Chemistry and Pharmacodynamics
- Contain a linear, fused 4-ring nucleus
- Have a variety of attached functional groups
Mechanism of action
- Tetracyclines bind reversibly to the 30S ribosomal subunit:
- Block the attachment of aminoacyl-tRNA to the mRNA–ribosome complex
- Disrupt bacterial protein synthesis
- Bacteriostatic (inhibit but do not kill organisms)
- Demeclocycline is an antidiuretic hormone (ADH) antagonist at the renal tubule as well.
- Oral dosage forms well absorbed
- Absorption is decreased within 1–2 hours after consumption of dairy products, antacids, and any other products containing iron, magnesium, calcium, or aluminum (e.g., supplements, vitamins), as these elements can bind with tetracyclines and reduce their ability to be absorbed.
- Adequately distributed in body fluid
- Poor CSF penetration except for minocycline
- Minocycline is most lipophilic → achieves therapeutic CSF levels
- Minocycline distribution ↑ in saliva and tears
- Doxycycline distribution ↑ in prostatic fluids
- Metabolism: The majority of 1st-generation tetracyclines are not metabolized.
- Primarily renal excretion
- Doxycycline excreted via bile/feces
|Off-label use: part of multidrug treatment for Helicobacter pylori (peptic ulcer disease)|
|Doxycycline||Tetracycline indications, plus:|
|Minocycline||Tetracycline indications, plus:|
(injection solution (IV))
Adverse Effects and Contraindications
- GI upset:
- Nausea and vomiting most common side effects
- Advise patients to consume medication with water and sit upright for 30 minutes after ingestion to prevent esophagitis.
- Photosensitivity of the skin:
- Chemical interaction between drug/metabolite in the skin and UV rays may cause a severe sunburn-like reaction.
- Advise patients to avoid direct sunlight and artificial UV rays (i.e., tanning beds) and wear protective clothing and sunscreen.
- ↓ Bone growth: children < 8 years old
- Tooth yellowing and enamel hypoplasia: typically in children < 8 years old
- Vestibular dysfunction with minocycline or doxycycline
- Drug-induced lupus-like reaction with minocycline
- Fanconi syndrome with expired tetracyclines
- Pregnancy (category D):
- May cause congenital defects, hepatotoxicity in the mother, and abnormal tooth development as above
- The exception is doxycycline for treatment of Rickettsia spp.
- Children < 8 years old except for doxycycline for treatment of Rickettsia spp.
- Renal failure except with doxycycline because of its GI elimination
- Present in breast milk in small amounts
- Avoid prolonged or repeated courses.
- Short-term use acceptable
- Previous theoretical concern for staining of infants; teeth and possible bone deposition inhibiting growth, but recent research suggests these are unlikely
- Preexisting liver disease/failure: High doses may lead to liver toxicity.
- Drug–drug interactions:
- Anticonvulsants: decrease tetracycline effectiveness and alter anticonvulsant drug levels
- Warfarin: ↑ INR
- Oral contraceptives: decreased effectiveness
- Black box warning for tigecycline: associated with ↑ mortality
Mechanisms of Resistance
- Development of plasma-mediated efflux pumps for active ejection, limiting ability of the drug to accumulate in cells
- Decreased cell-wall penetration
- Ribosomal protection proteins prevent binding.
- Enzymatic destruction
Comparison of Medications
|Minocycline||Like tetracycline, plus:|
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