| Indication |
Used primarily to treat Lyme disease, acne, and bronchitis. Also
indicated (but rarely used) to treat urinary tract infections, gum
disease, malaria, and other bacterial infections such as gonorrhea and
chlamydia. One of its other registered uses is the treatment of
hyponatremia (low blood sodium concentration) due to the syndrome of
inappropriate antidiuretic hormone (SIADH) where fluid restriction alone
has been ineffective. |
| Pharmacodynamics |
Demeclocycline is a tetracycline antibiotic active against the following microorganisms: Rickettsiae (Rocky Mountain spotted fever, typhus fever and the typhus group, Q fever, rickettsial pox, tick fevers), Mycoplasma pneumoniae
(PPLO, Eaton agent), agents of psittacosis and ornithosis, agents of
lymphogranulomavenereum and granuloma inguinale, the spirochetal agent
of relapsing fever (Borrelia recurrentis), Haemophilus ducreyi (chancroid), Yersinia pestis, Pasteurella pestis and Pasteurella tularensis, Bartonella bacilliformis, Bacteroides species, Vibrio comma and Vibrio fetus, and Brucella species
(in conjunction with streptomycin). Demeclocycline inhibits cell growth
by inhibiting translation. Demeclocycline is lipophilic and can easily
pass through the cell membrane or passively diffuses through porin
channels in the bacterial membrane. Demeclocycline is bacteriostatic (it
impairs bacterial growth but does not kill bacteria directly). Because
it is excreted more slowly than tetracycline, it maintains effective
blood levels for longer periods of time. |
| Mechanism of action |
Demeclocycline inhibits cell growth by inhibiting translation. It
binds (reversibly) to the 30S and 50S ribosomal subunit and prevents the
amino-acyl tRNA from binding to the A site of the ribosome, which
impairs protein synthesis by bacteria. The binding is reversible in
nature. The use in SIADH actually relies on a side-effect of
tetracycline antibiotics; many may cause diabetes insipidus (dehydration
due to the inability to concentrate urine). It is not completely
understood why demeclocycline impairs the action of antidiuretic
hormone, but it is thought that it blocks the binding of the hormone to
its receptor. |
| Absorption |
Tetracyclines are readily absorbed. |
| Volume of distribution |
Not Available |
| Protein binding |
41-50% |
| Metabolism |
Hepatic |
| Route of elimination |
Demeclocycline hydrochloride, like other tetracyclines, is
concentrated in the liver and excreted into the bile where it is found
in much higher concentrations than in the blood. Following a single 150
mg dose of demeclocycline hydrochloride in normal volunteers, 44% (n =
8) was excreted in urine and 13% and 46%, respectively, were excreted in
feces in two patients within 96 hours as active drug. |
| Half life |
10-17 hours |
| Clearance |
- Renal cl=35 mL/min/1.73 m2
|
| Toxicity |
Oral, rat: LD50 = 2372 mg/kg |
