Details of Drug Interaction

Details of Drug-Drug Interaction

 Drug General Information (ID: DDIXD3NIGS)
  Drug Name Carvedilol Drug Info Thiothixene Drug Info
  Drug Type Small molecule Small molecule
  Therapeutic Class Vasodilator Agents Antipsychotic Agents
  Structure

 Mechanism of Carvedilol-Thiothixene Interaction (Severity Level: Moderate)
     Competitive inhibition of metabolic enzyme Click to Show/Hide Mechanism Graph
Could Not Find 2D Structure
      Drug Name Carvedilol Thiothixene
      Mechanism 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 Carvedilol and Thiothixene due to competitive inhibition of the same metabolic pathway

Recommended Action
      Management Atenolol, carteolol, or nadolol may be considered as alternatives because they undergo renal elimination and are not expected to interact. If this combination cannot be avoided, decreased dosage of either or both drugs may be necessary and the patient should be closely monitored for cardiovascular or nervous system adverse effects.

References
1 Markowitz JS, Wells BG, Carson WH "Interactions between antipsychotic and antihypertensive drugs." Ann Pharmacother 29 (1995): 603-9. [PMID: 7663034]
2 Miller F, Rampling D "Adverse effects of combined propranolol and chlorpromazine therapy." Am J Psychiatry 139 (1982): 1198-9. [PMID: 6810714]
3 Peet M, Middlemiss D, Yates R "Pharmacokinetic interaction between propranolol and chlorpromazine in schizophrenic patients." Lancet 2 (1980): 978. [PMID: 6107617]
4 Silver JM, Yudofsky SC, Kogan M, Katz BL "Elevation of thioridazine plasma levels by propranolol." Am J Psychiatry 143 (1986): 1290-2. [PMID: 3766793]
5 Vestal RE, Kornhauser DM, Hollifield JW, Shand DG "Inhibition of propranolol metabolism by chlorpromazine." Clin Pharmacol Ther 25 (1979): 19-24. [PMID: 758241]