Introduction

Let’s take a quick glance at the pharmacology of tetracyclines – drugs which interfere with bacterial protein synthesis. In this way, they share a common mechanism of action with macrolides – such as azithromycin, clarithromycin, and erythromycin – and with aminoglycosides – such as gentamicin, netilmicin, and tobramycin. Other drugs – such as lincosamides and streptogramins – also interfere with protein synthesis. Tetracyclines are bacteriostatic in effect and have a broad spectrum of activity. They are incompletely absorbed from the gut, particularly when taken with food. Common side effects include nausea, tooth discolouration, and headache.

Examples of Tetracyclines
Minocycline Oxytetracycline Doxycycline Tetracycline

Pharmacology of Tetracyclines

Tetracyclines are antibacterial drugs used in the treatment of a wide variety of infections. They are broad spectrum in effect – being active against many Gram positive and Gram negative infections. For example, they are effective against infections caused by Chlamydia trachomatis, Chlamydia psittaci, Mycoplasma, rickettsiae, Brucella, Vibrio cholera, and Coxiella burnetii.

Tetracyclines are commonly used in the treatment of acne. Doxycycline is also used in the treatment of anthrax infections, bubonic plague, malaria treatment and prophylaxis, and elephantiasis. Unlike other tetracyclines, minocycline is effective against Neisseria meningitides. However, resistance still remains a problem. Tetracyclines carry resistance through plasmids – resulting in bacterial cells shuttling (efflux) more and more of the drug out of the cell.

Tetracyclines

Bacterial resistance of tetracyclines can also occur through decreased binding of tetracyclines to the bacterial ribosome. As a result of mechanisms such as this, bacterial resistance to tetracyclines is growing. It’s no accident that resistance can occur through tetracycline binding at the bacterial ribosome, as it’s from this site that tetracyclines exert their mechanism of action.

It’s a fundamental fact of the pharmacology of tetracyclines that they act by interfering with bacterial protein synthesis. More specifically, tetracyclines inhibit the binding of aminoacyl-tRNA to the mRNA-ribosome complex – something which is achieved by the tetracycline drug binding to the 30S ribosomal subunit.

Pharmacokinetics

Tetracyclines are incompletely absorbed from the gut, an effect enhanced if the drug is taken with food. The absorption of tetracycline antibiotics is also impaired if taken with:

  • Calcium
  • Aluminium salts
  • Magnesium salts
  • Iron

When tetracyclines bind to these salts, they form di- and trivalent cations – which are inactive chelates. As a result, patients are advised to avoid foods such as milk, and supplements (such as antacids). Absorption is further impaired if the intestinal pH is elevated.

Tetracylines can also cross the placenta, and they are poorly absorbed into the CSF. Their half-lives vary somewhat, mostly oscillating around the 9-20 hour mark. Tetracyclines are mostly concentrated in the liver, with part of the drug being eliminated in the bile (though some of this eliminated drug is reabsorbed thereafter).

Unwanted effects

Before concluding our understanding of the pharmacology of tetracyclines, we quickly turn to their unwanted effects. Tetracyclines may cause:

  • Nausea, vomiting, epigastric pain
  • Anti-anabolic effects
  • Headache, visual disturbances (benign intracranial hypertension)
  • Phototoxicity

Tetracyclines cause tooth discolouration, which also occurs in the developing fetus if taken during pregnancy. Tooth discolouration is also a risk in the developing child, or in children whose teeth are still developing. Tetracyclines are also known to cause steatosis and fatty liver, meaning they are used with caution in patients with liver dysfunction.

Test your knowledge of the pharmacology of tetracyclines here– ten questions covering just about everything in this article.

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