Drug General Information (ID: DDIXFTEJ9Z)
  Drug Name Sildenafil Drug Info Treprostinil Drug Info
  Drug Type Small molecule Small molecule
  Therapeutic Class Impotence Agents/Agents For Pulmonary Hypertension Antihypertensive Agents
  Structure

 Mechanism of Sildenafil-Treprostinil Interaction (Severity Level: Moderate)
     Additive hypotensive effects Click to Show/Hide Mechanism Graph
Could Not Find 2D Structure
      Drug Name Sildenafil Treprostinil
      Mechanism Hypotensive effects
Prostacyclin receptor  Agonist
Antihypertensive agent
Prostaglandin receptor  Agonist
      Key Mechanism Factor 1
Factor Name Prostacyclin receptor
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Structure Sequence
MADSCRNLTYVRGSVGPATSTLMFVAGVVGNGLALGILSARRPARPSAFAVLVTGLAATDLLGTSFLSPAVFVAYARNSSLLGLARGGPALCDAFAFAMTFFGLASMLILFAMAVERCLALSHPYLYAQLDGPRCARLALPAIYAFCVLFCALPLLGLGQHQQYCPGSWCFLRMRWAQPGGAAFSLAYAGLVALLVAAIFLCNGSVTLSLCRMYRQQKRHQGSLGPRPRTGEDEVDHLILLALMTVVMAVCSLPLTIRCFTQAVAPDSSSEMGDLLAFRFYAFNPILDPWVFILFRKAVFQRLKLWVCCLCLGPAHGDSQTPLSQLASGRRDPRAPSAPVGKEGSCVPLSAWGEGQVEPLPPTQQSSGSAVGTSSKAEASVACSLC
Gene Name PTGIR
Uniprot ID PI2R_HUMAN
KEGG Pathway hsa:5739
Protein Family G-protein coupled receptor 1 family
Protein Function
Receptor for prostacyclin (prostaglandin I2 or PGI2). The activity of this receptor is mediated by G(s) proteins which activate adenylate cyclase.
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      Key Mechanism Factor 2
Factor Name Prostaglandin D2 receptor
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Structure Sequence
MKSPFYRCQNTTSVEKGNSAVMGGVLFSTGLLGNLLALGLLARSGLGWCSRRPLRPLPSVFYMLVCGLTVTDLLGKCLLSPVVLAAYAQNRSLRVLAPALDNSLCQAFAFFMSFFGLSSTLQLLAMALECWLSLGHPFFYRRHITLRLGALVAPVVSAFSLAFCALPFMGFGKFVQYCPGTWCFIQMVHEEGSLSVLGYSVLYSSLMALLVLATVLCNLGAMRNLYAMHRRLQRHPRSCTRDCAEPRADGREASPQPLEELDHLLLLALMTVLFTMCSLPVIYRAYYGAFKDVKEKNRTSEEAEDLRALRFLSVISIVDPWIFIIFRSPVFRIFFHKIFIRPLRYRSRCSNSTNMESSL
Gene Name PTGDR
Uniprot ID PD2R_HUMAN
KEGG Pathway hsa:5729
Protein Family G-protein coupled receptor 1 family
Protein Function
Receptor for prostaglandin D2 (PGD2). The activity of this receptor is mainly mediated by G(s) proteins that stimulate adenylate cyclase, resulting in an elevation of intracellular cAMP. A mobilization of calcium is also observed, but without formation of inositol 1,4,5-trisphosphate (By similarity). Involved in PLA2G3-dependent maturation of mast cells. PLA2G3 is secreted by immature mast cells and acts on nearby fibroblasts upstream to PTDGS to synthesize PGD2, which in turn promotes mast cell maturation and degranulation via PTGDR (By similarity).
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      Mechanism Description
  • Additive hypotensive effects by the combination of Sildenafil and Treprostinil 

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.