Tetracyclines

Tetracyclines: Introduction

Tetracyclines are a class of broad-spectrum antibiotics that are effective against a wide range of Gram-positive and Gram-negative bacteria, as well as atypical pathogens, rickettsiae, and some protozoa. They are bacteriostatic, meaning they inhibit bacterial growth rather than directly killing bacteria.

History

• Tetracyclines were first discovered in the 1940s from Streptomyces species.

• The development of semi-synthetic derivatives like doxycycline and minocycline improved absorption, tissue penetration, and side effect profiles.

Mechanism of Action

• Tetracyclines bind to the 30S subunit of bacterial ribosomes, blocking the attachment of tRNA to the mRNA-ribosome complex.

• This prevents protein synthesis, inhibiting bacterial growth.

• They are generally bacteriostatic, allowing the immune system to clear the infection.

Spectrum of Activity

• Gram-positive bacteria: Streptococcus, Staphylococcus (some strains)

• Gram-negative bacteria: E. coli, Haemophilus influenzae, Neisseria species

• Atypical bacteria: Mycoplasma, Chlamydia, Rickettsia, Legionella

• Other pathogens: Some protozoa like Plasmodium species

Common Uses

• Respiratory tract infections: Mycoplasma pneumonia, Chlamydial infections

• Sexually transmitted infections: Chlamydia, syphilis (alternative in penicillin-allergic patients)

• Rickettsial infections: Typhus, Rocky Mountain spotted fever

• Acne and skin infections: Long-term low-dose therapy

• Malaria prophylaxis and treatment (doxycycline)

Advantages

• Broad-spectrum coverage including atypical pathogens

• Good oral absorption and tissue penetration (especially doxycycline and minocycline)

• Can be used as an alternative for patients allergic to penicillin

Risks and Concerns

• Gastrointestinal disturbances: Nausea, vomiting, diarrhea

• Photosensitivity: Increased risk of sunburn

• Dental and bone effects: Can cause permanent tooth discoloration and affect bone growth in children under 8

• Liver toxicity: Rare, especially in high doses or pregnancy

• Drug interactions: Reduced absorption with calcium, magnesium, iron, or antacids

Examples of Tetracyclines

• Tetracycline – first-generation, oral, broad-spectrum

• Doxycycline – improved absorption, long half-life, widely used

• Minocycline – better tissue penetration, used in acne and certain infections

• Tigecycline – a glycylcycline derivative, active against resistant bacteria including MRSA