Details of Drug Interaction

Details of Drug-Drug Interaction

 Drug General Information (ID: DDIL2V3EY9)
  Drug Name Metolazone Drug Info Nitrous acid Drug Info
  Drug Type Small molecule Small molecule
  Therapeutic Class Antihypertensive Agents Antidotes
  Structure

 Mechanism of Metolazone-Nitrous acid Interaction (Severity Level: Moderate)
     Additive hypotensive effects Click to Show/Hide Mechanism Graph
Could Not Find 2D Structure
      Drug Name Metolazone Nitrous acid
      Mechanism Hypotensive effects
Solute carrier family 12 member 3  Blocker 		Hypotensive effects
Guanylate cyclase  Agonist
      Key Mechanism Factor 1
Factor Name Solute carrier family 12 member 3
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Structure Sequence
MAELPTTETPGDATLCSGRFTISTLLSSDEPSPPAAYDSSHPSHLTHSSTFCMRTFGYNTIDVVPTYEHYANSTQPGEPRKVRPTLADLHSFLKQEGRHLHALAFDSRPSHEMTDGLVEGEAGTSSEKNPEEPVRFGWVKGVMIRCMLNIWGVILYLRLPWITAQAGIVLTWIIILLSVTVTSITGLSISAISTNGKVKSGGTYFLISRSLGPELGGSIGLIFAFANAVGVAMHTVGFAETVRDLLQEYGAPIVDPINDIRIIAVVSVTVLLAISLAGMEWESKAQVLFFLVIMVSFANYLVGTLIPPSEDKASKGFFSYRADIFVQNLVPDWRGPDGTFFGMFSIFFPSATGILAGANISGDLKDPAIAIPKGTLMAIFWTTISYLAISATIGSCVVRDASGVLNDTVTPGWGACEGLACSYGWNFTECTQQHSCHYGLINYYQTMSMVSGFAPLITAGIFGATLSSALACLVSAAKVFQCLCEDQLYPLIGFFGKGYGKNKEPVRGYLLAYAIAVAFIIIAELNTIAPIISNFFLCSYALINFSCFHASITNSPGWRPSFQYYNKWAALFGAIISVVIMFLLTWWAALIAIGVVLFLLLYVIYKKPEVNWGSSVQAGSYNLALSYSVGLNEVEDHIKNYRPQCLVLTGPPNFRPALVDFVGTFTRNLSLMICGHVLIGPHKQRMPELQLIANGHTKWLNKRKIKAFYSDVIAEDLRRGVQILMQAAGLGRMKPNILVVGFKKNWQSAHPATVEDYIGILHDAFDFNYGVCVMRMREGLNVSKMMQAHINPVFDPAEDGKEASARVDPKALVKEEQATTIFQSEQGKKTIDIYWLFDDGGLTLLIPYLLGRKRRWSKCKIRVFVGGQINRMDQERKAIISLLSKFRLGFHEVHILPDINQNPRAEHTKRFEDMIAPFRLNDGFKDEATVNEMRRDCPWKISDEEITKNRVKSLRQVRLNEIVLDYSRDAALIVITLPIGRKGKCPSSLYMAWLETLSQDLRPPVILIRGNQENVLTFYCQ
Gene Name SLC12A3
Uniprot ID S12A3_HUMAN
KEGG Pathway hsa:6559
Protein Family SLC12A transporter family
Protein Function
Electroneutral sodium and chloride ion cotransporter. In kidney distal convoluted tubules, key mediator of sodium and chloride reabsorption (PubMed:21613606, PubMed:22009145). Receptor for the pro-inflammatory cytokine IL18. Contributes to IL18-induced cytokine production, including IFNG, IL6, IL18 and CCL2. May act either independently of IL18R1, or in a complex with IL18R1 (By similarity).
    Click to Show/Hide
      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.
    Click to Show/Hide
      Mechanism Description
  • Additive hypotensive effects by the combination of Metolazone 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.