Tetracyclines and chloramphenicol are broad-spectrum antibiotics that act by inhibiting bacterial protein synthesis. Because they act on bacterial ribosomes (which differ from human ribosomes), they can selectively stop bacterial growth without harming human cells. Despite being older drugs, they continue to play an important role in treating specific infections.
TETRACYCLINES
Tetracyclines are a group of antibiotics derived originally from Streptomyces species. They are known for their broad spectrum of activity against gram-positive bacteria, gram-negative bacteria, atypical organisms, rickettsiae, and protozoa.
Common Tetracyclines
- Tetracycline
- Doxycycline
- Minocycline
- Tigecycline (a glycylcycline derived from tetracyclines)
Mechanism of Action
Tetracyclines enter bacterial cells and bind to the 30S ribosomal subunit, blocking the attachment of tRNA. This prevents bacteria from making proteins, stopping their growth.
Spectrum of Activity
- Gram-positive and gram-negative bacteria
- Rickettsiae (typhus, Rocky Mountain spotted fever)
- Chlamydia
- Mycoplasma
- Vibrio cholerae
- Brucella
- H. pylori (in combination therapy)
Uses
- Acne (doxycycline, minocycline)
- Respiratory infections caused by atypical organisms
- Sexually transmitted infections like chlamydia
- Rickettsial infections
- Cholera
- Plague, tularemia (alternative therapy)
- H. pylori eradication (as part of combination therapy)
Pharmacokinetics
- Absorption decreases with milk, antacids, and iron supplements
- Doxycycline and minocycline are well absorbed and widely used
- Tetracyclines concentrate in bone and teeth
- Excreted mainly in urine except doxycycline (bile)
Adverse Effects
- Teeth discoloration (yellow-brown) in children
- Delayed bone growth in children
- Photosensitivity
- Nausea, vomiting, diarrhoea
- Hepatotoxicity (especially in pregnancy)
Contraindications
- Children under 8 years
- Pregnancy and breastfeeding
- Severe liver disease
CHLORAMPHENICOL
Chloramphenicol is a potent broad-spectrum antibiotic that acts on the bacterial ribosome. Due to its serious side effects, it is reserved for severe infections where safer drugs cannot be used.
Mechanism of Action
Chloramphenicol binds to the 50S ribosomal subunit and inhibits the enzyme peptidyl transferase. This blocks protein chain elongation and stops bacterial growth.
Spectrum of Activity
- Gram-positive and gram-negative bacteria
- Anaerobes
- Rickettsiae
- H. influenzae
- N. meningitidis
Uses
Due to toxicity, chloramphenicol is used only when safer alternatives are not effective:
- Meningitis (especially in penicillin-allergic patients)
- Typhoid fever (alternative option)
- Rickettsial infections (when tetracyclines cannot be used)
- Serious anaerobic infections
Pharmacokinetics
- Well absorbed orally
- Reaches high levels in cerebrospinal fluid (CSF)
- Metabolized in liver (glucuronidation)
- Excreted through urine
Adverse Effects
- Aplastic anemia (rare but fatal; main reason for restricted use)
- Bone marrow suppression – reversible at moderate doses
- Gray baby syndrome in newborns (due to immature liver enzymes)
- Nausea, vomiting, diarrhoea
Gray Baby Syndrome
Occurs in newborn babies who cannot metabolize the drug properly. Symptoms include vomiting, loose stools, low blood pressure, and grey-colored skin. Can be fatal if untreated.
Drug Interactions
- Inhibits cytochrome P450 enzymes → increases toxicity of warfarin, phenytoin
- Should not be combined with bone marrow suppressing drugs
Resistance
- Drug inactivation by enzymes (chloramphenicol acetyltransferase)
- Altered ribosomal binding sites
- Decreased drug uptake by bacteria
Detailed Notes:
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