DT-Web

DB00687 - Fludrocortisone


Identification
Name Fludrocortisone
Accession Number DB00687 (APRD00756, DB02478)
Type small molecule
Description A synthetic mineralocorticoid with anti-inflammatory activity. [PubChem]
Structure
MOL SDF PDB SMILES InChI
Categories (*)
Molecular Weight 380.4504
Groups approved
Monoisotopic Weight 380.199902243
Pharmacology
Indication For partial replacement therapy for primary and secondary adrenocortical insufficiency in Addison's disease and for the treatment of salt-losing adrenogenital syndrome.
Mechanism of action Fludrocortisone binds the mineralocorticoid receptor (aldosterone receptor). This binding (or activation of the mineralocorticoid receptor by fludrocortisone) in turn causes an increase in ion and water transport and thus raises extracellular fluid volume and blood pressure and lowers potassium levels.
Absorption Not Available
Protein binding High
Biotransformation Hepatic, some renal.
Route of elimination Not Available
Toxicity Effects of overexposure include irritation, cardiac edema, increased blood volume, hypertension, cardiac arrhythmias, enlargement of the heart, headaches, and weakness of the extremities.
Affected organisms
  • Humans and other mammals
Interactions
Drug Interactions
Drug Mechanism of interaction
Acenocoumarol The corticosteroid, fludrocortisone, alters the anticoagulant effect, acenocoumarol.
Acetylsalicylic acid The corticosteroid, fludrocortisone, may decrease the effect of the salicylate, acetylsalicylic acid.
Ambenonium The corticosteroid, fludrocortisone, may decrease the effect of the anticholinesterase, ambenonium.
Amobarbital The barbiturate, amobarbital, may decrease the effect of the corticosteroid, fludrocortisone.
Anisindione The corticosteroid, fludrocortisone, alters the anticoagulant effect of anisindione.
Aprobarbital The barbiturate, aprobarbital, may decrease the effect of the corticosteroid, fludrocortisone.
Bismuth Subsalicylate The corticosteroid, fludrocortisone, may decrease the effect of the salicylate, bismuth subsalicylate.
Butabarbital The barbiturate, butabarbital, may decrease the effect of the corticosteroid, fludrocortisone.
Butalbital The barbiturate, butalbital, may decrease the effect of the corticosteroid, fludrocortisone.
Butethal The barbiturate, butethal, may decrease the effect of the corticosteroid, fludrocortisone.
Dicumarol The corticosteroid, fludrocortisone, alters the anticoagulant effect of dicumarol.
Dihydroquinidine barbiturate The barbiturate, dihydroquinidine barbiturate, may decrease the effect of the corticosteroid, fludrocortisone.
Edrophonium The corticosteroid, fludrocortisone, may decrease the effect of the anticholinesterase, edrophonium.
Ethotoin The enzyme inducer, ethotoin, may decrease the effect of the corticosteroid, fludrocortisone.
Fosphenytoin The enzyme inducer, fosphenytoin, may decrease the effect of the corticosteroid, fludrocortisone.
Heptabarbital The barbiturate, heptabarbital, may decrease the effect of the corticosteroid, fludrocortisone.
Hexobarbital The barbiturate, hexobarbital, may decrease the effect of the corticosteroid, fludrocortisone.
Magnesium salicylate The corticosteroid, fludrocortisone, may decrease the effect of magnesium salicylate.
Mephenytoin The enzyme inducer, mephenytoin, may decrease the effect of the corticosteroid, fludrocortisone.
Methohexital The barbiturate, methohexital, may decrease the effect of the corticosteroid, fludrocortisone.
Methylphenobarbital The barbiturate, methylphenobarbital, may decrease the effect of the corticosteroid, fludrocortisone.
Midodrine Increased arterial pressure
Neostigmine The corticosteroid, fludrocortisone, may decrease the effect of the anticholinesterase, neostigmine.
Pentobarbital The barbiturate, pentobarbital, may decrease the effect of the corticosteroid, fludrocortisone.
Phenobarbital The barbiturate, phenobarbital, may decrease the effect of the corticosteroid, fludrocortisone.
Phenytoin The enzyme inducer, phenytoin, may decrease the effect of the corticosteroid, fludrocortisone.
Primidone The barbiturate, primidone, may decrease the effect of the corticosteroid, fludrocortisone.
Pyridostigmine The corticosteroid, fludrocortisone, may decrease the effect of the anticholinesterase, pyridostigmine.
Quinidine barbiturate The barbiturate, quinidine barbiturate, may decrease the effect of the corticosteroid, fludrocortisone.
Rifampin The enzyme inducer, rifampin, may decrease the effect of the corticosteroid, fludrocortisone.
Salicylate-sodium The corticosteroid, fludrocortisone, may decrease the effect of the salicylate, salicylate-sodium.
Salsalate The corticosteroid, fludrocortisone, may decrease the effect of the salicylate, salsalate.
Secobarbital The barbiturate, secobarbital, may decrease the effect of the corticosteroid, fludrocortisone.
Tacrine Tacrine and Fludrocortisone may independently exacerbate muscle weakness in myasthenia gravis patients. Monitor for additive muscle weakness effects.
Talbutal The barbiturate, talbutal, may decrease the effect of the corticosteroid, fludrocortisone.
Trastuzumab Trastuzumab may increase the risk of neutropenia and anemia. Monitor closely for signs and symptoms of adverse events.
Trisalicylate-choline The corticosteroid, fludrocortisone, may decrease the effect of the salicylate, trisalicylate-choline.
Vecuronium Vecuronium may increase the adverse neuromuscular effects of systemic corticosteroids, such as Fludrocortisone. Monitor for increased muscle weakness and signs of polyneuropathies and myopathy.
Warfarin The corticosteroid, fludrocortisone, alters the anticoagulant effect of warfarin.
Food Interactions
  • Take with food to reduce irritation.
  • Avoid excess salt/sodium unless otherwise instructed by your physician.

