Demeclocycline Explained

Verifiedrevid:460775334
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
Tradename:Declomycin
Pregnancy Us:D
Legal Status:Rx-only
Routes Of Administration:Oral
Bioavailability:60–80%
Protein Bound:41–50%
Metabolism:Hepatic
Elimination Half-Life:10–17 hours
Excretion:Renal
Cas Number:127-33-3
Cas Supplemental:
(HCl)
Atc Prefix:D06
Atc Suffix:AA01
Pubchem:54680690
Drugbank:DB00618
Chemspiderid:10482117
Unii:5R5W9ICI6O
Kegg:D03680
Chebi:4392
Chembl:1591
Synonyms:RP-10192, demethylchlortetracycline
C:21
H:21
Cl:1
N:2
O:8
Smiles:NC(=O)C1C(=O)[C@@]2(O)C(O)=C3C(=O)c4c(O)ccc(Cl)c4[C@@H](O)[C@H]3C[C@H]2C(C=1O)N(C)C
Stdinchi:1S/C21H21ClN2O8/c1-24(2)14-7-5-6-10(16(27)12-9(25)4-3-8(22)11(12)15(6)26)18(29)21(7,32)19(30)13(17(14)28)20(23)31/h3-4,6-7,14-15,25-26,28-29,32H,5H2,1-2H3,(H2,23,31)/t6-,7-,14-,15-,21-/m0/s1
Stdinchikey:FMTDIUIBLCQGJB-SEYHBJAFSA-N

Demeclocycline (INN, BAN, USAN, brand name Declomycin) is a tetracycline antibiotic which was derived from a mutant strain of Streptomyces aureofaciens.[1] [2]

Uses

Demeclocycline is officially indicated for the treatment of various types of bacterial infections.[3] It is used as an antibiotic in the treatment of Lyme disease,[4] acne,[5] and bronchitis.[6] Resistance, though, is gradually becoming more common,[7] and demeclocycline is now rarely used for treatment of infections.[8] [9]

It is widely used (though off-label in many countries including the United States) 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.[10] Physiologically, this works by reducing the responsiveness of the collecting tubule cells to ADH.[11]

The use in SIADH actually relies on a side effect; demeclocycline induces nephrogenic diabetes insipidus (dehydration due to the inability to concentrate urine).[10] [12] [13]

The use of demeclocycline in SIADH was first reported in 1975,[14] 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treatment at the time.[15] Demeclocycline used to be the drug of choice for treating SIADH.[13] Meanwhile, it might be superseded, now that vasopressin receptor antagonists, such as tolvaptan, became available.[15]

Contraindications

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.

Side effects and interactions

The side effects are similar to those of other tetracyclines. Skin reactions with sunlight have been reported.[15] Like only few other known tetracycline derivatives, demeclocycline causes nephrogenic diabetes insipidus.[16] Furthermore, demeclocycline might have psychotropic side effects similar to lithium.[17]

Tetracyclines bind to cations, such as calcium, iron (when given orally), and magnesium, rendering them insoluble and inadsorbable for the gastrointestinal tract. Demeclocycline should not be taken with food (particularly milk and other dairy products) or antacids.[9]

Mechanism of action

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).

Demeclocycline inhibits the renal action of antidiuretic hormone by interfering with the intracellular second messenger cascade (specifically, inhibiting adenylyl cyclase activation) after the hormone binds to vasopressin V2 receptors in the kidney.[18] [19] [20] Exactly how demeclocycline does this has yet to be elucidated, however.

Brand names

Brand names include Declomycin, Declostatin, Ledermycin, Bioterciclin, Deganol, Deteclo, Detravis, Meciclin, Mexocine, and Clortetrin.

