Drug General Information (ID: DDI8QJK1RX)
  Drug Name Indapamide Drug Info Nitrous acid Drug Info
  Drug Type Small molecule Small molecule
  Therapeutic Class Antihypertensive Agents Antidotes
  Structure

 Mechanism of Indapamide-Nitrous acid Interaction (Severity Level: Moderate)
     Additive hypotensive effects Click to Show/Hide Mechanism Graph
Could Not Find 2D Structure
      Drug Name Indapamide Nitrous acid
      Mechanism Hypotensive effects
Voltage-gated potassium channel  Blocker
Hypotensive effects
Guanylate cyclase  Agonist
      Key Mechanism Factor 1
Factor Name Voltage-gated potassium channel Kv7.1
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Structure Sequence
MAAASSPPRAERKRWGWGRLPGARRGSAGLAKKCPFSLELAEGGPAGGALYAPIAPGAPGPAPPASPAAPAAPPVASDLGPRPPVSLDPRVSIYSTRRPVLARTHVQGRVYNFLERPTGWKCFVYHFAVFLIVLVCLIFSVLSTIEQYAALATGTLFWMEIVLVVFFGTEYVVRLWSAGCRSKYVGLWGRLRFARKPISIIDLIVVVASMVVLCVGSKGQVFATSAIRGIRFLQILRMLHVDRQGGTWRLLGSVVFIHRQELITTLYIGFLGLIFSSYFVYLAEKDAVNESGRVEFGSYADALWWGVVTVTTIGYGDKVPQTWVGKTIASCFSVFAISFFALPAGILGSGFALKVQQKQRQKHFNRQIPAAASLIQTAWRCYAAENPDSSTWKIYIRKAPRSHTLLSPSPKPKKSVVVKKKKFKLDKDNGVTPGEKMLTVPHITCDPPEERRLDHFSVDGYDSSVRKSPTLLEVSMPHFMRTNSFAEDLDLEGETLLTPITHISQLREHHRATIKVIRRMQYFVAKKKFQQARKPYDVRDVIEQYSQGHLNLMVRIKELQRRLDQSIGKPSLFISVSEKSKDRGSNTIGARLNRVEDKVTQLDQRLALITDMLHQLLSLHGGSTPGSGGPPREGGAHITQPCGSGGSVDPELFLPSNTLPTYEQLTVPRRGPDEGS
Gene Name KCNQ1
Uniprot ID KCNQ1_HUMAN
KEGG Pathway hsa:3784
Protein Family Potassium channel family
Protein Function
Potassium channel that plays an important role in a number of tissues, including heart, inner ear, stomach and colon (PubMed:10646604, PubMed:25441029). Associates with KCNE beta subunits that modulates current kinetics (PubMed:9312006, PubMed:9108097, PubMed:8900283, PubMed:10646604, PubMed:11101505, PubMed:19687231). Induces a voltage-dependent current by rapidly activating and slowly deactivating potassium-selective outward current (PubMed:9312006, PubMed:9108097, PubMed:8900283, PubMed:10646604, PubMed:11101505, PubMed:25441029). Promotes also a delayed voltage activated potassium current showing outward rectification characteristic (By similarity). During beta-adrenergic receptor stimulation participates in cardiac repolarization by associating with KCNE1 to form the I(Ks) cardiac potassium current that increases the amplitude and slows down the activation kinetics of outward potassium current I(Ks) (By similarity) (PubMed:9312006, PubMed:9108097, PubMed:8900283, PubMed:10646604, PubMed:11101505). Muscarinic agonist oxotremorine-M strongly suppresses KCNQ1/KCNE1 current (PubMed:10713961). When associated with KCNE3, forms the potassium channel that is important for cyclic AMP-stimulated intestinal secretion of chloride ions (PubMed:10646604). This interaction with KCNE3 is reduced by 17beta-estradiol, resulting in the reduction of currents (By similarity). During conditions of increased substrate load, maintains the driving force for proximal tubular and intestinal sodium ions absorption, gastric acid secretion, and cAMP-induced jejunal chloride ions secretion (By similarity). Allows the provision of potassium ions to the luminal membrane of the secretory canaliculus in the resting state as well as during stimulated acid secretion (By similarity). When associated with KCNE2, forms a heterooligomer complex leading to currents with an apparently instantaneous activation, a rapid deactivation process and a linear current-voltage relationship and decreases the amplitude of the outward current (PubMed:11101505). When associated with KCNE4, inhibits voltage-gated potassium channel activity (PubMed:19687231). When associated with KCNE5, this complex only conducts current upon strong and continued depolarization (PubMed:12324418). Also forms a heterotetramer with KCNQ5; has a voltage-gated potassium channel activity (PubMed:24855057). Binds with phosphatidylinositol 4,5-bisphosphate (PubMed:25037568).
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      Key Mechanism Factor 2
Factor Name Guanylate cyclase soluble Structure Sequence
Protein Family Adenylyl cyclase class-4/guanylyl cyclase family
Protein Function
There are two types of guanylate cyclases: soluble forms and membrane-associated receptor forms. Activated by nitric oxide in the presence of magnesium or manganese ions.
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      Mechanism Description
  • Additive hypotensive effects by the combination of Indapamide and Nitrous acid 

Recommended Action
      Management Sodium nitrite should be used with caution in the presence of concomitant antihypertensive agents, diuretics, vasodilators, or PDE5 inhibitors. Hemodynamics should be monitored during and after administration of sodium nitrite, and the infusion rate decreased if significant hypotension occurs. In addition, methemoglobin levels should be monitored and oxygen administered during treatment whenever possible.

References
1 Fuhr U, Maier-Bruggemann A, Blume H, et al. "Grapefruit juice increases oral nimodipine bioavailability." Int J Clin Pharmacol Ther 36 (1998): 126-32. [PMID: 9562227]
2 Gunston GD, Mehta U "Potentially serious drug interactions with grapefruit juice." S Afr Med J 90 (2000): 41. [PMID: 10721388]
3 Product Information. Sodium Nitrite (sodium nitrite). Hope Pharmaceuticals, Scottsdale, AZ.