Details of Drug Interaction | MecDDI

Drug General Information (ID: DDI60R5YLW)
Drug Name			Diazoxide		Drug Info		Nitrous acid		Drug Info
Drug Type		Small molecule				Small molecule
Therapeutic Class		Antihypertensive Agents				Antidotes
Structure

Mechanism of Diazoxide-Nitrous acid Interaction (Severity Level: Moderate)
Additive hypotensive effects Click to Show/Hide Mechanism Graph

Drug Name		Diazoxide				Nitrous acid
Mechanism		Hypotensive effects ATP-sensitive inward rectifier potassium channel Inducer				Hypotensive effects Guanylate cyclase Agonist
Key Mechanism Factor 1
		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
Key Mechanism Factor 2
		Factor Name		Guanylate cyclase soluble				Structure Sequence
		Protein Family		Adenylyl cyclase class-4/guanylyl cyclase family
		Protein Function		There are two types of guanylate cyclases: soluble forms and membrane-associated receptor forms. Activated by nitric oxide in the presence of magnesium or manganese ions. Click to Show/Hide
Mechanism Description		Additive hypotensive effects by the combination of Diazoxide and Nitrous acid

Recommended Action
Management		Sodium nitrite should be used with caution in the presence of concomitant antihypertensive agents, diuretics, vasodilators, or PDE5 inhibitors. Hemodynamics should be monitored during and after administration of sodium nitrite, and the infusion rate decreased if significant hypotension occurs. In addition, methemoglobin levels should be monitored and oxygen administered during treatment whenever possible.

References
1	Fuhr U, Maier-Bruggemann A, Blume H, et al. "Grapefruit juice increases oral nimodipine bioavailability." Int J Clin Pharmacol Ther 36 (1998): 126-32. [PMID: 9562227]
2	Gunston GD, Mehta U "Potentially serious drug interactions with grapefruit juice." S Afr Med J 90 (2000): 41. [PMID: 10721388]
3	Product Information. Sodium Nitrite (sodium nitrite). Hope Pharmaceuticals, Scottsdale, AZ.