Details of Drug Interaction

Details of Drug-Drug Interaction

 Drug General Information (ID: DDIX9S64Y1)
  Drug Name Esmolol Drug Info Bupivacaine Drug Info
  Drug Type Small molecule Small molecule
  Therapeutic Class Antihypertensive Agents Anesthetics
  Structure

 Mechanism of Esmolol-Bupivacaine Interaction (Severity Level: Moderate)
     Competitive inhibition of metabolic enzyme Click to Show/Hide Mechanism Graph
Could Not Find 2D Structure
      Drug Name Esmolol Bupivacaine
      Mechanism 1 CYP450 2D6 substrate 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
  • Increased plasma concentrations of Esmolol and Bupivacaine due to competitive inhibition of the same metabolic pathway
     Increased risk of bradycardia Click to Show/Hide Mechanism Graph
Could Not Find 2D Structure
      Drug Name Esmolol Bupivacaine
      Mechanism 2 Bradycardia Bradycardia
      Key Mechanism Factor 2
Factor Name Bradycardia
Factor Description Bradycardia is a slow heart rate in which the heart beats less than 60 times per minute. If the heart rate is very slow and the heart is not pumping enough oxygen-rich blood to the body, and you may feel dizzy, very tired or weak, and short of breath.
      Mechanism Description
  • Increased risk of bradycardia by the combination of Esmolol and Bupivacaine 

Recommended Action
      Management Caution is recommended if multiple doses of bupivacaine are administered in the presence of a beta-blocker. Monitoring for drowsiness, mental status changes, convulsions, ECG changes, and hypotension is advisable during concurrent therapy.

References
1 Ponten J, Biber B, Bjuro T, Henriksson BA, Hjalmarson A, Lundberg D "Beta-receptor blockade and spinal anaesthesia. Withdrawal versus continuation of long-term therapy." Acta Anaesthesiol Scand Suppl 76 (1982): 62-9
2 Roitman K, Sprung J, Wallace M, Matjasko J "Enhancement of bupivacaine cardiotoxcity with cardiac glycosides and beta-adrenergic blockers: a case report." Anesth Analg 76 (1993): 658-61
3 Ponten J, Biber B, Henriksson BA, Jonsteg C "Bupivacaine for intercostal nerve blockade in patients on long-term beta-receptor blocking therapy." Acta Anaesthesiol Scand Suppl 76 (1982): 70-7