Details of Drug Interaction | MecDDI

Drug General Information (ID: DDILKYZ4B6)
Drug Name			Eplerenone		Drug Info		Guanfacine		Drug Info
Drug Type		Small molecule				Small molecule
Therapeutic Class		Antihypertensive Agents				Antiadrenergic Agents
Structure

Mechanism of Eplerenone-Guanfacine Interaction (Severity Level: Moderate)
Additive hypotensive effects Click to Show/Hide Mechanism Graph

Drug Name		Eplerenone				Guanfacine
Mechanism		Antihypertensive agent Mineralocorticoid receptor Antagonist				Antihypertensive agent Alpha-2 adrenergic receptor Agonist
Key Mechanism Factor 1
		Factor Name		Mineralocorticoid receptor				× Structure Sequence METKGYHSLPEGLDMERRWGQVSQAVERSSLGPTERTDENNYMEIVNVSCVSGAIPNNSTQGSSKEKQELLPCLQQDNNRPGILTSDIKTELESKELSATVAESMGLYMDSVRDADYSYEQQNQQGSMSPAKIYQNVEQLVKFYKGNGHRPSTLSCVNTPLRSFMSDSGSSVNGGVMRAVVKSPIMCHEKSPSVCSPLNMTSSVCSPAGINSVSSTTASFGSFPVHSPITQGTPLTCSPNVENRGSRSHSPAHASNVGSPLSSPLSSMKSSISSPPSHCSVKSPVSSPNNVTLRSSVSSPANINNSRCSVSSPSNTNNRSTLSSPAASTVGSICSPVNNAFSYTASGTSAGSSTLRDVVPSPDTQEKGAQEVPFPKTEEVESAISNGVTGQLNIVQYIKPEPDGAFSSSCLGGNSKINSDSSFSVPIKQESTKHSCSGTSFKGNPTVNPFPFMDGSYFSFMDDKDYYSLSGILGPPVPGFDGNCEGSGFPVGIKQEPDDGSYYPEASIPSSAIVGVNSGGQSFHYRIGAQGTISLSRSARDQSFQHLSSFPPVNTLVESWKSHGDLSSRRSDGYPVLEYIPENVSSSTLRSVSTGSSRPSKICLVCGDEASGCHYGVVTCGSCKVFFKRAVEGQHNYLCAGRNDCIIDKIRRKNCPACRLQKCLQAGMNLGARKSKKLGKLKGIHEEQPQQQQPPPPPPPPQSPEEGTTYIAPAKEPSVNTALVPQLSTISRALTPSPVMVLENIEPEIVYAGYDSSKPDTAENLLSTLNRLAGKQMIQVVKWAKVLPGFKNLPLEDQITLIQYSWMCLSSFALSWRSYKHTNSQFLYFAPDLVFNEEKMHQSAMYELCQGMHQISLQFVRLQLTFEEYTIMKVLLLLSTIPKDGLKSQAAFEEMRTNYIKELRKMVTKCPNNSGQSWQRFYQLTKLLDSMHDLVSDLLEFCFYTFRESHALKVEFPAMLVEIISDQLPKVESGNAKPLYFHRK
		Gene Name		NR3C2
		Uniprot ID		MCR_HUMAN
		KEGG Pathway		hsa:4306
		Protein Family		Nuclear hormone receptor family
		Protein Function		Receptor for both mineralocorticoids (MC) such as aldosterone and glucocorticoids (GC) such as corticosterone or cortisol. Binds to mineralocorticoid response elements (MRE) and transactivates target genes. The effect of MC is to increase ion and water transport and thus raise extracellular fluid volume and blood pressure and lower potassium levels. Click to Show/Hide
Key Mechanism Factor 2
		Factor Name		Adrenergic receptor alpha-2				Structure Sequence
		Protein Family		G-protein coupled receptor 1 family
		Protein Function		Alpha-2 adrenergic receptors mediate the catecholamine-induced inhibition of adenylate cyclase through the action of G proteins. The rank order of potency for agonists of this receptor is oxymetazoline > clonidine > epinephrine > norepinephrine > phenylephrine > dopamine > p-synephrine > p-tyramine > serotonin = p-octopamine. For antagonists, the rank order is yohimbine > phentolamine = mianserine > chlorpromazine = spiperone = prazosin > propanolol > alprenolol = pindolol. Click to Show/Hide
Mechanism Description		Additive hypotensive effects by the combination of Eplerenone and Guanfacine

Recommended Action
Management		Caution is advised during coadministration of these agents. Dosage adjustments may be required and hemodynamic responses should be monitored during concomitant therapy. Patients should be advised to avoid rising abruptly from a sitting or recumbent position and to notify their doctor if they experience dizziness, lightheadedness, syncope, orthostasis, or tachycardia. Patients should also avoid driving or operating hazardous machinery until they know how the medications affect them.

References
1	Cerner Multum, Inc. "Australian Product Information.".
2	Cerner Multum, Inc. "UK Summary of Product Characteristics.".
3	Product Information. Tenex (guanfacine). Wyeth-Ayerst Laboratories, Philadelphia, PA.