Tetracyclines

crop_square Key points

  • check_circle Bacteriostatic antibiotics with a core structure of four hydrocarbon rings
  • check_circle Inhibit bacterial protein synthesis by binding to the 30S subunit of the bacterial ribosome
  • check_circle Very broad spectrum of activity including atypical bacteria and some protozoa
  • check_circle Adverse effects include increased photosensitivity and tooth discolouration

crop_square Background and biochemistry

Tetracyclines were isolated from Streptomyces fungi. The term 'tetracycline' (singular) is the name of one specific drug, which was the first synthetically modified natural antibiotic on the market. 'Tetracyclines' (plural) refers to a class of antibiotics, even though some members of this class were discovered prior to the eponymous tetracycline. All tetracyclines share a core structure consisting of four ('tetra') hydrocarbon rings ('cycles'). Tetracycline antibiotics have distinct side groups, which determine some pharmacokinetic properties (e.g., half-life). Tigecycline is a recently developed antibiotic of the glycylcycline subgroup, a derivate of tetracycline.

crop_square Mechanism of action

Tetracyclines interfere with bacterial protein biosynthesis. They enter cells through porin channels and bind to the 30S subunit of the bacterial ribosome. This inhibits the binding of aminoacyl tRNA, effectively blocking the production of bacterial proteins. Tetracyclines are primarily bacteriostatic but may be bactericidal at higher concentrations. Bacterial resistance to tetracyclines occurs due to efflux pumps reducing intracellular drug concentration, modifications to the ribosomal binding site and alterations of cell membrane proteins. Tigecycline was developed to overcome common bacterial resistance mechanisms.

crop_square Drugs and spectrum of activity

  • Tetra­cycline
  • Demeclo­cycline
  • Doxy­cycline
  • Mino­cycline
  • Tige­cycline

Tetracyclines are active against a broad range of organisms. They are the drugs of choice against intracellular bacteria like Chlamydia spp and Rickettsia spp. Tetracyclines may be used to treat spirochaetal infections. Tigecycline shows improved activity against gram-positive bacteria and covers many bacterial strains resistant to other tetracyclines.

crop_square Pharmacokinetics

Tetracyclines are well absorbed after oral administration and show good tissue penetration. Tigecycline can only be given intravenously. Half-lives vary from as little as 6h for tetracycline to more than 24h for tigecycline. They cross the blood-brain barrier insufficiently except for doxycycline. Most tetracyclines are eliminated both via the urine and the faeces with varying proportions.

crop_square Adverse drug effects

Adverse effects include increased photosensitivity, gastrointestinal upset, and skin rashes. Changes to patients' microbiota due to tetracycline therapy may lead to enterocolitis. Depositions of tetracyclines in bony structures may cause discolouration of teeth.