Details of Drug Interaction | MecDDI

Drug General Information (ID: DDIW9J23LT)
Drug Name			Minoxidil		Drug Info		Guanethidine		Drug Info
Drug Type		Small molecule				Small molecule
Therapeutic Class		Antihypertensive Agents				Antihypertensive Agents
Structure

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

Drug Name		Minoxidil				Guanethidine
Mechanism 1		Hypotensive effects ATP-sensitive inward rectifier potassium channel Inducer				Antihypertensive agent
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
Mechanism Description		Additive hypotensive effects by the combination of Minoxidil and Guanethidine
Mechanism 2		Hypotensive effects ATP-sensitive inward rectifier potassium channel Inducer				Hypotensive effects
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 Minoxidil and Guanethidine

Recommended Action
Management		This combination should be avoided, and guanethidine or guanadrel should be discontinued, if possible, at least a week before minoxidil is started. If coadministration is necessary, the patient should be hospitalized or carefully monitored during the first week until there are no signs or symptoms of orthostasis or hypotension.

References
1	Product Information. Loniten (minoxidil). Pharmacia and Upjohn, Kalamazoo, MI.
2	Miller DD, Love DW "Drug therapy reviews: evaluation of minoxidil." Am J Hosp Pharm 37 (1980): 808-14.[PMID: 6994495]