Details of Drug Interaction | MecDDI

Drug General Information (ID: DDI0YPFLOD)
Drug Name			Lofexidine		Drug Info		Nitrous acid		Drug Info
Drug Type		Small molecule				Small molecule
Therapeutic Class		Antihypertensive Agents				Antidotes
Structure

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

Drug Name		Lofexidine				Nitrous acid
Mechanism		Hypotensive effects Alpha-2 adrenergic receptor Agonist				Hypotensive effects Guanylate cyclase Agonist
Key Mechanism Factor 1
		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. 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 Lofexidine 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.