Demeclocycline

Template:Short description Template:Cs1 configTemplate:Main other {{#invoke:Infobox|infobox}}Template:Template other{{#invoke:TemplatePar |check |template=Template:Infobox_drug |all= |opt= pronounce= pronounce_ref= pronounce_comment= ATC_prefix= ATC_suffix= ATC_supplemental= ATCvet= biosimilars= CAS_number_Ref= CAS_number= CAS_supplemental= ChEBI= ChEBI_Ref= ChEMBL_Ref= ChEMBL= ChemSpiderID= ChemSpiderID_Ref= chirality= class= container_only= DailyMedID= data_page= DrugBank_Ref= DrugBank= Drugs.com= duration_of_action= INN= INN_EMA= IUPAC_name= IUPHAR_ligand= KEGG_Ref= KEGG= MedlinePlus= NIAID_ChemDB= PDB_ligand= PubChemSubstance= PubChem= StdInChIKey_Ref= StdInChIKey= StdInChI_Ref= StdInChI_comment= StdInChI= UNII_Ref= UNII= DTXSID= Verifiedfields= Watchedfields= addiction_liability= alt2= altL= altR= alt= bioavailability= boiling_high= boiling_notes= boiling_point= captionLR= caption= caption2= charge= chemical_formula= chemical_formula_ref= chemical_formula_comment= class1= class2= class3= class4= class5= class6= component1= component2= component3= component4= component5= component6= density= density_notes= dependency_liability= drug_name= elimination_half-life= engvar= excretion= image2= imageL= imageR= image= image_class= image_class2= image_classL= image_classR= Jmol= legal_AU= legal_BR= legal_CA= legal_DE= legal_EU= legal_NZ= legal_UK= legal_UN= legal_US= legal_AU_comment= legal_BR_comment= legal_CA_comment= legal_DE_comment= legal_UK_comment= legal_NZ_comment= legal_US_comment= legal_UN_comment= legal_EU_comment= legal_status= licence_CA= licence_EU= licence_US= license_CA= license_EU= license_US= mab_type= melting_high= melting_notes= melting_point= metabolism= metabolites= molecular_weight= molecular_weight_round= molecular_weight_unit= molecular_weight_ref= molecular_weight_comment= onset= pregnancy_AU= pregnancy_AU_comment= pregnancy_category= protein_bound= routes_of_administration= SMILES= smiles= solubility= sol_units= source= specific_rotation= synonyms= target= tradename= type= vaccine_type= verifiedrevid= width2= widthL= widthR= width= AAN= BAN= JAN= USAN= source_tissues= target_tissues= receptors= agonists= antagonists= precursor= biosynthesis= gt_target_gene= gt_vector= gt_nucleic_acid_type= gt_editing_method= gt_delivery_method= sec_combustion= Ac=Ag=Al=Am=Ar=As=At=Au=B=Ba=Be=Bh=Bi=Bk=Br=C=Ca=Cd=Ce=Cf=Cl=Cm=Cn=Co=Cr=Cs=Cu= D=Db=Ds=Dy=Er=Es=Eu=F=Fe=Fl=Fm=Fr=Ga=Gd=Ge=H=He=Hf=Hg=Ho=Hs=I=In=Ir=K=Kr=La=Li=Lr=Lu=Lv= Mc=Md=Mg=Mn=Mo=Mt=N=Na=Nb=Nd=Ne=Nh=Ni=No=Np=O=Og=Os=P=Pa=Pb=Pd=Pm=Po=Pr=Pt=Pu=Ra=Rb=Re=Rf=Rg=Rh=Rn=Ru=S=Sb=Sc=Se=Sg=Si=Sm=Sn=Sr=Ta=Tb=Tc=Te=Th=Ti=Tl=Tm=Ts=U=V=W=Xe=Y=Yb=Zn=Zr= index_label= index2_label= index_comment= index2_comment= CAS_number2= CAS_supplemental2= ATC_prefix2= ATC_suffix2= ATC_supplemental2= PubChem2= PubChemSubstance2= IUPHAR_ligand2= DrugBank2= ChemSpiderID2= UNII2= KEGG2= ChEBI2= ChEMBL2= PDB_ligand2= NIAID_ChemDB2= SMILES2= smiles2= StdInChI2= StdInChIKey2= CAS_number2_Ref= ChEBI2_Ref= ChEMBL2_Ref= ChemSpiderID2_Ref= DrugBank2_Ref= KEGG2_Ref= StdInChI2_Ref= StdInChIKey2_Ref= UNII2_Ref= DTXSID2= QID= QID2=PLLR= pregnancy_US= pregnancy_US_comment= |cat=Pages using infobox drug with unknown parameters |format=0|errNS=0

|preview=

}}{{Infobox drug/maintenance categoriesTemplate:Yesno | drug_name = | INN = | _drugtype =

