Details of Drug Interaction

Details of Drug-Drug Interaction

 Drug General Information (ID: DDIYC0DOL7)
  Drug Name Milrinone Drug Info Tizanidine Drug Info
  Drug Type Small molecule Small molecule
  Therapeutic Class Cardiotonic Agents Analgesics
  Structure

 Mechanism of Milrinone-Tizanidine Interaction (Severity Level: Major)
     Additive hypotensive effects Click to Show/Hide Mechanism Graph
Could Not Find 2D Structure
      Drug Name Milrinone Tizanidine
      Mechanism Hypotensive effects
Phosphodiesterase 3  Inhibitor 		Hypotensive effects
Alpha-2 adrenergic receptor  Agonist
      Key Mechanism Factor 1
Factor Name Phosphodiesterase 3 Structure Sequence
Protein Family Cyclic nucleotide phosphodiesterase family
Protein Function
Cyclic nucleotide phosphodiesterase with specificity for the second messengers cAMP and cGMP, which are key regulators of many important physiological processes (PubMed:1315035, PubMed:8695850, PubMed:8155697, PubMed:25961942). Has also activity toward cUMP (PubMed:27975297). Independently of its catalytic activity it is part of an E2/17beta-estradiol-induced pro-apoptotic signaling pathway. E2 stabilizes the PDE3A/SLFN12 complex in the cytosol, promoting the dephosphorylation of SLFN12 and activating its pro-apoptotic ribosomal RNA/rRNA ribonuclease activity. This apoptotic pathway might be relevant in tissues with high concentration of E2 and be for instance involved in placenta remodeling (PubMed:31420216, PubMed:34707099).
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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 Milrinone 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.