minocycline

**Mechanism of action** - Bacteriostatic. It binds the 30S ribosomal subunit and blocks attachment of aminoacyl-tRNA to the mRNA-ribosome complex (A site), which inhibits protein synthesis. - Tetracyclines enter bacterial cells through porins and an energy-dependent active transport system. - Resistance comes mainly from efflux pumps (plasmid-encoded) and ribosomal protection proteins. Minocycline and doxycycline are less affected by efflux than tetracycline, and tigecycline (a glycylcycline) evades both mechanisms.

**Pharmacokinetics** - It is highly lipophilic, so it is well absorbed orally (about 90-100%) and penetrates tissues and the CNS well. It reaches the prostate, sebaceous glands, and the CSF, and it can eradicate the meningococcal carrier state. - Absorption is impaired by divalent and trivalent cations (Ca²⁺, Mg²⁺, Fe²⁺/Fe³⁺, Al³⁺), so avoid taking it with dairy, antacids, or iron. Absorption is affected less than with tetracycline. - Metabolism is largely hepatic, with a half-life of about 12-24 hours. It does not need dose adjustment in renal failure, unlike older tetracyclines. Doxycycline is also safe in renal failure because it is eliminated by the fecal route.

**Clinical uses** - Acne vulgaris (inhibits *Cutibacterium acnes* and has anti-inflammatory effects) and rosacea. - Community-associated MRSA skin and soft-tissue infections. - Rickettsial infections (Rocky Mountain spotted fever, typhus), *Chlamydia*, *Mycoplasma*, *Borrelia burgdorferi* (Lyme disease), *Vibrio cholerae*, *Ureaplasma*, *Nocardia*, and *Acinetobacter* (alternative). - Historically used for meningococcal carrier eradication, but rifampin, ciprofloxacin, and ceftriaxone are now preferred because of vestibular toxicity. - Adjunct for atypical mycobacteria and leprosy.

**Adverse effects (high-yield)** - **Vestibular toxicity:** dizziness, vertigo, ataxia, and nausea. This is more common with minocycline than with other tetracyclines. - **Teeth and bone:** tooth discoloration (yellow-brown), enamel hypoplasia, and impaired bone growth when given to children under 8 years old, during pregnancy, or while breastfeeding. Tetracyclines chelate calcium and deposit in developing teeth and bone. - **Photosensitivity:** less than with doxycycline, but present. - **Hyperpigmentation:** blue-gray discoloration of skin, nails, sclera, scars, and mucosa with prolonged use. This is more specific to minocycline. - **Autoimmune reactions:** drug-induced lupus (anti-histone antibodies), autoimmune hepatitis, and serum-sickness-like reactions. - **Other:** DRESS (drug reaction with eosinophilia and systemic symptoms), benign intracranial hypertension/pseudotumor cerebri (headache, papilledema; risk is higher with concurrent vitamin A/retinoids, so avoid combining with isotretinoin), GI upset, *Candida* overgrowth, and *C. difficile* colitis. - **Fanconi syndrome:** seen with expired (degraded) tetracyclines. This applies to the class and is not a specific feature of minocycline. - **Hepatotoxicity:** rare, with fatty liver reported mainly with IV tetracyclines in pregnancy.

**Contraindications and cautions** - Pregnancy (teratogenic effects on teeth and bone), children under 8 years old, and hypersensitivity. Monitor the liver if used long-term. - Avoid co-administration with isotretinoin because of the risk of pseudotumor cerebri.

**Comparison with doxycycline** | Feature | Minocycline | Doxycycline | |---|---|---| | CNS penetration | Excellent | Good | | Vestibular toxicity | Yes (prominent) | Rare | | Photosensitivity | Less | More | | Drug-induced lupus | Associated | Rare | | Hyperpigmentation | Associated | Rare | | Renal dosing | Generally not needed | Not needed |

**Board pearls** - "Tetracyclines: demeclocycline also causes nephrogenic DI" (used for SIADH). - "Teeth and bones, vertigo, and photosensitivity": minocycline is the one with dizziness and blue-gray pigmentation. - Mnemonic: "Tetra-cyclines: *Teeth* and *Tendons*" is not correct (fluoroquinolones affect tendons). Use "Teeth, Bones, Sunburn, Fanconi." - Tigecycline is a glycylcycline that is related structurally to minocycline and covers MRSA, VRE, and multidrug-resistant gram-negatives, but not *Pseudomonas*. - Minocycline is also under study for neuroprotective and anti-inflammatory effects, but this is not tested.