Notes and References

  1. Chopra I, Hawkey PM, Hinton M . Tetracyclines, molecular and clinical aspects . The Journal of Antimicrobial Chemotherapy . 29 . 3 . 245–277 . March 1992 . 1592696 . 10.1093/jac/29.3.245 .
  2. Book: Elks J . The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies. 14 November 2014. Springer. 978-1-4757-2085-3. 356–.
  3. Web site: Demeclocycline Hydrochloride - demeclocycline tablet . DailyMed . U.S. National Library of Medicine . 2008-12-20.
  4. Book: Rosner B . 2007 . The Antibiotic Rotational Protocol . The Top 10 Lyme Disease Treatments: Defeat Lyme Disease with the Best of Conventional and Alternative Medicine. 84, 86. BioMed Publishing . 9780976379713. https://books.google.com/books?id=J4TFtQeHkQAC&pg=PA84.
  5. Ad Hoc Committee report: systemic antibiotics for treatment of acne vulgaris: efficacy and safety . Archives of Dermatology . 111 . 12 . 1630–1636 . December 1975 . 128326 . 10.1001/archderm.1975.01630240086015 .
  6. Beatson JM, Marsh BT, Talbot DJ . A clinical comparison of pivmecillinam plus pivampicillin (Miraxid) and a triple tetracycline combination (Deteclo) in respiratory infections treated in general practice . The Journal of International Medical Research . 13 . 4 . 197–202 . 1985 . 3930309 . 10.1177/030006058501300401 . 23485353 .
  7. Schnappinger D, Hillen W . Tetracyclines: antibiotic action, uptake, and resistance mechanisms . Archives of Microbiology . 165 . 6 . 359–369 . June 1996 . 8661929 . 10.1007/s002030050339 . 1996ArMic.165..359S . 6199423 .
  8. Klein NC, Cunha BA . Tetracyclines . The Medical Clinics of North America . 79 . 4 . 789–801 . July 1995 . 7791423 . 10.1016/S0025-7125(16)30039-6 . free .
  9. Web site: Demeclocycline . August 2008 . Lexi-Comp . The Merck Manual Professional. Retrieved on October 27, 2008.
  10. Goh KP . Management of hyponatremia . American Family Physician . 69 . 10 . 2387–2394 . May 2004 . 15168958 . 2008-10-28 . dead . https://web.archive.org/web/20081016200608/http://www.aafp.org/afp/20040515/2387.html . 2008-10-16 .
  11. Kortenoeven ML, Sinke AP, Hadrup N, Trimpert C, Wetzels JF, Fenton RA, Deen PM . Demeclocycline attenuates hyponatremia by reducing aquaporin-2 expression in the renal inner medulla . American Journal of Physiology. Renal Physiology . 305 . 12 . F1705–F1718 . December 2013 . 24154696 . 10.1152/ajprenal.00723.2012 . 17815411 .
  12. Hayek A, Ramirez J . Demeclocycline-induced diabetes insipidus . JAMA . 229 . 6 . 676–677 . August 1974 . 4277429 . 10.1001/jama.1974.03230440034026 .
  13. Miell J, Dhanjal P, Jamookeeah C . Evidence for the use of demeclocycline in the treatment of hyponatraemia secondary to SIADH: a systematic review . International Journal of Clinical Practice . 69 . 12 . 1396–1417 . December 2015 . 26289137 . 5042094 . 10.1111/ijcp.12713 .
  14. Cherrill DA, Stote RM, Birge JR, Singer I . Demeclocycline treatment in the syndrome of inappropriate antidiuretic hormone secretion . Annals of Internal Medicine . 83 . 5 . 654–656 . November 1975 . 173218 . 10.7326/0003-4819-83-5-654 .
  15. Tolstoi LG . A brief review of drug-induced syndrome of inappropriate secretion of antidiuretic hormone . . 4 . 1 . 2002 . https://web.archive.org/web/20130606112813/https://www.medscape.com/viewarticle/420687_print . June 6, 2013.
  16. Book: Cox M . 1982 . Porter GA . Nephrotoxic Mechanisms of Drugs and Environmental Toxins . Springer . Boston, MA . 165–177 . Tetracycline Nephrotoxicity . 978-1-4684-4216-8 . 10.1007/978-1-4684-4214-4_15 . https://books.google.com/books?id=EKPqBwAAQBAJ&pg=PA165.
  17. Mørk A, Geisler A . A comparative study on the effects of tetracyclines and lithium on the cyclic AMP second messenger system in rat brain . Progress in Neuro-Psychopharmacology & Biological Psychiatry . 19 . 1 . 157–169 . January 1995 . 7708928 . 10.1016/0278-5846(94)00112-U . 36219362 .
  18. Book: Verbalis JG . Disorders of water metabolism . Clinical Neuroendocrinology . Fliers E, Korbonits M, Romijn JA . Handbook of Clinical Neurology . 124 . 37–52 (43) . 2014 . 25248578 . 10.1016/B978-0-444-59602-4.00003-4 . https://books.google.com/books?id=qH9zAwAAQBAJ&pg=PA43 . Elsevier Science . 978-0-444-62612-7 .
  19. Book: Kovács L, Lichardus B . Vasopressin: Disturbed Secretion and Its Effects. 6 December 2012. Springer Science & Business Media. 978-94-009-0449-1. 180–.
  20. Book: Singh AK, Williams GH . Textbook of Nephro-Endocrinology. 12 January 2009. Academic Press. 978-0-08-092046-7. 251–.

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