Drug General Information (ID: DDIFDNMBKC)
  Drug Name Ethanol Drug Info Cefotetan Drug Info
  Drug Type Small molecule Small molecule
  Therapeutic Class Analgesics Antibiotics
  Structure

 Mechanism of Ethanol-Cefotetan Interaction (Severity Level: Moderate)
     Non-CYP450 enzyme inhibition Click to Show/Hide Mechanism Graph
Could Not Find 2D Structure
      Drug Name Ethanol Cefotetan
      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 Cefotetan mediated inhibition of non-CYP450 enzyme

Recommended Action
      Management Patients receiving cephalosporins with the NMTT side chain should avoid the concomitant use of alcohol and alcohol-containing products.

References
1 Brown KR, Guglielmo BJ, Pons VG, Jacobs RA "Theophylline elixir, moxalactam, and a disulfiram reaction." Ann Intern Med 97 (1982): 621-2. [PMID: 6214982]
2 Foster TS, Raehl CL, Wilson HD "Disulfiram-like reaction associated with a parenteral cephalosporin." Am J Hosp Pharm 37 (1980): 858-9. [PMID: 6446854]
3 Freundt KJ, Kitson TM "Inactivation of aldehyde dehydrogenase by a putative metabolite of cefamandole." Infection 14 (1986): 44-7. [PMID: 3957436]
4 Freundt KJ, Schreiner E, Christmann-Kleiss U "Cefamandole: a competitive inhibitor of aldehyde dehydrogenase." Infection 13 (1985): 91. [PMID: 3997257]
5 Kline SS, Mauro VF, Forney RB Jr, et al "Cefotetan-induced disulfiram-type reactions and hypoprothrombinemia." Antimicrob Agents Chemother 31 (1987): 1328-31. [PMID: 3479045]
6 McMahon FG "Disulfiram-like reaction to a cephalosporin." JAMA 243 (1980): 2397. [PMID: 6445429]
7 McMahon FG, Ryan JR, Jain AK, LaCorte W, Ginzler F "Absence of disulfiram-type reactions to single and multiple doses of cefonicid: a placebo-controlled study." J Antimicrob Chemother 20 (1987): 913-8. [PMID: 3440774]
8 Reeves DS, Davies AJ "Antabuse effect with cephalosporins." Lancet 2 (1980): 540. [PMID: 6105591]
9 Umeda S, Arai T "Disulfiram-like reaction to moxalactam after celiac plexus alcohol block." Anesth Analg 64 (1985): 377. [PMID: 3977101]