Details of Drug Interaction

Details of Drug-Drug Interaction

 Drug General Information (ID: DDITS1I7WM)
  Drug Name Sildenafil Drug Info Nitrous acid Drug Info
  Drug Type Small molecule Small molecule
  Therapeutic Class Impotence Agents/Agents For Pulmonary Hypertension Antidotes
  Structure

 Mechanism of Sildenafil-Nitrous acid Interaction (Severity Level: Moderate)
     Additive hypotensive effects Click to Show/Hide Mechanism Graph
Could Not Find 2D Structure
      Drug Name Sildenafil Nitrous acid
      Mechanism Hypotensive effects
Phosphodiesterase 5A  Inhibitor 		Hypotensive effects
Guanylate cyclase  Agonist
      Key Mechanism Factor 1
Factor Name Phosphodiesterase 5A
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Structure Sequence
MERAGPSFGQQRQQQQPQQQKQQQRDQDSVEAWLDDHWDFTFSYFVRKATREMVNAWFAERVHTIPVCKEGIRGHTESCSCPLQQSPRADNSAPGTPTRKISASEFDRPLRPIVVKDSEGTVSFLSDSEKKEQMPLTPPRFDHDEGDQCSRLLELVKDISSHLDVTALCHKIFLHIHGLISADRYSLFLVCEDSSNDKFLISRLFDVAEGSTLEEVSNNCIRLEWNKGIVGHVAALGEPLNIKDAYEDPRFNAEVDQITGYKTQSILCMPIKNHREEVVGVAQAINKKSGNGGTFTEKDEKDFAAYLAFCGIVLHNAQLYETSLLENKRNQVLLDLASLIFEEQQSLEVILKKIAATIISFMQVQKCTIFIVDEDCSDSFSSVFHMECEELEKSSDTLTREHDANKINYMYAQYVKNTMEPLNIPDVSKDKRFPWTTENTGNVNQQCIRSLLCTPIKNGKKNKVIGVCQLVNKMEENTGKVKPFNRNDEQFLEAFVIFCGLGIQNTQMYEAVERAMAKQMVTLEVLSYHASAAEEETRELQSLAAAVVPSAQTLKITDFSFSDFELSDLETALCTIRMFTDLNLVQNFQMKHEVLCRWILSVKKNYRKNVAYHNWRHAFNTAQCMFAALKAGKIQNKLTDLEILALLIAALSHDLDHRGVNNSYIQRSEHPLAQLYCHSIMEHHHFDQCLMILNSPGNQILSGLSIEEYKTTLKIIKQAILATDLALYIKRRGEFFELIRKNQFNLEDPHQKELFLAMLMTACDLSAITKPWPIQQRIAELVATEFFDQGDRERKELNIEPTDLMNREKKNKIPSMQVGFIDAICLQLYEALTHVSEDCFPLLDGCRKNRQKWQALAEQQEKMLINGESGQAKRN
Gene Name PDE5A
Uniprot ID PDE5A_HUMAN
KEGG Pathway hsa:8654
Protein Family Cyclic nucleotide phosphodiesterase family
Protein Function
Plays a role in signal transduction by regulating the intracellular concentration of cyclic nucleotides. This phosphodiesterase catalyzes the specific hydrolysis of cGMP to 5'-GMP (PubMed:9714779, PubMed:15489334). Specifically regulates nitric-oxide-generated cGMP (PubMed:15489334).
    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 Sildenafil 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.