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• Semisynthetic occurring:
– Doxycycline, minocycline, tigecycline,
lymecycline, methacycline and rolitetracycline
Available drugs - characters
• Tetracycline, oxytetracycline, demeclocycline
– Lower potency (250-500 mg tid)
– Orally given, short acting (t1/2 – 6-8 Hrs)
– Incompletely absorbed from stomach (60-80%)
– Primarily excreted through the kidneys
• Minocycline, doxycycline, tigecycline
– Higher potency (100 - 200 mg)
– Lipid soluble, long acting (t1/2 – 18-24 Hrs)
– Completely absorbed from stomach (95-100%)
– Excreted through liver
Tetracyclines - MOA
• Inhibition of Bacterial Protein Synthesis by
binding to 30S ribosomes – aminoacyl-t-RNA
to mRNA-ribosome complex – interfered
• Why do not affect host cells ? – transport and
sensitivity
Tetracyclines - MOA
Inhibition of Bacterial Protein Synthesis
Resistance
• Develops slowly in graded manner
• Tetracycline concentrating mechanism lessens
• Efflux pump
• Plasmid mediated synthesis of “protection
protein”
• Tetracycline inactivating enzyme
Cross resistance
Tetracyclines – Antimicrobial spectrum
• Bacteriostatic drugs: originally all types of organisms
except viruses and fungi – Both, gm+ve and gm-ve
bacteria, Rickettsiae, Chlamydia, Mycoplasma,
actinomycetes and some protozo
• Cocci: All +ve and –ve cocci
– S. pneumoniae, gonococi, meningitidis are sensitive.
Resistance developed to Staph aureus, pyrogens and
enterococci
• Bacilli (+ve): clostridia, listeria, anthracis etc, but not
Mycobacteria
• Enterobacteriocae: resistant and not effective -
pseudomonas, klebsiella and salmonella
Tetracyclines - Kinetics
• Older ones less absorbed – 60-80% (food interferes) but doxy and
mino – completely
• Chelating property – milk, antacids and iron preparations
• Distribution: wide and variable protein binding (different members)
– Concentrated in liver, spleen and bone & teeth – minocycline in fats
– Good CSF penetration 1/4th of plasma) – no relation with inflammation
• Excretion: Primarily in urine (dose adjustment in renal failure)
– Doxycycline is exception (bile)
• Preparations: Oral capsules, ½ to 2 Hrs pre and post food
– No IM: painful (oxy and tetra available)
– Also cream, ointment and ocular etc. preparations – high risk of
sensitization
Adverse Effects
GI disturbances: Due to Irritation
• Mild nausea and diarrhoea to severe, possibly life-threatening
colitis and Oesophageal ulcer etc.
Streptomyces venezuelae
Chloramphenicol
(streptomyces venezuelae)
• A natural product
(contains a nitrobenzene
moiety)
• Now all are synthetic
products
• Yellowish white crystalline
solid
• Stable aqueous solution
• Nitrobenzene –
antibacterial activity
Chloramphenicol - MOA
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