Tetracyclines

Tetracyclines - The Ribosome Wreckers

• Broad-spectrum, bacteriostatic antibiotics.
• MoA: Reversibly bind 30S ribosomal subunit, blocking aminoacyl-tRNA access to A-site. 📌 Buy AT 30.
• Key Drugs: Doxycycline, Minocycline (long-acting); Tetracycline (short-acting).
• Uses: Atypical pneumonias (Mycoplasma, Chlamydia), Rickettsia, Brucellosis, Cholera, Acne.
• AEs: GI distress, photosensitivity, teeth/bone issues (<8 yrs), Fanconi syndrome (expired).
• Contraindications: Pregnancy, breastfeeding, children <8 yrs.

⭐ Tetracyclines are bacteriostatic, binding reversibly to the 30S ribosomal subunit and thereby preventing the attachment of aminoacyl-tRNA. oka

Tetracyclines - Journey Through Body

• Oral Absorption:
  • Variable; food ↓ (not Doxy, Mino).
  • Chelation with Ca²⁺, Mg²⁺, Fe²⁺, Al³⁺ impairs absorption.

  ⭐ Avoid with dairy, antacids, iron supplements due to this chelation.

• Distribution:
  • Wide; CSF (Mino > Doxy).
  • Accumulates: liver, kidney, spleen, skin.
  • Binds calcified tissues (bone, teeth).
  • Crosses placenta, breast milk.
• Metabolism:
  • Most: minimal. Doxy/Mino some hepatic met.
• Excretion:
  • Tetracycline: Renal.
  • Doxycycline: GI/fecal (safe in renal failure).
  • Minocycline: Hepatic met., renal/fecal excretion.
  • Tigecycline: Biliary/fecal.

Tetracyclines - Bug Busters' Hit List

• Broad-spectrum: G+, G-, many anaerobes.
• Effective against:
  • Atypical bacteria: Mycoplasma pneumoniae, Chlamydia spp. (trachomatis, psittaci), Rickettsia spp.

    ⭐ Drug of choice for Rickettsial infections (e.g., Rocky Mountain Spotted Fever, Q fever), Chlamydial infections (e.g., LGV, psittacosis), and Mycoplasma pneumoniae.

  • Spirochetes: Borrelia burgdorferi (Lyme disease), Leptospira interrogans, Treponema pallidum (if penicillin-allergic).
  • Zoonotic diseases: Brucellosis (with aminoglycoside), Plague (Yersinia pestis), Tularemia (Francisella tularensis).
  • Vibrio cholerae.
  • Acne vulgaris (low-dose, anti-inflammatory).
  • Malaria: Prophylaxis & treatment (Doxycycline).
  • Part of H. pylori eradication regimens.
• 📌 Mnemonic for spectrum: VACUUM THe BedRoom.

Tetracyclines - The Nasty Side Effects

• Gastrointestinal: Nausea, vomiting, diarrhea, epigastric pain, esophageal ulceration.
• Bones & Teeth:
  • Permanent yellow-brown tooth discoloration, enamel hypoplasia.
  • Reversible bone growth inhibition in premature infants.

  ⭐ Contraindicated in pregnancy, breastfeeding, and children <8 years due to deposition in developing bones and teeth, causing permanent discoloration and enamel hypoplasia.

• Phototoxicity: Exaggerated sunburn reaction (esp. demeclocycline, doxycycline).
• Hepatotoxicity: ↑ risk in pregnancy (IV), pre-existing liver disease.
• Renal Toxicity: Fanconi-like syndrome (outdated); worsens azotemia (except doxycycline, minocycline).
• Vestibular Toxicity: Dizziness, vertigo, ataxia (minocycline).
• Other: Superinfections (Candida, C. difficile), benign intracranial hypertension (pseudotumor cerebri). oka

Tetracyclines - Resistance & Risky Mixes

• Resistance Mechanisms:
  • ↑ Efflux (e.g., TetA, TetK) - common
  • Ribosomal protection (e.g., TetM, TetO) - alters 30S
  • Enzymatic inactivation - less common
• Risky Drug Interactions: ⚠️
  • Cations ($Ca^{2+}$, $Mg^{2+}$, $Fe^{2+}$), Dairy: ↓ absorption (chelation)
  • Penicillins: Antagonistic effect
  • Oral Contraceptives: ↓ efficacy
  • Warfarin: ↑ anticoagulant effect
  • Retinoids (e.g., Isotretinoin): ↑ risk of pseudotumor cerebri

⭐ Tigecycline, a glycylcycline, overcomes major resistance mechanisms like efflux pumps and ribosomal protection proteins.

High‑Yield Points - ⚡ Biggest Takeaways

• Bacteriostatic; inhibit protein synthesis by binding 30S ribosomal subunit.
• Broad spectrum: atypicals (Mycoplasma, Chlamydia, Rickettsia), spirochetes.
• Oral absorption impaired by divalent/trivalent cations (milk, antacids, iron).
• AEs: Photosensitivity, GI distress, teeth discoloration & bone issues in children <8 yrs, Fanconi syndrome (outdated).
• Doxycycline: long-acting, fecal excretion (safer in renal impairment), DOC for Lyme disease, RMSF.
• Tigecycline: IV glycylcycline, active against MRSA, VRE.
• Contraindicated in pregnancy, breastfeeding, and children <8 years.