Details of Drug Interaction | MecDDI

Drug General Information (ID: DDIKGZBX3L)
Drug Name			Physostigmine		Drug Info		Doxepin (topical)		Drug Info
Drug Type		Small molecule				Small molecule
Therapeutic Class		Ophthalmic Glaucoma Agents/Antidotes				Antidepressants
Structure

Mechanism of Physostigmine-Doxepin (topical) Interaction (Severity Level: Moderate)
Antagonize the effect of cholinergic agents Click to Show/Hide Mechanism Graph

Drug Name		Physostigmine				Doxepin (topical)
Mechanism		Cholinergic effects Acetylcholinesterase Inhibitor				Anticholinergic effects Muscarinic acetylcholine receptor Antagonist
Key Mechanism Factor 1
		Factor Name		Acetylcholinesterase				× 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. Click to Show/Hide
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. Click to Show/Hide
Mechanism Description		Antagonize the effect of Physostigmine when combined with Doxepin (topical)

Recommended Action
Management		Drugs that possess anticholinergic activity should generally be avoided in patients with Alzheimer's disease or other cognitive impairment, regardless of whether they are receiving an acetylcholinesterase inhibitor. For patients requiring treatment to counteract adverse effects of acetylcholinesterase inhibitor therapy (e.g., gastrointestinal intolerance, urinary problems), an agent without anticholinergic properties should be used whenever possible. Otherwise, a dosage reduction, slower titration, or even discontinuation of the acetylcholinesterase inhibitor should be considered. For patients who are already receiving an acetylcholinesterase inhibitor with anticholinergic agents, every attempt should be made to discontinue the latter or substitute them with less anticholinergic alternatives.

References
1	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]
2	Edwards KR, O'Connor JT "Risk of delirium with concomitant use of tolterodine and acetylcholinesterase inhibitors." J Am Geriatr Soc 50 (2002): 1165-6. [PMID: 12110086]
3	Katz IR, Sands LP, Bilker W, DiFilippo S, Boyce A, D'Angelo K "Identification of medications that cause cognitive impairment in older people: the case of oxybutynin chloride." J Am Geriatr Soc 46 (1998): 8-13. [PMID: 9434659]