Antibiotics

ANTIBIOTICS

Yogapriya.vB.Opt(IIIyr)

SULFONAMIDES

Mechanism of action• Sulfonamide are bacteriostatic• These agents cause competitive inhibition of bacterial folate

synthetase,an enzyme needed for incorporation of p-aminobenzoic acid(PABA)into folic acid,a vital compound needed for bacterial growth

• Besides,it is also believed that sulfonamides,due to their structural similarity to PABA are taken up by mistake and there is no formation of altered folate which is metabolically injurious to the organisms concerned

CHEMICAL STRUCTURE OF PABA AND SULFANILAMIDE

Adverse effect• GI irritation like nausea,vomiting,anorexia,epigastric discomfort• Renal toxicities like crystalluria,haematuria• Hepatitis• Precipitation of kernicterus• Transient myopia

Drug interaction• Sulfonamides enchance the action of

warfarin,tolbutamide,phenytoin..etc by inhibiting their metsbolism• It may increase the chances of toxicity• It may counteract the efiiciency of gentamycin

QUINOLONES

• Quinolones are synthetic chemical compound• The parent compound is nalidixic acid• It is a weak antimicrobial substances• Some newer quinolonic substances,fluoroquinolones have been

developed by introducing one or more fluorine substituents• These are powerful antimicrobial substances

CLASSIFICATION OF FLUOROQUINOLONES

1ST GENERATION One fluoro substitutioneg: ciprofloxacin,norfloxacin,ofloxacin,pefloxacin

2ND GENERATION Additional fluoro and other substituentsThese drugs have extended spectrum of activityEg:sparfloxacin,gatifloxacin,fomefloxacin

Mechanism of actionAll fluoroquinolones exhibit anti-DNA gyrase activityWhile multiplying,the bacteria needs DNA gyrase for division,coiling and supercoiling of its DNA molecules• Topoisomerase II is the homologous enzyme in mammalian cell

which has a very low affinity for fluoroquinolones and so the toxicity to host cell is minimum

• Chromosomal mutation which produces a special type of DNA gyrase which has low affinity for fluoroquinolones

• Permeability to the drug is reduced

Adverse effects• GI irritation• Hemolytic anemia• Tendonitis• Convulsion• Hypersensitive reaction

Contraindication• Since fluoroquinolones may cause damage to the cartilage of juvenile

weight bearing bones• So these should not be used in children• These should also be avoided in pregnancy and lactation

Drug interaction• Antacid reduces their absorption• H2 blockers reduce their absorption• There is increased susceptibility of convulsion when quinolones are

used along with NSAID• Ciprofloxacin by reducing the metabolism of theophyllinees may

produce toxicity• Nalidixic acid and nitrofurantoins are antagonistic

BETA LACTAM ANTIBIOTIC

PENICILLIN• Penicillin nucleus consist of two rings- thiazolidine and beta

lactam,which are fused together,to this nucleus,side chains are attached by an amide linkage

Mechanism of action• Beta lactam antibiotic cause damage to the bacterial cell wall• Hence they are basically bacteriocidal agent• They inhibit two important enzymes, transpeptidase and

carboxypeptidase which are responsible for the synthesis of peptidoglycan

• As a result rapid lysis of the cell occurs• This lysis is augumented by activation of autolysins

Ocular penetration• Ocular penetration of various penicillin compound is poor• 0,5 to 1 million units of penicillin G given subconjunctivally produce

effective therapeutic level in aqueous humour and vitreous• Probenecid also retard the pumping effect of retinal pigment

epithelium

Adverse effect• Penicillin shock• Hypersensitive reaction• Bone marrow depression• Encephalopathy• Spinal cord damage

Drug interaction• Aminoglycoside should not be mixed with the penicillin in the same

drip• anticoagulant+large IV dose of penicillin;chances of bleeding as

bleeding time is prolonged • Parenteral penicillin+heparin=there is increased chance of bleeding• Tetracycline may hamper the bacteriocidal effect of penicillins• Probenicid increases the haif life of penicillins

CEPHALOSPORINS• They are semi-synthetic antibiotic obtained from a fungus

cephalosporium and they possess a beta lactam ring• They are bactericidal in nature and cause damage to bacterial

cellwall• However,their mechanism of action is alittle different from that of

penicillins

Orally active compound• 1st generation=cephalexin,cephradine,cephadroxil• 2nd generation=cefuroxime axetil,cefaclor• 3rd generation=cefixime

Adverse reaction• Hypersensitive reaction• Diarrhoea• Renal toxicity• Neutropenia and thrombocytopenia• Thrombophlebitis

Drug interaction• Chloramphenicol antagonizes the action of cephalosporins like

ceftazidime• Concurrent use of cephalosporin with aminoglycoside may produce

nephrotoxicity• It potentiate the hypoprothrombinaemic effect of anticoagulants

MONOBACTAM• In this group of antibiotic only beta lactam ring is present and the

second ring is missing• Aztreonam is the classical drug in this group

CARBAPENEMS• Imipenem is the most popular drug in this group• It is very potent.beta lactamase resistant• It is the broad spectrum beta lactam antibiotic

CHLORAMPHENICOL

• Originally it is derived from strepmyces venezuelae• It is totally synthetically produced for commercial purposes

Mechanism of action• It is mainly bacteriostatic in nature• It gets bound to 50S ribosomal subunitand there by inhibit

bacterial protein synthesis• Binding of aminoacyl-t-RNA to 50S ribosomal subunit is

prevented by it and thus peptide bond formation is ultimately hampered

Dosage• In ophthalmology 0.4%-0.5% solution and 1% eye ointment

usually used for topically use

Adverse effect• Bone marrow depression • GI irritation• Gray baby syndrome

TETRACYCLINES• Tetracyclines are agroup of broad spectrum antibiotic• Effective against wide variety of bacteria• The first drug of tetracycline family is chlortetracycline was

introduced in 1948• All members of this group are associated from soil

actinomycetes

Mechanism of action • Tetracycline is bacteriostatic• They get bound to 30S ribosomes of the susceptible organisms• And so the attachment of the aminocyl-t-RNA to m-RNA

ribosome complex is hampered leading to failure of the development of peptide chain

• Thus the protein synthesis is inhibited

Adverse effect• It possess Chelating property• Anterior dentition is affected• Inhibition of bone growth• Hepatic damage• Phototoxicity• Kidney toxicity• superinfection

MACROLIDS• All macrolid antibiotic posses a large lactone ring in their chemical

structure• Important member of this group are

erythromycin,clarithromycin,spiramycin

Mechanism of action• All macrolids inhibit protein synthesis in bacteria by binding to 50S

ribosomal subunit

Adverse effect• GI tract irritation can occur• Hearing impairment• Hypertensive reaction• Anaphylaxis• Steven Johnson syndrome

AMINOGLYCOSIDE

These are group of antibiotic obtained from soil actinomycetes The first among this group to be discovered was streptomycin

obtained from Streptomyces griseus Chemically all members of this grup consist of two or more amino

sugar linked glycosidically to a hexose nucleus

Mechanism of action Carriage of aminoglycoside across the bacterial cell membrane:this

process requires two condition (1)oxygen supply(2)alkaline ph Formation of wrong peptide chain due to distortion of mRNA codonsAminoglycoside streptomycin bound to 30S ribosomes where as others may get bound to 50S ribosomes and 30S-50S interface

Side effects Ototoxicity Renal toxicity neuromuscular blockade

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