Adverse Effects Of Tetracyclines  

Tetracycline group of drugs include tetracycline, chlortetracycline, methacycline, demeclocycline, doxycycline, lymecycline, minocycline and oxytetracycline.  

All of them are bacteriostatic drugs with a similar spectrum of activity. Currently, one of the important indications for the use of tetracyclines is typhus fevers caused by Rickettsiae (group of bacterial diseases spread to humans by fleas, lice, and jiggers). Doxycycline is the drug of choice for this indication.  

The group has similar adverse events, but the severity may be more with some members. For example, demeclocycline use has significant risk of photosensitivity reactions and nephrogenic diabetes insipidus.  

Tetracyclines, except minocycline and doxycycline are excreted unchanged in urine, and to a lesser extent, in bile. Thus, impaired renal function can increase their elimination half-life and drug accumulation to toxic levels. The dosage should, therefore, be adjusted in the presence of impaired renal function.  

Acute toxicity of tetracycline is relatively low. Therefore, severe toxicity following overdose is unlikely. However, a number of adverse drug reactions have been associated with both short term and long-term use of tetracyclines.  

The most frequent adverse reactions to tetracyclines are dose-related GI effects including nausea, vomiting, diarrhea, epigastric burning and ulceration. Tetrecyclin induced pancreatitis has also been described. 

Diarrhea resulting from irritation of tetracyclines should be promptly distinguished from that which results from pseudomembranous colitis, a potentially life-threatening complication.  

Tetracyclines are not recommended for treatment in infants and children younger than 8 years of age because their use has been strongly associated with permanent teeth discoloration, enamel hypoplasia, and a decrease in linear skeletal growth probably. This has been attributed to their chelating property and the formation of a tetracycline–calcium orthophosphate complex that deposits in the skeleton tissues. However, these drugs may be used in younger children only when other drugs are likely to be ineffective and when benefits clearly outweigh risks.   

Tetracyclines may cause increased intracranial pressure with papilledema & retinal hemorrhages, bulging of fontanels which are observed more frequently in children & infants than in adults, even when given in the usual therapeutic doses. The pressure returns to normal when drug is discontinued.   

Young women given tetracycline and vitamin A in combination for acne may be at special risk  for increased intracranial pressure and should be kept under surveillance.  

Tetracyclines administered orally or parenterally may lead to development of vaginal, oral, and even systemic superinfections caused by bacteria or fungi resistant to tetracyclins. Severe pseudomembranous colitis can also occur. They tend to occur most often in individuals with immunosuppresive disorders such as diabetes, leukemia, systemic lupus erythematosus especially if steroids are being administered.  

Tetracycline-induced hepatotoxicity is usually seen as a fatty degeneration of the liver resulting from inhibition of mitochondrial β-oxidation of fats. Jaundice appears first, and azotemia, acidosis, and irreversible shock may follow. Doxycycline and minocycline are safer than the others in this group.   

Hepatotoxicity is more likely to occur in pregnant women, in patients receiving high-dose intravenous therapy, and in patients with renal function impairment.  

Hypersensitivity reactions can develop with therapy in the form of various skin reactions along with more severe reactions including angioedema and anaphylaxis. other effects of hypersensitivity include cheilosis, atrophic or hypertrophic glossitis, pruritus ani or vulvae & vaginitis. Cross-sensitization among the various tetracyclines is common.  

Long term minocycline use (as in treatment of acne) can induce reversible lupus and severe autoimmune liver damage, brownish discoloration of skin, vestibular toxicity (dizziness, ataxia, nausea, and vomiting).  

Tetracyclines, particularly demeclocycline, may cause nephrotoxicity with polyuria, glucosuria, and aminoaciduria (Fanconi syndrome). These toxic effects have also been observed in patients ingesting expired and degraded tetracycline.  

Renal dysfunction, including elevated BUN, may occur due to the antianabolic activity of tetracyclines.   

Teracyclins, except minocycline, have been linked to hematologic aberrations; IgG antibody mediated intravascular hemolysis with hemoglobinemia, hemoglobinuria, thrombocytopenia, hypofibrinogenemia. 

Their long-term therapy may produce leukocytosis, atypical lymphocytes, toxic granulation of granulocytes, and thrombocytopenic purpura.  

Moreover, tetracyclines have been found to impair blood coagulation through decreased prothrombin activity & an impairment in rate of thromboplastin regeneration.  

Short-term use of tetracycline is acceptable in nursing mothers because milk levels are low and absorption by the infant is inhibited by the calcium in breast milk  

  Treatment  

  • Treatment is symptomatic and supportive  
  • Tetracycline and doxycycline have been implicated in causing esophageal ulcerations when taken therapeutically with minimal amounts of fluids.  If it happens, immediately dilute with 120 to 240 mL of water or milk (not to exceed 120 mL in a child). Alternatively, administer anti-acids. Dilution may only be helpful if performed in the first seconds to minutes after ingestion  
  • For significant vomiting and/or diarrhea, treat dehydration with IV fluids as necessary  
  • Mild to moderate allergic reactions may be treated with   antihistamines with or without inhaled beta-adrenergic agonists, corticosteroids or epinephrine.  
  • Treatment of severe anaphylaxis also includes oxygen supplementation, aggressive airway management, epinephrine, ECG monitoring, and IV fluids.  

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