Drug General Information (ID: DDI5ODIKB6)
  Drug Name Sildenafil Drug Info Clonidine Drug Info
  Drug Type Small molecule Small molecule
  Therapeutic Class Impotence Agents/Agents For Pulmonary Hypertension Antihypertensive Agents
  Structure

 Mechanism of Sildenafil-Clonidine Interaction (Severity Level: Moderate)
     Additive hypotensive effects Click to Show/Hide Mechanism Graph
Could Not Find 2D Structure
      Drug Name Sildenafil Clonidine
      Mechanism Hypotensive effects
Prostacyclin receptor  Agonist
Antihypertensive agent
Alpha-2 adrenergic 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.
    Click to Show/Hide
      Key Mechanism Factor 2
Factor Name Adrenergic receptor alpha-2 Structure Sequence
Protein Family G-protein coupled receptor 1 family
Protein Function
Alpha-2 adrenergic receptors mediate the catecholamine-induced inhibition of adenylate cyclase through the action of G proteins. The rank order of potency for agonists of this receptor is oxymetazoline > clonidine > epinephrine > norepinephrine > phenylephrine > dopamine > p-synephrine > p-tyramine > serotonin = p-octopamine. For antagonists, the rank order is yohimbine > phentolamine = mianserine > chlorpromazine = spiperone = prazosin > propanolol > alprenolol = pindolol.
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      Mechanism Description
  • Additive hypotensive effects by the combination of Sildenafil and Clonidine 

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.