Pharmacology of Tetracyclines

Tetracyclines are a class of broad-spectrum antibiotics that are effective against a wide variety of bacteria. They are commonly used to treat infections of the respiratory tract, skin, and urinary system, as well as certain sexually transmitted infections and acne. Below is a comprehensive overview of the pharmacology of tetracyclines:

Classification

Tetracyclines include several drugs within this class:

• Tetracycline
• Doxycycline
• Minocycline
• Tigecycline​¹​.

Mechanism of Action

Tetracyclines primarily exert their antimicrobial effects by inhibiting bacterial protein synthesis. They achieve this by binding to the 30S ribosomal subunit, which prevents the aminoacyl-tRNA from binding to the A site of the ribosome, thereby halting the translation process. They also have some binding affinity to the 50S ribosomal subunit but to a lesser extent. Besides, tetracyclines may alter the cytoplasmic membrane of bacteria, leading to leakage of intracellular contents such as nucleotides​^{2, 3}​.

They act by penetrating the bacterial cell wall and binding to the 30S ribosome, inhibiting the protein synthesis required to make the cellular wall​⁴​.

Pharmacokinetics

1. Absorption:
   • The bioavailability is less than 40% when administered via intramuscular injection, 100% intravenously, and 60-80% orally (in fasting adults). Food and/or milk can reduce gastrointestinal absorption of oral preparations of tetracycline by 50% or more.
2. Protein Binding:
   • They are 20 – 67% protein-bound.
3. Metabolism:
   • Tetracyclines are not metabolized.
4. Route of Elimination:
   • They are concentrated by the liver in the bile and excreted in the urine and feces at high concentrations in a biologically active form.
5. Half-life:
   • The half-life of tetracyclines is between 6-12 hours​³​.

Adverse Effects

1. Gastrointestinal Disturbances:
   • Common gastrointestinal side effects include nausea, vomiting, and diarrhea. Tetracyclines can cause Clostridium difficile-induced diarrhea (pseudomembranous colitis) and candidal superinfections​^5, ​​⁶​.
2. Esophageal Erosions:
   • If not taken with sufficient water, tetracyclines can cause esophageal erosions​⁵​.
3. Hepatic Effects:
   • There can be fatty liver occurrences associated with tetracycline use​⁵​.
4. Cardiac Effects:
   • Chest pain has been noted among the adverse effects of tetracyclines​⁷​.
5. Bone and Dental Effects:
   • In children and fetuses, tetracyclines can cause staining of teeth, hypoplasia of dental enamel, and abnormal bone growth. Additionally, in infants, they may cause idiopathic intracranial hypertension and bulging fontanelles​⁸​.

Clinical Uses

• Respiratory Tract Infections: Such as pneumonia and bronchitis.
• Skin and Soft Tissue Infections: Including acne and rosacea.
• Urinary Tract Infections
• Sexually Transmitted Infections: Such as chlamydia and gonorrhea.
• Lyme Disease: Doxycycline is the drug of choice.
• Malaria Prophylaxis: Doxycycline can be used for prevention in travelers.

Resistance

Bacterial resistance to tetracyclines can occur due to efflux pumps (which pump the drug out of the bacterial cell), ribosomal protection proteins (which protect the ribosome from the drug), or enzymatic inactivation.

Drug Interactions

• Calcium, Iron, Magnesium, and Aluminum: Can reduce the absorption of tetracyclines.
• Oral Contraceptives: Tetracyclines may reduce the efficacy of oral contraceptives.
• Warfarin: Tetracyclines may increase the anticoagulant effects of warfarin.

Contraindications

• Pregnancy and Breastfeeding: Tetracyclines can affect bone and tooth development in the fetus and newborn⁹​​.
• Children Under 8 Years: Due to the risk of tooth discoloration and inhibition of bone growth​⁸​.

Current Status

Tetracyclines have endured as essential antibiotics over the years owing to their broad-spectrum antimicrobial activity. However, the emergence of bacterial resistance and the advent of other antibiotic classes with fewer adverse effects have somewhat overshadowed their usage. Nevertheless, they continue to be crucial, especially in settings where other antibiotics might not be as effective or accessible. The range of conditions they are employed against, from acne and rosacea to more severe infections caused by susceptible gram-positive and gram-negative bacteria, underscores their enduring relevance in contemporary medical practice.

Conclusion

Tetracyclines are versatile antibiotics with a broad spectrum of activity. However, their use must be carefully considered due to the potential for adverse effects and the increasing prevalence of bacterial resistance. Appropriate dosing, awareness of drug interactions, and monitoring for side effects are crucial for safe and effective use.