Targets


Mineralocorticoid receptor
Name Mineralocorticoid receptor
Gene Name NR3C2
Pharmacological action yes
Actions agonist
References
  • Otte C, Jahn H, Yassouridis A, Arlt J, Stober N, Maass P, Wiedemann K, Kellner M: The mineralocorticoid receptor agonist, fludrocortisone, inhibits pituitary-adrenal activity in humans after pre-treatment with metyrapone. Life Sci. 2003 Aug 22;73(14):1835-45. - Pubmed
  • Oelkers W, Buchen S, Diederich S, Krain J, Muhme S, Schoneshofer M: Impaired renal 11 beta-oxidation of 9 alpha-fluorocortisol: an explanation for its mineralocorticoid potency. J Clin Endocrinol Metab. 1994 Apr;78(4):928-32. - Pubmed
  • Young MJ, Funder JW: Mineralocorticoids, salt, hypertension: effects on the heart. Steroids. 1996 Apr;61(4):233-5. - Pubmed
  • Kingsley-Kallesen M, Mukhopadhyay SS, Wyszomierski SL, Schanler S, Schutz G, Rosen JM: The mineralocorticoid receptor may compensate for the loss of the glucocorticoid receptor at specific stages of mammary gland development. Mol Endocrinol. 2002 Sep;16(9):2008-18. - Pubmed
  • Buckley TM, Mullen BC, Schatzberg AF: The acute effects of a mineralocorticoid receptor (MR) agonist on nocturnal hypothalamic-adrenal-pituitary (HPA) axis activity in healthy controls. Psychoneuroendocrinology. 2007 Jul 29;. - Pubmed
  • Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. - Pubmed
DTHybrid score 0.4371
Glucocorticoid receptor
Name Glucocorticoid receptor
Gene Name NR3C1
Pharmacological action unknown
Actions agonist
References
  • Trune DR, Kempton JB: Low dose combination steroids control autoimmune mouse hearing loss. J Neuroimmunol. 2010 Aug 26. - Pubmed
DTHybrid score 0.8368
Androgen receptor
Name Androgen receptor
Gene Name AR
Pharmacological action unknown
Actions agonist
References
  • Krishnan AV, Zhao XY, Swami S, Brive L, Peehl DM, Ely KR, Feldman D: A glucocorticoid-responsive mutant androgen receptor exhibits unique ligand specificity: therapeutic implications for androgen-independent prostate cancer. Endocrinology. 2002 May;143(5):1889-900. - Pubmed
  • Matias PM, Carrondo MA, Coelho R, Thomaz M, Zhao XY, Wegg A, Crusius K, Egner U, Donner P: Structural basis for the glucocorticoid response in a mutant human androgen receptor (AR(ccr)) derived from an androgen-independent prostate cancer. J Med Chem. 2002 Mar 28;45(7):1439-46. - Pubmed
DTHybrid score 1.1063

