Tetracyclines Pharmacology!

Tetracyclines Pharmacology

Tetracyclines are among the most widely prescribed antibacterial agents. Here, in this brief study of tetracyclines pharmacology, we review the must-know facts about this important antibacterial drug class.

Tetracyclines have been around since the 1940s.

However, their efficacy has gone into decline, not least due to the development of bacterial resistance. Despite these rising levels of resistance, tetracyclines remain an important antibacterial drug class in the treatment of a wide range of bacterial infections.

Tetracyclines have a broad-spectrum of activity, being active against a number of Gram-positive and Gram-negative infections.

Indications of tetracyclines therefore include:

• Moderate-to-severe acne and rosacea
• Lower respiratory tract infections – COPD exacerbations, pneumonia (both typical and atypical pneumonia)
• Chlamydial infection – including pelvic inflammatory disease
• Typhoid
• Anthrax
• Lyme disease
• Syphilis
• Brucellosis
• Malaria prophylaxis

Prominent examples of the tetracycline antibacterials include:

• Tetracycline
• Doxycycline
• Minocycline
• Tigecycline
• Demeclocycline
• Oxytetracycline

Before we review the therapeutic considerations of tetracyclines, let’s take a few minutes to review their pharmacology – the means through which tetracyclines work to achieve their therapeutic effects.

Mechanism of Action

Tetracyclines are protein synthesis inhibitors.

More specifically, tetracyclines prevent the binding of aminoacyl-tRNA to the mRNA-ribosome complex. This prevents both the formation and elongation of the polypeptide chain – a process they inhibit at the 30S ribosomal subunit.

This process is bacteriostatic – meaning that tetracyclines prevent further bacterial growth rather than actively kill bacterial cells. This assists the body’s natural defenses to overcome the infection over time.

As we have learned, resistance is common and continues to develop.

Resistance occurs through three main means. First, the formation of the efflux pump. With the efflux pump, bacteria can “pump” out tetracyclines from the cell. Second, enzymatic inactivation also occurs, though this is a much rarer cause of resistance. A third method, namely ribosomal protection, can also take place – where bacteria prevent tetracyclines from binding to the bacterial ribosomal subunit.

Side Effects

Common side effects with tetracyclines include:

• Phototoxicity – increasing the risk of sunburn
• Gastrointestinal effects – nausea, bowel upset, diarrhea
• Tooth discoloration – hence contraindicated in pregnancy
• Enamel hypoplasia
• Esophageal irritation
• Intracranial hypertension (rarely!)

Taking expired tetracyclines can cause Fanconi syndrome – a syndrome characterized by impaired absorption of electrolytes and substances from the proximal tubules of the kidney.

Hypersensitivity reactions are rare (both immediate and delayed), occurring in approximately 1 percent of patients.

Clinical Pharmacology

When we discuss the clinical pharmacology of tetracyclines, we must consider the following factors.

• Tetracyclines are avoided in pregnancy because they bind to teeth and bones during fetal development, infancy, and early childhood. Tetracyclines should be avoided in children under 12 years.
• Taking tetracyclines with multivalent ions – such as zinc, calcium, aluminum, or magnesium – can chelate and render useless the therapeutic function of these medicines. Tetracyclines should not be administered with dietary supplements or antacids that contain these ions. At least 2-hours should elapse, both before and after tetracycline administration, before these ions/supplements are taken. However, taking tetracyclines with food is often recommended to avoid nausea and vomiting when taken on an empty stomach.
• Tetracyclines may worsen symptoms in patients with myasthenia gravis.
• That by killing colonic gut flora which otherwise produces vitamin K, tetracyclines enhance the anticoagulant effect of warfarin.
• That tetracyclines, in some patients, can cause steatosis and liver toxicity. Monitoring may be required with long-term use – for example, in patients on high-dose tetracycline treatment for severe acne.
• Demeclocycline is used off-label in the treatment of hyponatremia due to SIADH (syndrome of inappropriate anti-diuretic hormone) because of its inhibition of antidiuretic hormone after it binds to vasopressin V2 receptors in the kidney.
• In September 2010, a black-box warning was issued for tigecycline. Tigecycline increases the risk of death in patients with certain severe infections, such as ventilator-associated pneumonia.
• Doxycycline is used as prophylaxis against anthrax infection, which is caused by the organism, Bacillus anthracis.
• Tetracyclines should be avoided in patients with renal impairment because decreased drug clearance can lead to effects such as hepatic toxicity, increased BUN and consequent azotemia, and hyperphosphatemia.
• Tetracyclines are administered orally, typically in tablet or capsule form. Patients are counseled to take tetracyclines with a full glass of water to prevent esophageal irritation and/or discomfort.

That completes our rapid revision review of tetracyclines pharmacology! Check back to our pharmacy blog soon for more exclusive content to help you master the science of drugs and medicines.