Details of Drug Interaction

Details of Drug-Drug Interaction

 Drug General Information (ID: DDIH15LA4D)
  Drug Name Propafenone Drug Info Nebivolol Drug Info
  Drug Type Small molecule Small molecule
  Therapeutic Class Antiarrhythmic Agents Antihypertensive Agents
  Structure

 Mechanism of Propafenone-Nebivolol Interaction (Severity Level: Moderate)
     CYP450 enzyme inhibition Click to Show/Hide Mechanism Graph
Could Not Find 2D Structure
      Drug Name Propafenone Nebivolol
      Mechanism CYP450 2D6 inhibitor CYP450 2D6 substrate
      Key Mechanism Factor 1
Factor Name Cytochrome P450 2D6
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Structure Sequence
MGLEALVPLAVIVAIFLLLVDLMHRRQRWAARYPPGPLPLPGLGNLLHVDFQNTPYCFDQLRRRFGDVFSLQLAWTPVVVLNGLAAVREALVTHGEDTADRPPVPITQILGFGPRSQGVFLARYGPAWREQRRFSVSTLRNLGLGKKSLEQWVTEEAACLCAAFANHSGRPFRPNGLLDKAVSNVIASLTCGRRFEYDDPRFLRLLDLAQEGLKEESGFLREVLNAVPVLLHIPALAGKVLRFQKAFLTQLDELLTEHRMTWDPAQPPRDLTEAFLAEMEKAKGNPESSFNDENLRIVVADLFSAGMVTTSTTLAWGLLLMILHPDVQRRVQQEIDDVIGQVRRPEMGDQAHMPYTTAVIHEVQRFGDIVPLGVTHMTSRDIEVQGFRIPKGTTLITNLSSVLKDEAVWEKPFRFHPEHFLDAQGHFVKPEAFLPFSAGRRACLGEPLARMELFLFFTSLLQHFSFSVPTGQPRPSHHGVFAFLVSPSPYELCAVPR
Gene Name CYP2D6
Uniprot ID CP2D6_HUMAN
KEGG Pathway hsa:1565
Protein Family Cytochrome P450 family
Protein Function
A cytochrome P450 monooxygenase involved in the metabolism of fatty acids, steroids and retinoids (PubMed:18698000, PubMed:19965576, PubMed:20972997, PubMed:21289075, PubMed:21576599). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase) (PubMed:18698000, PubMed:19965576, PubMed:20972997, PubMed:21289075, PubMed:21576599). Catalyzes the epoxidation of double bonds of polyunsaturated fatty acids (PUFA) (PubMed:19965576, PubMed:20972997). Metabolizes endocannabinoid arachidonoylethanolamide (anandamide) to 20-hydroxyeicosatetraenoic acid ethanolamide (20-HETE-EA) and 8,9-, 11,12-, and 14,15-epoxyeicosatrienoic acid ethanolamides (EpETrE-EAs), potentially modulating endocannabinoid system signaling (PubMed:18698000, PubMed:21289075). Catalyzes the hydroxylation of carbon-hydrogen bonds. Metabolizes cholesterol toward 25-hydroxycholesterol, a physiological regulator of cellular cholesterol homeostasis (PubMed:21576599). Catalyzes the oxidative transformations of all-trans retinol to all-trans retinal, a precursor for the active form all-trans-retinoic acid (PubMed:10681376). Also involved in the oxidative metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic antidepressants.
    Click to Show/Hide
      Mechanism Description
  • Decreased metabolism of Nebivolol caused by Propafenone mediated inhibition of CYP450 enzyme

Recommended Action
      Management Patients receiving this combination should be monitored for hypotension, heart failure, bradycardia, arrhythmias, and mental status changes. Beta-blocker dosage may be decreased if necessary.

References
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13 Product Information. Blocadren (timolol). Merck & Co, Inc, West Point, PA.
14 Product Information. Brevibloc (esmolol). DuPont Pharmaceuticals, Wilmington, DE.
15 Product Information. Cartrol (carteolol). Abbott Pharmaceutical, Abbott Park, IL.
16 Product Information. Corgard (nadolol). Bristol-Myers Squibb, Princeton, NJ.
17 Product Information. Inderal (propranolol). Wyeth-Ayerst Laboratories, Philadelphia, PA.
18 Product Information. Levatol (penbutolol). Reed and Carnrick, Jersey City, NJ.
19 Product Information. Normodyne (labetalol). Schering Laboratories, Kenilworth, NJ.
20 Product Information. Rhythmol (propafenone). Knoll Pharmaceutical Company, Whippany, NJ.
21 Product Information. Tenormin (atenolol). ICN Pharmaceuticals Inc, Cost Mesa, CA.
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