Tetracyclines

Key Examples

• Doxycycline
• Lymecycline

 

Common indications

• Acne vulgaris, particularly where there are inflamed papules, pustules and/or cysts (Proprionibacterium acnes).
• Lower respiratory tract infections including infective exacerbations of COPD (e.g. Haemophilus influenzae), pneumonia and atypical pneumonia (mycoplasma, Chlamydia psittaci, Coxiella burnetii [Q fever]).
• Chlamydial infection including pelvic inflammatory disease.
• Other infections such as typhoid, anthrax, malaria and Lyme disease (Borrelia burgdorferi).

 

Mechanisms of action

• Tetracyclines inhibit bacterial protein synthesis. They bind to the ribosomal 30S subunit found specifically in bacteria. This prevents binding of transfer RNA to messenger RNA, which prevents addition of new amino acids to growing polypeptide chains. Inhibition of protein synthesis is ‘bacteriostatic’ (stops bacterial growth), which assists the immune system in killing and removing bacteria from the body. Tetracyclines have a relatively broad spectrum of antibacterial activity.
• Tetracyclines were discovered in 1945 and have been widely used. Consequently, some bacteria have acquired resistance to these antibiotics. A common mechanism is through acquisition of an efflux pump, which allows bacteria to pump out tetracyclines, preventing cytoplasmic accumulation.

 

Important adverse effects

Like most antibiotics, tetracyclines commonly cause:

• Nausea 
• Vomiting 
• Diarrhoea 
• Clostridium difficile infection : They are considered to be among the lowest risk antibiotics for this (see Penicillins, broad-spectrum). 
• Hypersensitivity reactions: occur in ~1 people who take tetracyclines, including immediate and delayed (see Penicillins). As antibiotic structures are different, there is no cross-reactivity with penicillins or other β-lactam antibiotics.

Tetracycline-specific side effects include: 

• Oesophageal irritation, ulceration and dysphagia
• Photosensitivity (an exaggerated sunburn reaction when skin is exposed to light)
• Discolouration and/or hypoplasia of tooth enamel if prescribed for children. 
• Intracranial hypertension is a rare adverse effect causing headache and visual disturbance.

Warnings

• Tetracyclines bind to teeth and bones during fetal development, infancy and early childhood and so should not be prescribed during pregnancy, breastfeeding or for children ≤12 years of age. They should be avoided in people with renal impairment as their anti-anabolic effects can raise plasma urea and reduced excretion can increase the risk of adverse effects.

Important interactions

• Tetracyclines bind to divalent cations. They should therefore not be given within 2 hours of calcium, antacids or iron, which will prevent antibiotic absorption. Tetracyclines can enhance the anticoagulant effect of warfarin by killing normal gut flora that synthesise vitamin K.