Tetracyclines

The Basic Structure of Tetracyclines

Introduction

This group of antibiotics is named after the four hydrocarbon rings that make up the core of each of the drugs. Water soluble drugs are: Tetracycline, Oxytetracycline and Chlorotetracycline. Lipid soluble drugs are; Minocycline and Doxycycline.

Mechanism of Action

Tetracyclines work by inhibiting cell growth and so are bacteriostatic. They are brought into susceptible organisms by active uptake and then they inhibit translation. It binds to part of the ribosomal subunit and prevents tRNA from binding to the A site of the ribosome. This results in the inhibition of protein synthesis.

Spectrum of Activity

They are very broad antimicrobial agents.

• They are active against gram-positive bacteria, except enterococci and group D Streptococci.
• They are active against non-enteric gram-negative bactaeria. Pseudomonas and enterbacteriaceae are often resistant.
• They are active against Chlamydophila, Rickettsia, Mycoplasma and a range of protozoa.
• Resistance has now become widespread.

Pharmacokinetic Considerations

The water soluble tetracyclines are moderately lipophilic and the lipid soluble ones are very lipophilic. They are orally active, though presence of food decreases the absorption of the drug. This is especially the case when Ca²⁺ is present as it will chelate the drug. They have a wide volume of distribution but are unable to penetrate the CSF.

Water soluble forms are excreted in the bile and urine unchanged. Of the lipid soluble drugs doxcycline is excreted in the faeces by a combination of the drug in bile and through diffusion of the intestinal wall. Minocycline undergoes some metabolism in the liver before it is excreted in the bile.

Side Effects and Contraindications

• Due to their nature to be chelated by Ca²⁺ they tend to deposit in developing bones and teeth, resulting in staining and sometimes dental hypoplasia and bone deformaties. In man it is suggested not to give it to the young or pregnant animals.
• Gastrointestinal upsets are known to occur following oral administration, especially in horses and should be avoided in this species as much as possible.
• Collapse has been reported on intravenous administration of the drug.
• Nephrotoxicity has been reported because of high dose related changes in the renal tubule.
• In cattle it has been known that high doses result in fatty infiltration of the liver. This hepatotoxic nature of the drug means that they shouldn't be used if hepatic impairment is suspected.
• Oxytetracycline is irritant to tissues, especially in long-acting forms and shouldn't be used in small animals and horses.
• Doxycycline can cause oesophagitis and should be avoided if an animal is dysphagic or is vomiting.
• In man phototoxicity is a reported side-effect.