Demeclocycline

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Demeclocycline
Demeclocycline.png
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 names Declomycin
AHFS/Drugs.com monograph
MedlinePlus a682103
Pregnancy cat.
Legal status
  • Prescription only
Routes Oral
Pharmacokinetic data
Bioavailability 60–80%
Protein binding 41–50%
Metabolism Hepatic
Half-life 10–17 hours
Excretion Renal
Identifiers
CAS number 127-33-3 YesY
64-73-3 (HCl)
ATC code D06AA01 J01AA01
PubChem CID 5311063
DrugBank DB00618
ChemSpider 10482117 YesY
UNII 5R5W9ICI6O YesY
KEGG D03680 YesY
ChEBI CHEBI:4392 YesY
ChEMBL CHEMBL1591 YesY
Chemical data
Formula C21H21ClN2O8 
Mol. mass 464.853 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]

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treatment at the time.[5] Demeclocycline has since been the drug of choice for treating SIADH, although it may be superseded as vasopressin receptor antagonists, such as tolvaptan, become available.[5]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]

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]

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]

As with related tetracycline antibiotics, demeclocycline acts by binding to the 30S ribosomal subunit to inhibit binding of aminoacyl tRNA 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]

  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. doi:10.7326/0003-4819-83-5-654. 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.