Details of Drug Interaction | MecDDI

Drug General Information (ID: DDIGRHPN5C)
Drug Name			Sildenafil		Drug Info		Minoxidil		Drug Info
Drug Type		Small molecule				Small molecule
Therapeutic Class		Impotence Agents/Agents For Pulmonary Hypertension				Antihypertensive Agents
Structure

Mechanism of Sildenafil-Minoxidil Interaction (Severity Level: Moderate)
Additive hypotensive effects Click to Show/Hide Mechanism Graph

Drug Name		Sildenafil				Minoxidil
Mechanism		Hypotensive effects Prostacyclin receptor Agonist				Antihypertensive agent ATP-sensitive inward rectifier potassium channel Inducer
Key Mechanism Factor 1
		Factor Name		Prostacyclin receptor				× 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. Click to Show/Hide
Mechanism Description		Additive hypotensive effects by the combination of Sildenafil and Minoxidil

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.