Drug General Information (ID: DDIQ08CK2H)
  Drug Name Sildenafil Drug Info Ambrisentan Drug Info
  Drug Type Small molecule Small molecule
  Therapeutic Class Impotence Agents/Agents For Pulmonary Hypertension Agents For Pulmonary Hypertension
  Structure

 Mechanism of Sildenafil-Ambrisentan Interaction (Severity Level: Moderate)
     Additive hypotensive effects Click to Show/Hide Mechanism Graph
Could Not Find 2D Structure
      Drug Name Sildenafil Ambrisentan
      Mechanism Hypotensive effects
Prostacyclin receptor  Agonist
Antihypertensive agent
Endothelin receptor  Antagonist
      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 Endothelin A receptor
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Structure Sequence
METLCLRASFWLALVGCVISDNPERYSTNLSNHVDDFTTFRGTELSFLVTTHQPTNLVLPSNGSMHNYCPQQTKITSAFKYINTVISCTIFIVGMVGNATLLRIIYQNKCMRNGPNALIASLALGDLIYVVIDLPINVFKLLAGRWPFDHNDFGVFLCKLFPFLQKSSVGITVLNLCALSVDRYRAVASWSRVQGIGIPLVTAIEIVSIWILSFILAIPEAIGFVMVPFEYRGEQHKTCMLNATSKFMEFYQDVKDWWLFGFYFCMPLVCTAIFYTLMTCEMLNRRNGSLRIALSEHLKQRREVAKTVFCLVVIFALCWFPLHLSRILKKTVYNEMDKNRCELLSFLLLMDYIGINLATMNSCINPIALYFVSKKFKNCFQSCLCCCCYQSKSLMTSVPMNGTSIQWKNHDQNNHNTDRSSHKDSMN
Gene Name EDNRA
Uniprot ID EDNRA_HUMAN
KEGG Pathway hsa:1909
Protein Family G-protein coupled receptor 1 family
Protein Function
Receptor for endothelin-1. Mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. The rank order of binding affinities for ET-A is: ET1 > ET2 >> ET3.
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      Mechanism Description
  • Additive hypotensive effects by the combination of Sildenafil and Ambrisentan 

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.