The tetracyclines are a group of drugs with common basic chemical structures, antimicrobial activity, and pharmacologic properties. Antimicrobial Activity
Tetracyclines are inhibitors of protein synthesis and are bacteriostatic
for many gram-positive and gram-negative bacteria. They are strongly
inhibitory for the growth of mycoplasmas, rickettsiae, chlamydiae,
spirochetes, and some protozoa (eg, amebas). Their antipneumococcal activity
approaches that of the macrolides; almost all H influenzae are
inhibited. Tetracyclines also have some activity against some vancomycin-resistant
enterococci. Doxycycline and minocycline are potential options for therapy
of staphylococcal infections, including infections with many methicillin-resistant
strains. There are marked in vitro differences between tetracyclines
with respect to staphylococci. Tetracycline-resistant staphylococci
often retain susceptibility to doxycycline and minocycline and doxycycline-resistant S aureus can still be susceptible to minocycline. Tetracyclines
have little utility in the treatment of gram-negative aerobic infection.
However, minocycline is reliable in its activity against S
maltophilia. Pharmacokinetics & Administration Oral bioavailability varies depending on the drug. Absorption is impaired by dairy products, aluminum hydroxide gels (antacids), and chelation with divalent cations, eg, Ca2+ or Fe2+. Chelation is less problematic with doxycycline and minocycline when compared with tetracycline. Consequently, doses of tetracyclines should be staggered at least 2 hours before or after receipt of multivalent cations. Oral bioavailability is moderate with tetracycline and highest with doxycycline and minocycline (95% or more). Lipid solubility of minocycline and doxycycline accounts for their penetration into the cerebrospinal fluid, prostate, tears, and saliva.
Tetracyclines are primarily metabolized in the liver and excreted
in bile. Doxycycline requires no dosage adjustment in kidney disease;
in contrast, other tetracyclines should be avoided or given in reduced
dosage. For patients unable to take oral medication, some tetracyclines (doxycycline, minocycline) are formulated for parenteral administration in doses similar to the oral ones. Clinical Uses
Tetracyclines are drugs of choice for infections with Chlamydia,
Mycoplasma, Rickettsia, Ehrlichia, and Vibrio organisms
and for some spirochetal infections. Sexually transmitted diseases
in which chlamydiae often play a role—endocervicitis, urethritis,
proctitis, and epididymitis—should be treated with doxycycline
for 7–14 days. Pelvic inflammatory disease is often treated
with doxycycline plus cefoxitin or cefotetan. Other chlamydial infections
(psittacosis, lymphogranuloma venereum, trachoma) and sexually transmitted
diseases (granuloma inguinale) also respond to doxycycline. Other
uses include treatment of acne, respiratory infections, Lyme disease
and relapsing fever, brucellosis, glanders, tularemia (often in combination
with streptomycin), cholera, mycoplasmal pneumonia, actinomycosis, nocardiosis,
malaria, infections caused by M marinum and Pasteurella species
(typically after an animal bite), and as malaria prophylaxis (including
multidrug-resistant P falciparum). They also have
been used in combination with other drugs for amebiasis, falciparum malaria,
and recurrent ulcers due to H pylori. Because of
generally good activity against pneumococci; H influenzae; and Chlamydia,
Legionella, and Mycoplasma organisms, doxycycline
should be considered as a potential empiric therapy for mild to
moderate outpatient pneumonia. Doxycycline and minocycline are increasingly considered
as options in the treatment of community-onset skin and soft tissue
infection due to methicillin-resistant S aureus. As discussed previously, minocycline and doxycycline are superior to tetracycline in the
treatment of methicillin-resistant S aureus; doxycycline-resistant isolates are often still inhibited by minocycline. Minocycline is equally as efficacious as doxycycline for the therapy of nongonococcal urethritis and cervicitis. Adverse Effects Allergy Hypersensitivity reactions with fever or skin rashes are uncommon. Gastrointestinal Side Effects Diarrhea, nausea, and anorexia are common. Tetracycline administration,
particularly doxycycline and minocycline, should be avoided at bedtime
due to the risk of esophageal erosion. Bones and Teeth
Tetracyclines are bound to calcium deposited in growing bones
and teeth, causing fluorescence, discoloration, enamel dysplasia,
deformity, or growth inhibition. Therefore, tetracyclines should
not be given to pregnant women, nursing women, or children under
8 years of age. Liver Damage
Tetracyclines can impair hepatic function or even cause liver
necrosis, particularly in the presence of preexisting liver disease. Kidney Effects Demeclocycline can cause nephrogenic diabetes insipidus and has been used therapeutically to treat inappropriate antidiuretic hormone secretion. Tetracyclines, particularly tetracycline, may increase blood urea nitrogen (BUN) due to their antianabolic activity. Other Tetracyclines—principally demeclocycline—may induce photosensitization, especially in fair-skinned individuals. Minocycline induces vestibular reactions (dizziness, vertigo, nausea, vomiting), with a frequency of 35–70% after doses of 200 mg daily and has also been implicated as a cause of hypersensitivity pneumonitis. |