1 protein synthesis inhibitors. 2 these antibiotics exert their actions by targeting the bacterial...

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PROTEIN SYNTHESIS INHIBITORS

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• These antibiotics exert their actions by targeting the bacterial ribosome which has components that differ structurally from mammalian cytoplasmic ribosome.

• Bacterial ribosome is smaller 70 s as compared to the mammalian cytoplasmic ribosome - 80 s

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Very broad spectrum.

Aerobic gm +/-

Many anaerobes

SE: Toxicity

Nephro-

Oto-toxic

Very broad spectrum.

Many gm +, some gm –

Pen allergic pt

SE: GI distress

Gm+/- bacteria

Spirochetes, Rickettsiae

Resistant organisms

SE: GI distress

Photosensitivity

Impair teeth & bone growth

Chloramphenicol: many Gm -/+ bacteria Serious infxn. SE: Bone marrow aplasia

Clindamycin: Most Gm +, some Gm – Alternative use. SE: colitis - PMC (C. difficile)

Ethionamide: TB

SE: GI distress

Azithromycin (Zithromax)

p. 554

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Aminoglycosides

• Susceptible organisms allow aminoglycosides to diffuse through their porin channels in their outer membranes. These organisms have oxygen dependant system that transports the drug across cell membrane.

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• They bind to the 30s ribosomal subunit interfering with the assembly of functional ribosomal apparatus.

• They synergise with beta lactAM ANTIBIOTICS BECAUSE OF THE LATTERS ACTION ON CELL WALL SYNTHESIS, WHICH ENHANCES DIFFUSION OF THE AMINOGLYCOSIDES INTO THE BACTERIUM.

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• THEY ARE BACTERICIDAL.• THAY ARE EFFECTIVE ONLY AGAINST

AEROBIC ORGANISM, AS ANEROBES LACK THE OXYGEN REQUIRING TRANSPORT SYSTEM.

• STREPTOMYCIN IS USED TO TREAT TB, PLAGUE & TULAREMIA.

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• Resistance• Porin channels are absent• Altered 30 s subunit• Plasmid associated synthesis of enzymes

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Aminoglycosides

Route : parenteral• Exception : neomycin –topical and sometimes

oral for hepatic coma.• Distribution : low conc. in CSF,• Crosses placenta• Excretion : Glomerular filtration• HIGH CONCENTRATIONS ACCUMULATE IN THE

RENAL CORTEX, ENDOLYMPH AND PERILYMPH OF INNER EAR.

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Aminoglycosides - SE

• OTO TOXICITY• DEAFNESS, VERTIGO

• NEPHRO – TOXICITY• RENAL TUBULAR NECROSIS

• NEURO MUSCULAR PARALYSIS- Ach• RX – mostly calcium gluconate or neostigmine

can reverse the situation• CONTACT DERMATITIS –neomycin

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TETRACYCLINES

• Consist of 4 fused rings with a system of conjugated double bonds.

• THEY BIND TO THE 30S SUBUNIT OF THE BACTERIAL RIBOSOME AND BLOCK ACCESS OF THE AMINO ACYL-TRNA TO THE MRNA-RIBOSOME COMPLEX. THUS THEY INHIBIT BACTERIAL PROTEIN SYNTHESIS.

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TETRA CYCLINES• ROUTE : ORAL ,DECREASED BY

• MILK• ANTACIDS• IRON SUPPLEMENTS

• DISTRIBUTION :CROSSES BBB but not that good. Minocycline readily crosses placenta.

• High levels in calcium tissues- bones, teeth, some tumors

• Excretion :renal , exception – doxycycline ( In bile )

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• They are useful in the treatment of chlamydial infection, rocky mountain spotted fever, lyme disease, mycoplasma pneumonia , cholera.

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TETRA CYCLINES - SE

• MC : GIT- epigastric discomfort• CALCIUM DEPOSITION : GROWTH –STUNTED,

TEETH – SMALL, DISCOLORED• PHOTO TOXICITY• HEPATO TOXICITY• VERTIGO – MINOCYCLINE• ICT –INCREASED• CI : WOMEN – preg, lactating, children

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Macrolides

Macrolides are a group of antibiotics with a macrocyclic lactone structure to which one or more deoxy sugars are attached.

Macrolides bind to 50 s subunit of the bacterial ribosome thus inhibiting the translocation steps of protein synthesis.

Erythromycin• Same like penicillin G• Indication – used in pt. with allergy to penicillins

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Clarithromycin• Spectrum : Erythromycin - Haemophilus

INFLUENZA

Azithromycin• Spectrum : Clarithromycin - Moraxella &

respiratory pneumonias

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Macrolides

• Route : oral• IV – thrombo phlebitis• Distribution : CSF – poor.• Prostate – good• Excretion : liver ( in bile)• Exception – clarithromycin – renal also

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Macrolides - SE

• MC : GIT• OTO TOXICITY• CHOLESTATIC JAUNDICE• CI : LIVER FAILURE

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chloramphenicol

• BINDS TO THE 50 S RIBOSOMAL SUBUNIT AND INHIBITS PROTEIN SYNTHESIS AT THE PEPTIDYL TRANSFERASE REACTION.

• RESISTANCE IS BECAUSE OF R FACTOR WHICH CODES FOR ACETYL CO-A

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• Broad spectrum antibiotic• Active against rickettsiae• Excellent against anaerobes• Can be bactericidal or bacteriostatic.

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CHLORAMPHENICOL

• ROUTE : ORAL / IV• DISTRIBUTION : CROSSES BBB, WITHOUT

INFLAMMATION• EXCRETION : RENALSE • GRAY BABY SYNDROME- under developed renal

function. Accumulation leads to interference with function of mitochondrial ribosomes.

• HEMOLYTIC ANEMIA : G 6 PD DEFICIENCY

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CLINDAMYCIN

INDICATION• BACTERIODES FRAGILIS• ROUTE : ORAL• EXCRETION : RENAL & HEPATIC• SE : PSEUDOMEMBRANOUS COLITIS

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• Quinipristin/dalfopristin• Mixture of two streptogramins in a ratio of 30

to 70.• Each component of this combination binds

to a separate site on 50 s bacterial ribosome. the combination drug is bactericidal.

• Active against mrsa resistant to vancomycin.

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• Linezolid• Methicillin and vancomycin resistant

staphylococcus aureus.• Inhibits formation of 70 s initiation complex

and thus inhibits protein synthesis.