Drug General Information (ID: DDILSE9Q4I)
  Drug Name Valsartan Drug Info Avanafil Drug Info
  Drug Type Small molecule Small molecule
  Therapeutic Class Antihypertensive Agents Impotence Agents
  Structure

 Mechanism of Valsartan-Avanafil Interaction (Severity Level: Moderate)
     Additive hypotensive effects Click to Show/Hide Mechanism Graph
Could Not Find 2D Structure
      Drug Name Valsartan Avanafil
      Mechanism Antihypertensive agent
Amiloride-sensitive sodium channel  Blocker
Hypotensive effects
Phosphodiesterase 5A  Inhibitor
      Key Mechanism Factor 1
Factor Name Amiloride-sensitive sodium channel Structure Sequence
Protein Family Amiloride-sensitive sodium channel (TC 1.A.6) family
Protein Function
Sodium permeable non-voltage-sensitive ion channel inhibited by the diuretic amiloride. Mediates the electrodiffusion of the luminal sodium (and water, which follows osmotically) through the apical membrane of epithelial cells. Plays an essential role in electrolyte and blood pressure homeostasis, but also in airway surface liquid homeostasis, which is important for proper clearance of mucus. Controls the reabsorption of sodium in kidney, colon, lung and eccrine sweat glands. Also plays a role in taste perception.
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      Key Mechanism Factor 2
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).
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      Mechanism Description
  • Additive hypotensive effects by the combination of Valsartan and Avanafil 

Recommended Action
      Management Caution is advised if PDE5 inhibitors are prescribed in combination with antihypertensive agents. Patients receiving the combination should be advised to avoid rising abruptly from a sitting or recumbent position, especially following treatment initiation or a dosage increase, and to contact their doctor if they experience symptoms of hypotension such as dizziness, lightheadedness, fainting, or tachycardia.

References
1 Product Information. Levitra (vardenafil). Bayer, West Haven, CT.
2 Product Information. Stendra (avanafil). Vivus Inc, Mountain View, CA.
3 Product Information. Viagra (sildenafil). Pfizer US Pharmaceuticals, New York, NY.