[Clinical use of tetracyclines in the treatment of periodontal diseases].

INTRODUCTION

There are a number of chemically different tetracycline homologues. The older group of tetracyclines, which was introduced in the 1950-60s, includes tetracycline, oxytetracycline, chlortetracycline and demeclocycline. The newer group of tetracyclines includes doxycycline, methacycline and minocycline.

PHARMACOKINETICS

Elevated concentration of tetracycline in gingival fluid with respect to blood levels was an unexpected phenomenon. Patients given 250 mg every 6 hours had average crevicular fluid concentrations between 4 to 8 g/ml and blood concentrations between 2 to 2.5 g/ml after 48 hours. The levels in crevicular fluid and blood of volunteers who received 250 mg every 12 hours were 2 to 4 g/ml and 0.3 to 1.4 g/ml respectively after 48 hours. The concentration of doxycycline in gingival fluid after administration of 200 mg/1st day and then 100 mg/day achieved average level of 6 g/ml. Minocycline, a semisynthetic derivate of tetracycline, has shown to yield gingival fluid levels 5 times as high as serum levels after administration of 100 mg every 12 hours.

MECHANISMS OF ACTION

Tetracycline and its derivates demonstrate high in vitro activity against most periodontal bacteria, including Actinobacillus actinomycetemcomitans, Porphyromonas gingivalis, Prevotella intermedia, Eikenella corrodens, Wolinella recta and Fusobacterium nucleatum. The study of in vitro susceptibility of these 6 bacterial strains showed that, in regard to blood level, minimal inhibitory concentration is higher and it is the concentration of the drug that can be expected in gingival fluid following oral administration of 100 mg per day (doxycycline) (Table 1). The anti-inflammatory effect of tetracyclines was demonstrated histologically not only by reducing the size of the infiltrated connective tissue, but qualitative changes were also observed. Golub and associates have presented evidence that tetracyclines inhibit collagenase activity in gingival fluid and in tissue cultures. Therapeutic concentrations of tetracycline inhibit chemotaxis, phagocytosis and random migration of neutrophils in vitro.

ADVERSE EFFECTS

Great amounts of tetracyclines cause gastrointestinal disorders, nausea, vomiting and diarrhea. Tetracyclines suppress activity of the enzymes in the bowel and pancreas. During longlasting administration they can damage the liver and kidneys. Tetracyclines can cause photo-sensibilization. They make deposits with calcium in bones, specially during prenatal period and during growth, so they can cause permanent teeth discoloration and hypoplasia.

INTERACTIONS

The most important interaction is with penicillin. These two kinds of antibiotics antagonize and decrease the therapeutic effect of each other, so their administration at the same time should be avoided. A significant interaction occurs between tetracyclines and metal ions. This interaction often has been observed in conjunction with use of various antacids. Tetracyclines can also influence the production and absorption of vitamin K. Nephrotoxicity has been reported when tetracyclines have been administrated in conjunction with methoxyflurane.

INDICATIONS

Doxycycline, due to its advantages over tetracycline (Table 2), is indicated in treating destructive periodontal diseases including: juvenile periodontitis and refractory marginal periodontitis. Doxycycline therapy may be used for acute periodontal abscess and if the conditions are accompanied by general symptoms. Prophylactic application is recommended for implant placement procedures including membranes in guided tissue regeneration.

RESULTS OF CLINICAL STUDY

ORAL APPLICATION: In spite of great number of published investigations this paper presents only the results of placebo-controlled, double-blind studies. There is evidence that therapy in localized juvenile periodontitis should eliminate Actinobacillus actinomycetemcomitans, since 95% of patients harbored this bacteria. (ABSTRACT TRUNCATED)