Details of Drug Interaction

Details of Drug-Drug Interaction

 Drug General Information (ID: DDID4KTWJB)
  Drug Name Disopyramide Drug Info Amrinone Drug Info
  Drug Type Small molecule Small molecule
  Therapeutic Class Antiarrhythmic Agents Cardiovascular Agents
  Structure

 Mechanism of Disopyramide-Amrinone Interaction (Severity Level: Moderate)
     Additive hypotensive effects Click to Show/Hide Mechanism Graph
Could Not Find 2D Structure
      Drug Name Disopyramide Amrinone
      Mechanism Hypotensive effects
Voltage-gated sodium channel  Blocker 		Hypotensive effects
Phosphodiesterase 3  Inhibitor
      Key Mechanism Factor 1
Factor Name Voltage-gated sodium channel Structure Sequence
Protein Family Sodium channel (TC 1.A.1.10) family
Protein Function
This protein mediates the voltage-dependent sodium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a sodium-selective channel through which Na(+) ions may pass in accordance with their electrochemical gradient (PubMed:1309946, PubMed:21447824, PubMed:25370050, PubMed:23420830, PubMed:23085483, PubMed:26279430, PubMed:26392562, PubMed:26776555). It is a tetrodotoxin-resistant Na(+) channel isoform (PubMed:1309946). This channel is responsible for the initial upstroke of the action potential. Channel inactivation is regulated by intracellular calcium levels (PubMed:19074138).
    Click to Show/Hide
      Key Mechanism Factor 2
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).
    Click to Show/Hide
      Mechanism Description
  • Additive hypotensive effects by the combination of Disopyramide and Amrinone 

Recommended Action
      Management Until further data are available, it may be appropriate to closely monitor hemodynamic status during concomitant administration of these drugs. The same precaution may be applicable to milrinone based on its structural and pharmacologic similarities to inamrinone.

References
1 Fuhr U, Maier-Bruggemann A, Blume H, et al. "Grapefruit juice increases oral nimodipine bioavailability." Int J Clin Pharmacol Ther 36 (1998): 126-32. [PMID: 9562227]
2 Gunston GD, Mehta U "Potentially serious drug interactions with grapefruit juice." S Afr Med J 90 (2000): 41. [PMID: 10721388]
3 Product Information. Inocor (inamrinone). Sanofi Winthrop Pharmaceuticals, New York, NY.