Details of Drug Interaction

Details of Drug-Drug Interaction

 Drug General Information (ID: DDI3FIZT4G)
  Drug Name Minoxidil Drug Info Tizanidine Drug Info
  Drug Type Small molecule Small molecule
  Therapeutic Class Antihypertensive Agents Analgesics
  Structure

 Mechanism of Minoxidil-Tizanidine Interaction (Severity Level: Major)
     Additive hypotensive effects Click to Show/Hide Mechanism Graph
Could Not Find 2D Structure
      Drug Name Minoxidil Tizanidine
      Mechanism Hypotensive effects
ATP-sensitive inward rectifier potassium channel  Inducer 		Hypotensive effects
Alpha-2 adrenergic receptor  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.
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      Key Mechanism Factor 2
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.
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      Mechanism Description
  • Additive hypotensive effects by the combination of Minoxidil and Tizanidine 

Recommended Action
      Management A lower initial dosage and cautious dosage titration should be considered when tizanidine is initiated in patients receiving hypotensive medications. Although single doses of less than 8 mg of tizanidine have not been shown effective for spasticity in controlled clinical studies, it may be prudent to initiate treatment with 4 mg doses and gradually increase in 2 to 4 mg increments until optimum effect is achieved. The dose can be repeated at 6 to 8 hour intervals as needed, up to a maximum of three doses in 24 hours and a total daily dosage of 36 mg. However, experience with single doses exceeding 8 mg and daily doses exceeding 24 mg is limited. Close monitoring for development of hypotension is recommended.

References
1 Product Information. Zanaflex (tizanidine). Acorda Therapeutics, Hawthorne, NY.