bacterial conjunctivitis

• Bacterial corneal ulcer

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10. OTHERS:

A. Mupirocin

B. Polypeptides

i. Polymyxin-B

ii. Colistin

iii. Bacitracin

• MUPIROCIN

• It is a novel antibiotic produced through fermentation of Pseudomonas fluorescens. It inhibits isoleucyl transfer-RNA synthetase and arrestbacterial protein synthesis.

• Uses: Primary skin infection- impetigo, folliculitis, furunculosis, ecthyma. Secondary skin infection- eczema, abrasion, lesions, insect bites, wounds, cuts. • Brands: BACTROBAN – GSK MPOWER- ZYDUS SUPIROCIN - GLENMARK

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Polymyxin-B & COLISTIN

• Active against only gram-ve bacteria. They are bactericidal. They cause distortion in bacterial cell membrane and cause pseudopore formation, so that ions, amino acids leak out. And bacteria dies.

• Uses: ocular, autic and skin infections.

• Brands: NEOSPORIN – GSK

CADIPRIM – CADILA

ORIPRIM – ZYDUS CADILA

BACITRACIN

Mostly active against gram+ve bacterias. Acts by inhibiting cell wall synthesis. Highly toxic so not given parenterally.

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Resistance to antibiotics:

Resistance of bacteria to the effects of antibiotics has become a major problem in the treatment of disease. Bacteria that are not killed or stopped by antibacterial drugs may change in form so that they resist attack against their cell walls or even produce enzymes that kill the antibiotics.

Types of Resistance:

Resistance: When any antibiotic does not show

affect against specific microbes then it means drug

resistance is developed.

Natural: some antibiotics are naturally resistant to specific

microbes.

Eg- Penicillin is resistant to gram-ve bacteria,

Tetracyclin is resistant to M. tuberculosis.

Acquired: microbes become resistant due to use of

antibiotics for a long period of time.

Eg- Sulfonamides are resistant to Gonococci

THANK YOU

A PRESENTATION BY SURYA PRAJAPAT