Details of Drug Interaction

Details of Drug-Drug Interaction

 Drug General Information (ID: DDI6ICPL7E)
  Drug Name Tacrine Drug Info Cimetidine Drug Info
  Drug Type Small molecule Small molecule
  Therapeutic Class Parasympathomimetics Antiulcer Agents
  Structure

 Mechanism of Tacrine-Cimetidine Interaction (Severity Level: Moderate)
     Antagonize the effect of cholinergic agents Click to Show/Hide Mechanism Graph
Could Not Find 2D Structure
      Drug Name Tacrine Cimetidine
      Mechanism Cholinergic effects
Acetylcholinesterase  Inhibitor 		Anticholinergic effects
Acetylcholine receptor  Antagonist
      Key Mechanism Factor 1
Factor Name Acetylcholinesterase
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Structure Sequence
MRPPQCLLHTPSLASPLLLLLLWLLGGGVGAEGREDAELLVTVRGGRLRGIRLKTPGGPVSAFLGIPFAEPPMGPRRFLPPEPKQPWSGVVDATTFQSVCYQYVDTLYPGFEGTEMWNPNRELSEDCLYLNVWTPYPRPTSPTPVLVWIYGGGFYSGASSLDVYDGRFLVQAERTVLVSMNYRVGAFGFLALPGSREAPGNVGLLDQRLALQWVQENVAAFGGDPTSVTLFGESAGAASVGMHLLSPPSRGLFHRAVLQSGAPNGPWATVGMGEARRRATQLAHLVGCPPGGTGGNDTELVACLRTRPAQVLVNHEWHVLPQESVFRFSFVPVVDGDFLSDTPEALINAGDFHGLQVLVGVVKDEGSYFLVYGAPGFSKDNESLISRAEFLAGVRVGVPQVSDLAAEAVVLHYTDWLHPEDPARLREALSDVVGDHNVVCPVAQLAGRLAAQGARVYAYVFEHRASTLSWPLWMGVPHGYEIEFIFGIPLDPSRNYTAEEKIFAQRLMRYWANFARTGDPNEPRDPKAPQWPPYTAGAQQYVSLDLRPLEVRRGLRAQACAFWNRFLPKLLSATDTLDEAERQWKAEFHRWSSYMVHWKNQFDHYSKQDRCSDL
Gene Name ACHE
Uniprot ID ACES_HUMAN
KEGG Pathway hsa:43
Protein Family Type-B carboxylesterase/lipase family
Protein Function
Hydrolyzes rapidly the acetylcholine neurotransmitter released into the synaptic cleft allowing to terminate the signal transduction at the neuromuscular junction. Role in neuronal apoptosis.
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      Key Mechanism Factor 2
Factor Name Muscarinic acetylcholine receptor M Structure Sequence
Protein Family G-protein coupled receptor 1 family
Protein Function
The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins. Primary transducing effect is Pi turnover.
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      Mechanism Description
  • Antagonize the effect of Tacrine when combined with Cimetidine 

Recommended Action
      Management Drugs that possess anticholinergic activity such as cimetidine should generally be avoided in patients with Alzheimer's disease or other cognitive impairment, regardless of whether they are receiving an acetylcholinesterase inhibitor. Famotidine or nizatidine may be suitable alternatives if an H2-receptor antagonist is necessary. In patients who are already receiving an acetylcholinesterase inhibitor with cimetidine, every attempt should be made to discontinue the latter. Caution is required, however, since anticholinergic withdrawal may occur. Seizures have been reported following abrupt discontinuation of anticholinergics during acetylcholinesterase inhibitor therapy.

References
1 Beers MH, Ouslander JG, Rollingher I, Reuben DB, Brooks J, Beck JC "Explicit criteria for determining inappropriate medication use in nursing home residents." Arch Intern Med 151 (1991): 1825-32. [PMID: 1888249]
2 Carnahan RM, Lund BC, Perry PJ, Chrischilles EA "The concurrent use of anticholinergics and cholinesterase inhibitors: rare event or common practice?" J Am Geriatr Soc 52 (2004): 2082-7. [PMID: 15571547]
3 Fick DM, Cooper JW, Wade WE, Waller JL, Maclean JR, Beers MH "Updating the Beers criteria for potentially inappropriate medication use in older adults: results of a US consensus panel of experts." Arch Intern Med 163 (2003): 2716-2724. [PMID: 14662625]
4 Forgue ST, Reece PA, Sedman AJ, Devries TM "Inhibition of tacrine oral clearance by cimetidine." Clin Pharmacol Ther 59 (1996): 444-9. [PMID: 8612390]
5 Product Information. Cognex (tacrine). Parke-Davis, Morris Plains, NJ.
6 Roe CM, Anderson MJ, Spivack B "Use of anticholinergic medications by older adults with dementia." J Am Geriatr Soc 50 (2002): 836-42. [PMID: 12028169]