Drug General Information (ID: DDIFT7MG0E)
  Drug Name Ethanol Drug Info Metronidazole (topical) Drug Info
  Drug Type Small molecule Small molecule
  Therapeutic Class Analgesics Antiinfective Agents
  Structure

 Mechanism of Ethanol-Metronidazole (topical) Interaction (Severity Level: Moderate)
     Non-CYP450 enzyme inhibition Click to Show/Hide Mechanism Graph
Could Not Find 2D Structure
      Drug Name Ethanol Metronidazole (topical)
      Mechanism Aldehyde dehydrogenase substrate Aldehyde dehydrogenase inhibitor
      Key Mechanism Factor 1
Factor Name Aldehyde dehydrogenase 1
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Structure Sequence
MSSSGTPDLPVLLTDLKIQYTKIFINNEWHDSVSGKKFPVFNPATEEELCQVEEGDKEDVDKAVKAARQAFQIGSPWRTMDASERGRLLYKLADLIERDRLLLATMESMNGGKLYSNAYLNDLAGCIKTLRYCAGWADKIQGRTIPIDGNFFTYTRHEPIGVCGQIIPWNFPLVMLIWKIGPALSCGNTVVVKPAEQTPLTALHVASLIKEAGFPPGVVNIVPGYGPTAGAAISSHMDIDKVAFTGSTEVGKLIKEAAGKSNLKRVTLELGGKSPCIVLADADLDNAVEFAHHGVFYHQGQCCIAASRIFVEESIYDEFVRRSVERAKKYILGNPLTPGVTQGPQIDKEQYDKILDLIESGKKEGAKLECGGGPWGNKGYFVQPTVFSNVTDEMRIAKEEIFGPVQQIMKFKSLDDVIKRANNTFYGLSAGVFTKDIDKAITISSALQAGTVWVNCYGVVSAQCPFGGFKMSGNGRELGEYGFHEYTEVKTVTVKISQKNS
Gene Name ALDH1A1
Uniprot ID AL1A1_HUMAN
KEGG Pathway hsa:216
Protein Family Aldehyde dehydrogenase family
Protein Function
Cytosolic dehydrogenase that catalyzes the irreversible oxidation of a wide range of aldehydes to their corresponding carboxylic acid (PubMed:19296407, PubMed:12941160, PubMed:15623782, PubMed:17175089, PubMed:26373694, PubMed:25450233). Functions downstream of retinol dehydrogenases and catalyzes the oxidation of retinaldehyde into retinoic acid, the second step in the oxidation of retinol/vitamin A into retinoic acid (By similarity). This pathway is crucial to control the levels of retinol and retinoic acid, two important molecules which excess can be teratogenic and cytotoxic (By similarity). Also oxidizes aldehydes resulting from lipid peroxidation like (E)-4-hydroxynon-2-enal/HNE, malonaldehyde and hexanal that form protein adducts and are highly cytotoxic. By participating for instance to the clearance of (E)-4-hydroxynon-2-enal/HNE in the lens epithelium prevents the formation of HNE-protein adducts and lens opacification (PubMed:19296407, PubMed:12941160, PubMed:15623782). Functions also downstream of fructosamine-3-kinase in the fructosamine degradation pathway by catalyzing the oxidation of 3-deoxyglucosone, the carbohydrate product of fructosamine 3-phosphate decomposition, which is itself a potent glycating agent that may react with lysine and arginine side-chains of proteins (PubMed:17175089). Has also an aminobutyraldehyde dehydrogenase activity and is probably part of an alternative pathway for the biosynthesis of GABA/4-aminobutanoate in midbrain, thereby playing a role in GABAergic synaptic transmission (By similarity).
    Click to Show/Hide
      Mechanism Description
  • Decreased metabolism of Ethanol caused by Metronidazole (topical) mediated inhibition of non-CYP450 enzyme

Recommended Action
      Management Because clear evidence is lacking concerning the safety of ethanol use during nitroimidazole therapy, patients should be apprised of the potential for interaction and instructed to avoid alcoholic beverages and products containing alcohol or propylene glycol while using oral, intravenous, or vaginal preparations of a nitroimidazole. Alcoholic beverages should not be consumed for up to 3 days after completion of systemic nitroimidazole therapy.

References
1 Harries DP, Teale KF, Sunderland G "Metronidazole and alcohol: potential problems." Scott Med J 35 (1990): 179-80. [PMID: 2077651]
2 Krulewitch CJ "An unexpected adverse drug effect." J Midwifery Womens Health 48 (2003): 67-8. [PMID: 12589307]
3 Visapaa JP, Tillonen JS, Kaihovaara PS, Salaspuro MP "Lack of disulfiram-like reaction with metronidazole and ethanol." Ann Pharmacother 36 (2002): 971-4. [PMID: 12022894]