Details of Drug Interaction

Details of Drug-Drug Interaction

 Drug General Information (ID: DDIP14O0KM)
  Drug Name Tizanidine Drug Info Fenoldopam Drug Info
  Drug Type Small molecule Small molecule
  Therapeutic Class Analgesics Antihypertensive Agents
  Structure

 Mechanism of Tizanidine-Fenoldopam Interaction (Severity Level: Major)
     Additive hypotensive effects Click to Show/Hide Mechanism Graph
Could Not Find 2D Structure
      Drug Name Tizanidine Fenoldopam
      Mechanism Hypotensive effects
Alpha-2 adrenergic receptor  Agonist 		Hypotensive effects
Alpha-1 adrenergic receptor  Antagonist
      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.
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      Key Mechanism Factor 2
Factor Name Adrenergic receptor alpha-1 Structure Sequence
Protein Family G-protein coupled receptor 1 family
Protein Function
This alpha-adrenergic receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. Its effect is mediated by G(q) and G(11) proteins. Nuclear ADRA1A-ADRA1B heterooligomers regulate phenylephrine(PE)-stimulated ERK signaling in cardiac myocytes.
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      Mechanism Description
  • Additive hypotensive effects by the combination of Tizanidine and Fenoldopam 

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.