Drug General Information (ID: DDIUB53ZJI)
  Drug Name Sildenafil Drug Info Diazoxide Drug Info
  Drug Type Small molecule Small molecule
  Therapeutic Class Impotence Agents/Agents For Pulmonary Hypertension Antihypertensive Agents
  Structure

 Mechanism of Sildenafil-Diazoxide Interaction (Severity Level: Moderate)
     Additive hypotensive effects Click to Show/Hide Mechanism Graph
Could Not Find 2D Structure
      Drug Name Sildenafil Diazoxide
      Mechanism Hypotensive effects
Prostacyclin receptor  Agonist
Hypotensive effects
ATP-sensitive inward rectifier potassium channel  Inducer
      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.
    Click to Show/Hide
      Key Mechanism Factor 2
Factor Name Inward rectifier potassium channel Structure Sequence
Protein Family Inward rectifier-type potassium channel (TC 1.A.2.1) family
Protein Function
This receptor is controlled by G proteins. Inward rectifier potassium channels are characterized by a greater tendency to allow potassium to flow into the cell rather than out of it. Their voltage dependence is regulated by the concentration of extracellular potassium; as external potassium is raised, the voltage range of the channel opening shifts to more positive voltages. The inward rectification is mainly due to the blockage of outward current by internal magnesium. Can be blocked by extracellular barium (By similarity). Subunit of ATP-sensitive potassium channels (KATP). Can form cardiac and smooth muscle-type KATP channels with ABCC9. KCNJ11 forms the channel pore while ABCC9 is required for activation and regulation.
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      Mechanism Description
  • Additive hypotensive effects by the combination of Sildenafil and Diazoxide 

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.