Details of Drug Interaction

Details of Drug-Drug Interaction

 Drug General Information (ID: DDIDYCARQU)
  Drug Name Trifluoperazine Drug Info Lofexidine Drug Info
  Drug Type Small molecule Small molecule
  Therapeutic Class Antipsychotic Agents Antihypertensive Agents
  Structure

 Mechanism of Trifluoperazine-Lofexidine Interaction (Severity Level: Moderate)
     Additive hypotensive effects Click to Show/Hide Mechanism Graph
Could Not Find 2D Structure
      Drug Name Trifluoperazine Lofexidine
      Mechanism 1 Hypotensive effects
Calmodulin  Inhibitor 		Hypotensive effects
Alpha-2 adrenergic receptor  Agonist
      Key Mechanism Factor 1
Factor Name Calmodulin-1
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Structure Sequence
MADQLTEEQIAEFKEAFSLFDKDGDGTITTKELGTVMRSLGQNPTEAELQDMINEVDADGNGTIDFPEFLTMMARKMKDTDSEEEIREAFRVFDKDGNGYISAAELRHVMTNLGEKLTDEEVDEMIREADIDGDGQVNYEEFVQMMTAK
Gene Name CALM1
Uniprot ID CALM1_HUMAN
KEGG Pathway hsa:801
Protein Family Calmodulin family
Protein Function
Calmodulin mediates the control of a large number of enzymes, ion channels, aquaporins and other proteins through calcium-binding. Among the enzymes to be stimulated by the calmodulin-calcium complex are a number of protein kinases and phosphatases. Together with CCP110 and centrin, is involved in a genetic pathway that regulates the centrosome cycle and progression through cytokinesis (PubMed:16760425). Is a regulator of voltage-dependent L-type calcium channels (PubMed:31454269). Mediates calcium-dependent inactivation of CACNA1C (PubMed:26969752). Positively regulates calcium-activated potassium channel activity of KCNN2 (PubMed:27165696). Forms a potassium channel complex with KCNQ1 and regulates electrophysiological activity of the channel via calcium-binding (PubMed:25441029). Acts as a sensor to modulate the endoplasmic reticulum contacts with other organelles mediated by VMP1:ATP2A2 (PubMed:28890335).
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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.
    Click to Show/Hide
      Mechanism Description
  • Additive hypotensive effects by the combination of Trifluoperazine and Lofexidine 
     Increased risk of prolong QT interval Click to Show/Hide Mechanism Graph
Could Not Find 2D Structure
      Drug Name Trifluoperazine Lofexidine
      Mechanism 2 Prolong QT interval Prolong QT interval
      Key Mechanism Factor 3
Factor Name QT interval
Factor Description Long QT syndrome is a heart signaling disorder that can cause a fast, chaotic heartbeat (arrhythmia). Many people may not exhibit symptoms, and usually the condition is detected during routine medical tests. In others, the most common symptoms include: sudden fainting, palpitations, dizziness, seizures, sudden death.
      Mechanism Description
  • Increased risk of prolong QT interval by the combination of Trifluoperazine and Lofexidine 

Recommended Action
      Management Caution is recommended if lofexidine is used in combination with other drugs that can prolong the QT interval. Periodic monitoring with on-treatment electrocardiograms and serum electrolytes (magnesium, potassium) should be considered. Patients should be advised to seek prompt medical attention if they experience symptoms that could indicate the occurrence of torsade de pointes such as dizziness, lightheadedness, fainting, palpitation, irregular heart rhythm, shortness of breath, or syncope.

References
1 Canadian Pharmacists Association.
2 Cerner Multum, Inc. "Australian Product Information.".
3 Cerner Multum, Inc. "UK Summary of Product Characteristics.".
4 Product Information. Lucemyra (lofexidine). US WorldMeds LLC, Louisville , KY.
5 EMA. European Medicines Agency. European Union "EMA - List of medicines under additional monitoring.".