| _has_physiological_data= | _has_gene_therapy=

| vaccine_type= | mab_type= | _number_of_combo_chemicals={{#invoke:ParameterCount |main |component1 |component2 |component3 |component4|component5|component6 }} | _vaccine_data= | _mab_data= | _mab_vaccine_data= | _mab_other_data=212128NC(=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)C1S/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/s1FMTDIUIBLCQGJB-SEYHBJAFSA-NTemplate:StdinchiciteTemplate:Stdinchicite | _combo_data= | _physiological_data= | _clinical_data=Template:Drugs.coma682103 OralDeclomycinD06Template:ATC | _legal_data=Rx-only

| _other_data=(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

| _image_0_or_2 = demeclocycline 2D skeletaldemeclocycline 3D BS | _image_LR =

| _datapage = Demeclocycline (data page) | _vaccine_target={{#ifeq: | vaccine | | _type_not_vaccine }} | _legal_all=Rx-only | _ATC_prefix_supplemental=D06Template:ATC | _has_EMA_link = | CAS_number=127-33-3 | PubChem=54680690 | ChemSpiderID=10482117 | ChEBI=4392 | ChEMBL=1591 | DrugBank=DB00618 | KEGG=D03680 | _hasInChI_or_Key={{#if: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/s1FMTDIUIBLCQGJB-SEYHBJAFSA-N |yes}} | UNII=5R5W9ICI6O | _hasJmol02 = |_hasMultipleCASnumbers = |_hasMultiplePubChemCIDs = |_hasMultipleChEBIs =

| _countSecondIDs={{#invoke:ParameterCount |main |CAS_number2 |ATC_prefix2 |PubChem2 |PubChemStructure2 |IUPHAR_ligand2 |DrugBank2 |ChemSpiderID2 |UNII2 |KEGG2 |ChEBI2 |ChEMBL2 |PDB_ligand2 |NIAID_ChemDB2 |SMILES2 |smiles2 |StdInChI2 |StdInChIKey2 |DTXCID2}} | _countIndexlabels={{#invoke:ParameterCount |main |index_label |index2_label}} | _trackListSortletter= |QID = |QID2 = |Verifiedfields= |Watchedfields= |verifiedrevid=460775334}}

Demeclocycline (INN, BAN, USAN, brand name Declomycin) is a tetracycline antibiotic which was derived from a mutant strain of Streptomyces aureofaciens.<ref name="Chopra">Template:Cite journal</ref><ref name="Elks2014">Template:Cite book</ref>

Uses

Demeclocycline is officially indicated for the treatment of various types of bacterial infections.<ref name="DailyMed">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> It is used as an antibiotic in the treatment of Lyme disease,<ref>Template:Cite book</ref> acne,<ref>Template:Cite journal</ref> and bronchitis.<ref>Template:Cite journal</ref> Resistance, though, is gradually becoming more common,<ref name="Schnappinger">Template:Cite journal</ref> and demeclocycline is now rarely used for treatment of infections.<ref name="Klein">Template:Cite journal</ref><ref name="Lexi-Comp">{{#invoke:citation/CS1|citation |CitationClass=web }} Retrieved on October 27, 2008.</ref>

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.<ref name="Goh">Template:Cite journal</ref> Physiologically, this works by reducing the responsiveness of the collecting tubule cells to ADH.<ref>Template:Cite journal</ref>

The use in SIADH actually relies on a side effect; demeclocycline induces nephrogenic diabetes insipidus (dehydration due to the inability to concentrate urine).<ref name=Goh/><ref>Template:Cite journal</ref><ref name="Miell">Template:Cite journal</ref>

The use of demeclocycline in SIADH was first reported in 1975,<ref name="Cherrill">Template:Cite journal</ref> 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.<ref name="Tolstoi">Template:Cite journal</ref> Demeclocycline used to be the drug of choice for treating SIADH.<ref name=Miell/> Meanwhile, it might be superseded, now that vasopressin receptor antagonists, such as tolvaptan, became available.<ref name=Tolstoi/>

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.<ref name="Lexi-Comp" />

Side effects and interactions

The side effects are similar to those of other tetracyclines. Skin reactions with sunlight have been reported.<ref name=Tolstoi/> Like only few other known tetracycline derivatives, demeclocycline causes nephrogenic diabetes insipidus.<ref name="Cox">Template:Cite book</ref> Furthermore, demeclocycline might have psychotropic side effects similar to lithium.<ref>Template:Cite journal</ref>

Tetracyclines bind to cations, such as calcium, iron (when given orally), and magnesium, rendering them insoluble and nonadsorbable for the gastrointestinal tract. Demeclocycline should not be taken with food (particularly milk and other dairy products) or antacids.<ref name=Lexi-Comp/>

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).<ref name="Chopra" /><ref name="Schnappinger" />

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.<ref name="FliersKorbonits2014">Template:Cite book</ref><ref name="KovácsLichardus2012">Template:Cite book</ref><ref name="SinghWilliams2009">Template:Cite book</ref> Exactly how demeclocycline does this has yet to be elucidated, however.<ref name="SinghWilliams2009" />

Brand names

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