Details of Drug Interaction | MecDDI

Drug General Information (ID: DDIP46YQ5M)
Drug Name			Amiloride		Drug Info		Nitrous acid		Drug Info
Drug Type		Small molecule				Small molecule
Therapeutic Class		Diuretics				Antidotes
Structure

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

Drug Name		Amiloride				Nitrous acid
Mechanism		Hypotensive effects Amiloride-sensitive sodium channel Inhibitor				Hypotensive effects Guanylate cyclase Agonist
Key Mechanism Factor 1
		Factor Name		Amiloride-sensitive sodium channel				Structure Sequence
		Protein Family		Amiloride-sensitive sodium channel (TC 1.A.6) family
		Protein Function		Sodium permeable non-voltage-sensitive ion channel inhibited by the diuretic amiloride. Mediates the electrodiffusion of the luminal sodium (and water, which follows osmotically) through the apical membrane of epithelial cells. Plays an essential role in electrolyte and blood pressure homeostasis, but also in airway surface liquid homeostasis, which is important for proper clearance of mucus. Controls the reabsorption of sodium in kidney, colon, lung and eccrine sweat glands. Also plays a role in taste perception. 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 Amiloride 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.