Details of Drug Interaction

Details of Drug-Drug Interaction

 Drug General Information (ID: DDISP14UWM)
  Drug Name Disulfiram Drug Info Isoniazid Drug Info
  Drug Type Small molecule Small molecule
  Therapeutic Class Alcohol Deterrents Antitubercular Agents
  Structure

 Mechanism of Disulfiram-Isoniazid Interaction (Severity Level: Moderate)
     Additive dopaminergic effects Click to Show/Hide Mechanism Graph
Could Not Find 2D Structure
      Drug Name Disulfiram Isoniazid
      Mechanism Dopaminergic effects
Dopamine beta-hydroxylase  Inhibitor 		Dopaminergic effects
Monoamine oxidase non-selective  Inhibitor
      Key Mechanism Factor 1
Factor Name Dopamine beta hydroxylase
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Structure Sequence
MPALSRWASLPGPSMREAAFMYSTAVAIFLVILVAALQGSAPRESPLPYHIPLDPEGSLELSWNVSYTQEAIHFQLLVRRLKAGVLFGMSDRGELENADLVVLWTDGDTAYFADAWSDQKGQIHLDPQQDYQLLQVQRTPEGLTLLFKRPFGTCDPKDYLIEDGTVHLVYGILEEPFRSLEAINGSGLQMGLQRVQLLKPNIPEPELPSDACTMEVQAPNIQIPSQETTYWCYIKELPKGFSRHHIIKYEPIVTKGNEALVHHMEVFQCAPEMDSVPHFSGPCDSKMKPDRLNYCRHVLAAWALGAKAFYYPEEAGLAFGGPGSSRYLRLEVHYHNPLVIEGRNDSSGIRLYYTAKLRRFNAGIMELGLVYTPVMAIPPRETAFILTGYCTDKCTQLALPPSGIHIFASQLHTHLTGRKVVTVLVRDGREWEIVNQDNHYSPHFQEIRMLKKVVSVHPGDVLITSCTYNTEDRELATVGGFGILEEMCVNYVHYYPQTQLELCKSAVDAGFLQKYFHLINRFNNEDVCTCPQASVSQQFTSVPWNSFNRDVLKALYSFAPISMHCNKSSAVRFQGEWNLQPLPKVISTLEEPTPQCPTSQGRSPAGPTVVSIGGGKG
Gene Name DBH
Uniprot ID DOPO_HUMAN
KEGG Pathway hsa:1621
Protein Family Copper type II ascorbate-dependent monooxygenase family
Protein Function
Conversion of dopamine to noradrenaline.
    Click to Show/Hide
      Key Mechanism Factor 2
Factor Name Monoamine oxidase Structure Sequence
Protein Family Flavin monoamine oxidase family
Protein Function
Catalyzes the oxidative deamination of primary and some secondary amine such as neurotransmitters, with concomitant reduction of oxygen to hydrogen peroxide and has important functions in the metabolism of neuroactive and vasoactive amines in the central nervous system and peripheral tissues (PubMed:20493079, PubMed:8316221, PubMed:18391214, PubMed:24169519). Preferentially oxidizes serotonin (PubMed:20493079, PubMed:24169519). Also catalyzes the oxidative deamination of kynuramine to 3-(2-aminophenyl)-3-oxopropanal that can spontaneously condense to 4-hydroxyquinoline (By similarity).
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      Mechanism Description
  • Additive dopaminergic effects by the combination of Disulfiram and Isoniazid 

Recommended Action
      Management If these agents must be coadministered, the clinician should consider monitoring the patient closely for altered mental status (drowsiness, ataxia, mood changes or behavioral changes). Disulfiram should be discontinued or the dosage reduced if an interaction is suspected.

References
1 Whittington HG, Grey L "Possible interaction between disulfiram and isoniazid." Am J Psychiatry 125 (1969): 1725-9. [PMID: 5770196]