Predictions


Id Partner name Gene Name Score
232 Corticosteroid-binding globulin SERPINA6 0.2544
4512 Cytochrome P450 3A4 CYP3A4 0.115
614 Progesterone receptor PGR 0.0914
3811 Cytochrome P450 19A1 CYP19A1 0.071
1588 Multidrug resistance protein 1 ABCB1 0.0603
756 Sex hormone-binding globulin SHBG 0.0508
4118 Cytochrome P450 3A5 CYP3A5 0.0488
6023 Cytochrome P450 11B2, mitochondrial CYP11B2 0.044
6139 Solute carrier organic anion transporter family member 1A2 SLCO1A2 0.0402
469 Annexin A1 ANXA1 0.0385
364 Corticosteroid 11-beta-dehydrogenase isozyme 1 HSD11B1 0.0375
4924 Cytochrome P450 2C8 CYP2C8 0.0353
805 Cytochrome P450 11B1, mitochondrial CYP11B1 0.0351
6107 Cytochrome P450 3A7 CYP3A7 0.0346
723 Cytosolic phospholipase A2 PLA2G4A 0.0316
6228 Nuclear receptor coactivator 1 NCOA1 0.0313
380 Cytochrome P450 17A1 CYP17A1 0.0302
290 Prostaglandin G/H synthase 2 PTGS2 0.0276
381 Prolactin receptor PRLR 0.0272
3923 Cholinesterase BCHE 0.0242
136 Estrogen receptor ESR1 0.0232
6016 Cytochrome P450 2C19 CYP2C19 0.0188
4119 Cytochrome P450 2D6 CYP2D6 0.0166
4757 Cytochrome P450 2C9 CYP2C9 0.0156
6220 Aryl hydrocarbon receptor AHR 0.0152
6024 Cytochrome P450 1A1 CYP1A1 0.0151
1735 Canalicular multispecific organic anion transporter 1 ABCC2 0.0139
6241 Nuclear receptor coactivator 2 NCOA2 0.013
4110 Voltage-dependent L-type calcium channel subunit beta-2 CACNB2 0.0129
4115 Voltage-dependent L-type calcium channel subunit alpha-1D CACNA1D 0.0129
4111 Voltage-dependent L-type calcium channel subunit alpha-1S CACNA1S 0.0128
478 Voltage-dependent L-type calcium channel subunit alpha-1C CACNA1C 0.0125
3810 Catechol O-methyltransferase COMT 0.0119
4200 Cytochrome P450 1A2 CYP1A2 0.0109
2751 Holliday junction ATP-dependent DNA helicase ruvB ruvB 0.0105
4755 Holliday junction ATP-dependent DNA helicase ruvB ruvB 0.0105
4114 Voltage-dependent L-type calcium channel subunit beta-3 CACNB3 0.0101
4112 Voltage-dependent L-type calcium channel subunit beta-4 CACNB4 0.0101
118 Organic cation/carnitine transporter 2 SLC22A5 0.01
6022 UDP-glucuronosyltransferase 1-1 UGT1A1 0.0096
4113 Voltage-dependent L-type calcium channel subunit alpha-1F CACNA1F 0.0094
1898 Cytochrome P450 1B1 CYP1B1 0.0094
4615 Chain A, Red Copper Protein Nitrosocyanin NE0143 0.0093
333 Voltage-dependent L-type calcium channel subunit beta-1 CACNB1 0.0091
587 Serum albumin ALB 0.0089
3941 Amine oxidase [flavin-containing] A MAOA 0.0084
596 3-oxo-5-alpha-steroid 4-dehydrogenase 1 SRD5A1 0.0082
5718 Cytochrome P450 2A6 CYP2A6 0.0079
6048 Troponin C, skeletal muscle TNNC2 0.0078
3939 Amine oxidase [flavin-containing] B MAOB 0.0078
4120 NADPH--cytochrome P450 reductase POR 0.0074
6017 Cholesterol side-chain cleavage enzyme, mitochondrial CYP11A1 0.0074
650 Aldo-keto reductase family 1 member C3 AKR1C3 0.0071
1758 GTPase HRas HRAS 0.0068
6030 Cytochrome P450 2B6 CYP2B6 0.0067
217 Estradiol 17-beta-dehydrogenase 1 HSD17B1 0.0066
6047 Calcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1A PDE1A 0.0064
862 Multidrug resistance-associated protein 1 ABCC1 0.0064
1649 Small inducible cytokine A2 CCL2 0.0063
4604 Liver carboxylesterase 1 CES1 0.0061
5692 Calcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1B PDE1B 0.0061
6500 Phospholipase A2 PLA2G1B 0.006
6141 Sodium/bile acid cotransporter SLC10A1 0.0059
1561 Troponin C, slow skeletal and cardiac muscles TNNC1 0.0056
4160 Voltage-dependent calcium channel subunit alpha-2/delta-2 CACNA2D2 0.0056
226 Gonadotropin-releasing hormone receptor GNRHR 0.0054
373 Transthyretin TTR 0.0054
964 Voltage-dependent T-type calcium channel subunit alpha-1H CACNA1H 0.005
762 Voltage-dependent calcium channel subunit alpha-2/delta-1 CACNA2D1 0.005
6147 Solute carrier family 22 member 3 SLC22A3 0.0048
776 Bile salt export pump ABCB11 0.0047
2300 Lysozyme E 0.0047
3633 Lysozyme R 0.0047
5597 Lysozyme 17 0.0047
465 Calmodulin CALM1 0.0043
6145 Solute carrier family 22 member 1 SLC22A1 0.004
6142 Solute carrier family 22 member 8 SLC22A8 0.004
20 Prostaglandin G/H synthase 1 PTGS1 0.0039
1732 ATP-binding cassette sub-family G member 2 ABCG2 0.0037
1729 Solute carrier family 22 member 6 SLC22A6 0.0037
6144 Solute carrier family 22 member 2 SLC22A2 0.0032
6031 Cytochrome P450 3A43 CYP3A43 0.0028
84 Nuclear receptor 0B1 NR0B1 0.0023
6014 Cytochrome P450 2A13 CYP2A13 0.0018
468 Cytochrome P450 4A11 CYP4A11 0.0014
833 Organic cation/carnitine transporter 1 SLC22A4 0.0011
7 Nitric oxide synthase, inducible NOS2 0.0011
6143 Solute carrier family 22 member 7 SLC22A7 0.001
6013 Cytochrome P450 2E1 CYP2E1 0.0008
↑