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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.