Demeclocycline

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Demeclocycline
Systematic (IUPAC) name
(2E,4S,4aS,5aS,6S,12aS)-2-[amino(hydroxy)methylidene]-7-chloro-4-(dimethylamino)-6,10,11,12a-tetrahydroxy-1,2,3,4,4a,5,5a,6,12,12a-decahydrotetracene-1,3,12-trione
Clinical data
Trade namesDeclomycin
AHFS/Drugs.commonograph
MedlinePlusa682103
Pregnancy cat.D (US)
Legal status Prescription only
RoutesOral
Pharmacokinetic data
Bioavailability60–80%
Protein binding41–50%
MetabolismHepatic
Half-life10–17 hours
ExcretionRenal
Identifiers
CAS number127-33-3 YesY
64-73-3 (HCl)
ATC codeD06AA01 J01AA01
PubChemCID 5311063
DrugBankDB00618
ChemSpider10482117 YesY
UNII5R5W9ICI6O YesY
KEGGD03680 YesY
ChEBICHEBI:4392 YesY
ChEMBLCHEMBL1591 YesY
Chemical data
FormulaC21H21ClN2O8 
Mol. mass464.853 g/mol
 YesY (what is this?)  (verify)
 
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Demeclocycline
Systematic (IUPAC) name
(2E,4S,4aS,5aS,6S,12aS)-2-[amino(hydroxy)methylidene]-7-chloro-4-(dimethylamino)-6,10,11,12a-tetrahydroxy-1,2,3,4,4a,5,5a,6,12,12a-decahydrotetracene-1,3,12-trione
Clinical data
Trade namesDeclomycin
AHFS/Drugs.commonograph
MedlinePlusa682103
Pregnancy cat.D (US)
Legal status Prescription only
RoutesOral
Pharmacokinetic data
Bioavailability60–80%
Protein binding41–50%
MetabolismHepatic
Half-life10–17 hours
ExcretionRenal
Identifiers
CAS number127-33-3 YesY
64-73-3 (HCl)
ATC codeD06AA01 J01AA01
PubChemCID 5311063
DrugBankDB00618
ChemSpider10482117 YesY
UNII5R5W9ICI6O YesY
KEGGD03680 YesY
ChEBICHEBI:4392 YesY
ChEMBLCHEMBL1591 YesY
Chemical data
FormulaC21H21ClN2O8 
Mol. mass464.853 g/mol
 YesY (what is this?)  (verify)

Demeclocycline (marketed as Declomycin, Declostatin, and Ledermycin) is a tetracycline antibiotic derived from a strain of Streptomyces aureofaciens.[1]

Uses[edit source | edit]

It is officially indicated for the treatment of various types of bacterial infections.[2] It is used as an antibiotic in the treatment of Lyme disease, acne, and bronchitis.[citation needed] Resistance, though, is gradually becoming more common, and demeclocycline is now rarely used for infections.

It is widely used (though off-label in many countries) in the treatment of hyponatremia (low blood sodium concentration) due to the syndrome of inappropriate antidiuretic hormone (SIADH) when fluid restriction alone has been ineffective.[3] Physiologically, this works by reducing the responsiveness of the collecting tubule cells to ADH.

The use in SIADH actually relies on a side effect; demeclocycline induces nephrogenic diabetes insipidus (dehydration due to the inability to concentrate urine).[3] The use of demeclocycline in SIADH was first reported in 1975,[4] and, in 1978, a larger study found it to be more effective and better tolerated than lithium carbonate, the only available treatment at the time.[5] Demeclocycline has since been the drug of choice for treating SIADH, although it may be superseded as vasopressin receptor antagonists, such as tolvaptan, become available.[5]

Contraindications[edit source | edit]

Like other tetracyclines, demeclocycline is contraindicated in children and pregnant or nursing women. All members of this class interfere with bone development and may discolour teeth.[6]

Side effects and interactions[edit source | edit]

These are similar to those of other tetracyclines. Skin reactions with sunlight have been reported.[5] Demeclocycline is unique in that it is the only tetracycline known to cause nephrogenic diabetes insipidus.

Tetracyclines bind to cations, such as calcium, iron (when given orally), and magnesium, rendering them insoluble and inabsorbable for the gastrointestinal tract. Demeclocycline should not be taken with food (particularly milk and other dairy products) or antacids.[6]

Mechanism of action[edit source | edit]

As with related tetracycline antibiotics, demeclocycline acts by binding to the 30S and 50S ribosomal subunits, which impairs protein synthesis by bacteria. It is bacteriostatic (it impairs bacterial growth, but does not kill bacteria directly).

It is not completely understood why demeclocycline impairs the action of antidiuretic hormone, but is thought to block the binding of the hormone from its receptor.[7]

References[edit source | edit]

  1. ^ "demeclocycline" at Dorland's Medical Dictionary
  2. ^ "DailyMed: About DailyMed". Retrieved 2008-12-20. 
  3. ^ a b Goh KP (May 2004). "Management of hyponatremia". American Family Physician 69 (10): 2387–94. PMID 15168958. 
  4. ^ Cherrill DA, Stote RM, Birge JR, Singer I (November 1975). "Demeclocycline treatment in the syndrome of inappropriate antidiuretic hormone secretion". Annals of Internal Medicine 83 (5): 654–6. PMID 173218. 
  5. ^ a b c Tolstoi LG (2002). "A brief review of drug-induced syndrome of inappropriate secretion of antidiuretic hormone". Medscape Pharmacotherapy 4 (1).  Retrieved on October 27, 2008.
  6. ^ a b Lexi-Comp (August 2008). "Demeclocycline". The Merck Manual Professional.  Retrieved on October 27, 2008.
  7. ^ De Troyer A, Demanet JC (1975). "Correction of antidiuresis by demeclocycline". N Engl J Med 293 (18): 915–8. doi:10.1056/NEJM197510302931809. PMID 170519.