Tetracyclines

The tetracyclines are a large group of drugs with a common basic structure and activity. Tetracyclines are classified as short acting (chlortetracycline, tetracycline, oxytetracycline), intermediate acting (demeclocycline and methacycline), or long-acting (doxycycline and minocycline) based on serum half-lives.

Antimicrobial activity: Tetracyclines are broad-spectrum antibiotics. They are active against for many gram-positive and gram-negative bacteria, including anaerobes, rickettsiae, chlamydiae, mycoplasmas, and are active against some protozoa. The main mechanisms of resistance to tetracycline is decreased intracellular accumulation due to either impaired influx or increased efflux by an active transport protein pump.

Pharmacokinetics: Tetracyclines mainly differ in their absorption after oral administration and their elimination. Doxycycline better absorbed after oral administration than tetracycline. A portion of an orally administered dose of tetracycline remains in the gut lumen, modifies intestinal flora, and is excreted in the feces. Absorption occurs mainly in the upper small intestine and is impaired by food (except doxycycline and minocycline); by divalent cations (Ca2+< , Mg2< +, Fe2+< ) or Al3+< ; by dairy products and antacids, which contain multivalent cations; and by alkaline pH. They are distributed widely to tissues and body fluids except for cerebrospinal fluid. Minocycline reaches very high concentrations in tears and saliva, which makes it useful for eradication of the meningococcal carrier state. Tetracyclines cross the placenta to reach the fetus and are also excreted in milk. Doxycycline, in contrast to other tetracyclines, is eliminated by nonrenal mechanisms.

Clinical uses: A tetracycline is the drug of choice in infections with Mycoplasma pneumoniae, chlamydiae, rickettsiae, and some spirochetes. They are used in combination regimens to treat gastric and duodenal ulcer disease caused by Helicobacter pylori. They may be employed in various gram-positive and gram-negative bacterial infections, including Vibrio infections. A tetracycline in combination with an aminoglycoside is indicated for plague, tularemia, and brucellosis. Tetracyclines are sometimes employed in the treatment of E. histolytica or P. falciparum.

Adverse reactions

Gastrointestinal adverse effects: Nausea, vomiting, and diarrhea are the most common and these effects are attributable to direct local irritation of the intestinal tract. Tetracyclines suppress susceptible coliform organisms and causes overgrowth of Pseudomonas, Proteus, staphylococci, resistant coliforms, clostridia, and Candida. This can result in intestinal functional disturbances, anal pruritus, vaginal or oral candidiasis, or enterocolitis (associated with Clostridium difficile) with shock and death. Pseudomembranous enterocolitis should be treated with metronidazole.

Bony structures and teeth:   Tetracyclines are readily bound to calcium deposited in newly formed bone or teeth in young children. It causes discoloration, and enamel dysplasia; they can also be deposited in bone, where it may cause deformity or growth inhibition. If the drug is given to children under 8 years of age for long periods, similar changes can result.

They are hepato and nephrotoxic drug, the also induce sensitivity to sunlight (demeclocycine) and vestibular reactions (doxycycline, and minocycline).

Macrolides: include erythromycin, clarithromycin and azithromycin.