Tetracyclines
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Direct answer
Tetracyclines — tetracycline, doxycycline, minocycline and the glycylcycline tigecycline — are broad-spectrum bacteriostatic antibiotics that bind the 30S ribosomal subunit and block attachment of aminoacyl transfer RNA. Doxycycline is the workhorse for rickettsiae, chlamydiae, cholera, scrub typhus and acne, and is the safest tetracycline in renal impairment because it is excreted in bile. Chelation with calcium and iron plus tooth discolouration in the young restrict their use.
What you must remember
- Mechanism: bind the 30S subunit, prevent aminoacyl-tRNA docking at the acceptor site; bacteriostatic, so they antagonise bactericidal beta-lactams in meningitis-type infections.
- Absorption is impaired by milk, antacids, iron, zinc and calcium through chelation — space doses by two hours; doxycycline and minocycline are more completely absorbed and less affected by food.
- Elimination separates the class: tetracycline is renally cleared and accumulates in renal failure; doxycycline is excreted in faeces via bile and is the member of choice when the creatinine clearance is low.
- Classical indications: rickettsial fever and scrub typhus (doxycycline is drug of choice), cholera single-dose doxycycline, brucellosis with rifampicin or streptomycin, chlamydial infection, Lyme disease, acne vulgaris low-dose courses, rosacea, melioidosis and malaria prophylaxis.
- Tooth and bone toxicity: deposition in forming enamel and dentine causes grey-brown discolouration — contraindicated in pregnancy after the early weeks, in breastfeeding mothers and in children under eight years.
- Photosensitivity is prominent with doxycycline and demeclocycline; oesophageal ulceration is prevented by swallowing with a full glass of water sitting upright; minocycline causes vestibular dysfunction and skin pigmentation.
- Tigecycline, a glycylcycline, evades common efflux resistance and covers MRSA, vancomycin-resistant enterococci and anaerobes but not Pseudomonas; regulatory guidance notes excess mortality in some trials, restricting it to situations without alternatives.
Common confusion
Two members are endlessly swapped: doxycycline is renally safe, highly lipophilic and phototoxic, whereas plain tetracycline accumulates in renal impairment — the reverse of what intuition suggests about "older versus newer". Candidates also forget why milk ruins therapy: the drug itself fails, not the patient, because calcium chelates it into a non-absorbable complex.
Exam-focused takeaway
Theory answers should give the 30S mechanism, chelation pharmacokinetics, the infection list where tetracyclines are drug of choice, and tooth, bone and skin toxicities. Viva examiners ask why doxycycline suits renal failure and leptospirosis alternatives. MCQs test rickettsiae and cholera indications, the under-eight contraindication, milk-antacid interactions, oesophageal ulceration, minocycline vestibular effects and tigecycline's absent pseudomonal cover.
Frequently asked questions
Why should tetracyclines not be taken with milk or antacids?
Divalent cations such as calcium, magnesium, aluminium and iron chelate tetracyclines in the gut, forming complexes that are not absorbed.
Which tetracycline is safe in renal impairment?
Doxycycline, because it is eliminated mainly in faeces via biliary excretion rather than by the kidney.
Why are tetracyclines avoided in children and pregnancy?
They bind developing tooth enamel and bone, producing discolouration and dental hypoplasia; the risk extends to the fetus and the nursing infant.
Which infections mandate doxycycline as first line?
Scrub typhus and other rickettsial fevers, cholera in adults, chlamydial genital infection and mild melioidosis, with acne and rosacea as common elective uses.
How does tigecycline differ from classical tetracyclines?
Its glycyl side chain defeats efflux pumps and ribosomal protection, restoring activity against MRSA and resistant gram-negatives, though Pseudomonas remains inherently resistant.