Drug General Information (ID: DDIBDVPE5T)
  Drug Name Nitroprusside Drug Info Tadalafil Drug Info
  Drug Type Small molecule Small molecule
  Therapeutic Class Antihypertensive Agents Impotence Agents
  Structure

 Mechanism of Nitroprusside-Tadalafil Interaction (Severity Level: Major)
     Additive hypotensive effects Click to Show/Hide Mechanism Graph
Could Not Find 2D Structure
      Drug Name Nitroprusside Tadalafil
      Mechanism Hypotensive effects
Guanylate cyclase  Agonist
Hypotensive effects
Phosphodiesterase 5A  Inhibitor
      Key Mechanism Factor 1
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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      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 Nitroprusside and Tadalafil 

Recommended Action
      Management The use of PDE5 inhibitors in patients receiving organic nitrates or other nitric oxide donors, either regularly or intermittently, is considered contraindicated. A suitable time interval following sildenafil or vardenafil use for the safe administration of nitrates has not been determined. For patients treated with avanafil or tadalafil, at least 12 hours after the last dose of avanafil and 48 hours after the last dose of tadalafil are recommended before nitrate administration, should it be deemed medically necessary in a life-threatening situation. Even then, nitrates should only be administered under close medical supervision with appropriate hemodynamic monitoring. Patients should be advised to seek immediate medical attention if they experience anginal chest pain after taking a PDE5 inhibitor.

References
1 Product Information. Cialis (tadalafil). Lilly, Eli and Company, Indianapolis, IN.
2 Product Information. Levitra (vardenafil). Bayer, West Haven, CT.
3 Product Information. Viagra (sildenafil). Pfizer US Pharmaceuticals, New York, NY.