Details of Drug Interaction

Details of Drug-Drug Interaction

 Drug General Information (ID: DDI0CD1SHY)
  Drug Name Bendroflumethiazide Drug Info Nabumetone Drug Info
  Drug Type Small molecule Small molecule
  Therapeutic Class Antihypertensive Agents Nsaids/Analgesics
  Structure

 Mechanism of Bendroflumethiazide-Nabumetone Interaction (Severity Level: Moderate)
     Antagonize the effect of antihypertensive agents Click to Show/Hide Mechanism Graph
Could Not Find 2D Structure
      Drug Name Bendroflumethiazide Nabumetone
      Mechanism Antihypertensive agent Hypertensive effects
Prostaglandin G/H synthase  Inhibitor
      Key Mechanism Factor 1
Factor Name Prostaglandin G/H synthase 2
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Structure Sequence
MLARALLLCAVLALSHTANPCCSHPCQNRGVCMSVGFDQYKCDCTRTGFYGENCSTPEFLTRIKLFLKPTPNTVHYILTHFKGFWNVVNNIPFLRNAIMSYVLTSRSHLIDSPPTYNADYGYKSWEAFSNLSYYTRALPPVPDDCPTPLGVKGKKQLPDSNEIVEKLLLRRKFIPDPQGSNMMFAFFAQHFTHQFFKTDHKRGPAFTNGLGHGVDLNHIYGETLARQRKLRLFKDGKMKYQIIDGEMYPPTVKDTQAEMIYPPQVPEHLRFAVGQEVFGLVPGLMMYATIWLREHNRVCDVLKQEHPEWGDEQLFQTSRLILIGETIKIVIEDYVQHLSGYHFKLKFDPELLFNKQFQYQNRIAAEFNTLYHWHPLLPDTFQIHDQKYNYQQFIYNNSILLEHGITQFVESFTRQIAGRVAGGRNVPPAVQKVSQASIDQSRQMKYQSFNEYRKRFMLKPYESFEELTGEKEMSAELEALYGDIDAVELYPALLVEKPRPDAIFGETMVEVGAPFSLKGLMGNVICSPAYWKPSTFGGEVGFQIINTASIQSLICNNVKGCPFTSFSVPDPELIKTVTINASSSRSGLDDINPTVLLKERSTEL
Gene Name PTGS2
Uniprot ID PGH2_HUMAN
KEGG Pathway hsa:5743
Protein Family Prostaglandin G/H synthase family
Protein Function
Dual cyclooxygenase and peroxidase in the biosynthesis pathway of prostanoids, a class of C20 oxylipins mainly derived from arachidonate, with a particular role in the inflammatory response (PubMed:7947975, PubMed:7592599, PubMed:9261177, PubMed:16373578, PubMed:22942274, PubMed:26859324, PubMed:27226593, PubMed:11939906, PubMed:19540099). The cyclooxygenase activity oxygenates arachidonate (AA, C20:4(n-6)) to the hydroperoxy endoperoxide prostaglandin G2 (PGG2), and the peroxidase activity reduces PGG2 to the hydroxy endoperoxide PGH2, the precursor of all 2-series prostaglandins and thromboxanes (PubMed:7947975, PubMed:7592599, PubMed:9261177, PubMed:16373578, PubMed:22942274, PubMed:26859324, PubMed:27226593). This complex transformation is initiated by abstraction of hydrogen at carbon 13 (with S-stereochemistry), followed by insertion of molecular O2 to form the endoperoxide bridge between carbon 9 and 11 that defines prostaglandins. The insertion of a second molecule of O2 (bis-oxygenase activity) yields a hydroperoxy group in PGG2 that is then reduced to PGH2 by two electrons (PubMed:7947975, PubMed:7592599, PubMed:9261177, PubMed:16373578, PubMed:22942274, PubMed:26859324, PubMed:27226593). Similarly catalyzes successive cyclooxygenation and peroxidation of dihomo-gamma-linoleate (DGLA, C20:3(n-6)) and eicosapentaenoate (EPA, C20:5(n-3)) to corresponding PGH1 and PGH3, the precursors of 1- and 3-series prostaglandins (PubMed:11939906, PubMed:19540099). In an alternative pathway of prostanoid biosynthesis, converts 2-arachidonoyl lysophopholipids to prostanoid lysophopholipids, which are then hydrolyzed by intracellular phospholipases to release free prostanoids (PubMed:27642067). Metabolizes 2-arachidonoyl glycerol yielding the glyceryl ester of PGH2, a process that can contribute to pain response (PubMed:22942274). Generates lipid mediators from n-3 and n-6 polyunsaturated fatty acids (PUFAs) via a lipoxygenase-type mechanism. Oxygenates PUFAs to hydroperoxy compounds and then reduces them to corresponding alcohols (PubMed:11034610, PubMed:11192938, PubMed:9048568, PubMed:9261177). Plays a role in the generation of resolution phase interaction products (resolvins) during both sterile and infectious inflammation (PubMed:12391014). Metabolizes docosahexaenoate (DHA, C22:6(n-3)) to 17R-HDHA, a precursor of the D-series resolvins (RvDs) (PubMed:12391014). As a component of the biosynthetic pathway of E-series resolvins (RvEs), converts eicosapentaenoate (EPA, C20:5(n-3)) primarily to 18S-HEPE that is further metabolized by ALOX5 and LTA4H to generate 18S-RvE1 and 18S-RvE2 (PubMed:21206090). In vascular endothelial cells, converts docosapentaenoate (DPA, C22:5(n-3)) to 13R-HDPA, a precursor for 13-series resolvins (RvTs) shown to activate macrophage phagocytosis during bacterial infection (PubMed:26236990). In activated leukocytes, contributes to oxygenation of hydroxyeicosatetraenoates (HETE) to diHETES (5,15-diHETE and 5,11-diHETE) (PubMed:22068350, PubMed:26282205). During neuroinflammation, plays a role in neuronal secretion of specialized preresolving mediators (SPMs) 15R-lipoxin A4 that regulates phagocytic microglia (By similarity).
    Click to Show/Hide
      Mechanism Description
  • Antagonize the effect of Bendroflumethiazide when combined with Nabumetone 

Recommended Action
      Management In patients receiving both diuretic and NSAID therapy, management consists of avoiding dehydration and carefully monitoring the patient's renal function and blood pressure. If renal insufficiency or hyperkalemia develops, both drugs should be discontinued until the condition is corrected.

References
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21 Product Information. HydroDIURIL (hydrochlorothiazide). Merck & Co, Inc, West Point, PA.
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