Details of Drug Interaction | MecDDI

Drug General Information (ID: DDI5VWYM8I)
Drug Name			Phentolamine		Drug Info		Avanafil		Drug Info
Drug Type		Small molecule				Small molecule
Therapeutic Class		Antihypertensive Agents				Impotence Agents
Structure

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

Drug Name		Phentolamine				Avanafil
Mechanism		Antihypertensive agent Alpha-1 adrenergic receptor Antagonist				Hypotensive effects Phosphodiesterase 5A Inhibitor
Key Mechanism Factor 1
		Factor Name		Adrenergic receptor alpha-1				Structure Sequence
		Protein Family		G-protein coupled receptor 1 family
		Protein Function		This alpha-adrenergic receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. Its effect is mediated by G(q) and G(11) proteins. Nuclear ADRA1A-ADRA1B heterooligomers regulate phenylephrine(PE)-stimulated ERK signaling in cardiac myocytes. Click to Show/Hide
Key Mechanism Factor 2
		Factor Name		Phosphodiesterase 5A				× Structure Sequence MERAGPSFGQQRQQQQPQQQKQQQRDQDSVEAWLDDHWDFTFSYFVRKATREMVNAWFAERVHTIPVCKEGIRGHTESCSCPLQQSPRADNSAPGTPTRKISASEFDRPLRPIVVKDSEGTVSFLSDSEKKEQMPLTPPRFDHDEGDQCSRLLELVKDISSHLDVTALCHKIFLHIHGLISADRYSLFLVCEDSSNDKFLISRLFDVAEGSTLEEVSNNCIRLEWNKGIVGHVAALGEPLNIKDAYEDPRFNAEVDQITGYKTQSILCMPIKNHREEVVGVAQAINKKSGNGGTFTEKDEKDFAAYLAFCGIVLHNAQLYETSLLENKRNQVLLDLASLIFEEQQSLEVILKKIAATIISFMQVQKCTIFIVDEDCSDSFSSVFHMECEELEKSSDTLTREHDANKINYMYAQYVKNTMEPLNIPDVSKDKRFPWTTENTGNVNQQCIRSLLCTPIKNGKKNKVIGVCQLVNKMEENTGKVKPFNRNDEQFLEAFVIFCGLGIQNTQMYEAVERAMAKQMVTLEVLSYHASAAEEETRELQSLAAAVVPSAQTLKITDFSFSDFELSDLETALCTIRMFTDLNLVQNFQMKHEVLCRWILSVKKNYRKNVAYHNWRHAFNTAQCMFAALKAGKIQNKLTDLEILALLIAALSHDLDHRGVNNSYIQRSEHPLAQLYCHSIMEHHHFDQCLMILNSPGNQILSGLSIEEYKTTLKIIKQAILATDLALYIKRRGEFFELIRKNQFNLEDPHQKELFLAMLMTACDLSAITKPWPIQQRIAELVATEFFDQGDRERKELNIEPTDLMNREKKNKIPSMQVGFIDAICLQLYEALTHVSEDCFPLLDGCRKNRQKWQALAEQQEKMLINGESGQAKRN
		Gene Name		PDE5A
		Uniprot ID		PDE5A_HUMAN
		KEGG Pathway		hsa:8654
		Protein Family		Cyclic nucleotide phosphodiesterase family
		Protein Function		Plays a role in signal transduction by regulating the intracellular concentration of cyclic nucleotides. This phosphodiesterase catalyzes the specific hydrolysis of cGMP to 5'-GMP (PubMed:9714779, PubMed:15489334). Specifically regulates nitric-oxide-generated cGMP (PubMed:15489334). Click to Show/Hide
Mechanism Description		Additive hypotensive effects by the combination of Phentolamine and Avanafil

Recommended Action
Management		Caution is advised if avanafil is used in combination with alpha blockers. Patients who demonstrate hemodynamic instability on alpha blocker therapy alone are at increased risk of symptomatic hypotension with concomitant use of avanafil. Therefore, patients should be stable on alpha blocker therapy prior to initiating avanafil, and avanafil should be initiated at the lowest recommended dosage of 50 mg. In those patients already on an optimized dosage of avanafil, alpha blocker therapy should be initiated at the lowest dosage. The safety of avanafil in combination with alpha blockers may also be affected by other variables such as intravascular volume depletion and use of other antihypertensive medications.

References
1	Product Information. Cialis (tadalafil). Lilly, Eli and Company, Indianapolis, IN.
2	Product Information. Stendra (avanafil). Vivus Inc, Mountain View, CA.