Details of Drug Interaction | MecDDI

Drug General Information (ID: DDIDS45AFV)
Drug Name			Isosorbide mononitrate		Drug Info		Quetiapine		Drug Info
Drug Type		Small molecule				Small molecule
Therapeutic Class		Vasodilator Agents				Antipsychotic Agents
Structure

Mechanism of Isosorbide mononitrate-Quetiapine Interaction (Severity Level: Moderate)
Additive hypotensive effects Click to Show/Hide Mechanism Graph

Drug Name		Isosorbide mononitrate				Quetiapine
Mechanism		Hypotensive effects Guanylate cyclase Agonist				Hypotensive effects Dopamine D2 receptor Agonist
Key Mechanism Factor 1
		Factor Name		Guanylate cyclase soluble				Structure Sequence
		Protein Family		Adenylyl cyclase class-4/guanylyl cyclase family
		Protein Function		There are two types of guanylate cyclases: soluble forms and membrane-associated receptor forms. Activated by nitric oxide in the presence of magnesium or manganese ions. Click to Show/Hide
Key Mechanism Factor 2
		Factor Name		Dopamine D2 receptor				× Structure Sequence MDPLNLSWYDDDLERQNWSRPFNGSDGKADRPHYNYYATLLTLLIAVIVFGNVLVCMAVSREKALQTTTNYLIVSLAVADLLVATLVMPWVVYLEVVGEWKFSRIHCDIFVTLDVMMCTASILNLCAISIDRYTAVAMPMLYNTRYSSKRRVTVMISIVWVLSFTISCPLLFGLNNADQNECIIANPAFVVYSSIVSFYVPFIVTLLVYIKIYIVLRRRRKRVNTKRSSRAFRAHLRAPLKGNCTHPEDMKLCTVIMKSNGSFPVNRRRVEAARRAQELEMEMLSSTSPPERTRYSPIPPSHHQLTLPDPSHHGLHSTPDSPAKPEKNGHAKDHPKIAKIFEIQTMPNGKTRTSLKTMSRRKLSQQKEKKATQMLAIVLGVFIICWLPFFITHILNIHCDCNIPPVLYSAFTWLGYVNSAVNPIIYTTFNIEFRKAFLKILHC
		Gene Name		DRD2
		Uniprot ID		DRD2_HUMAN
		KEGG Pathway		hsa:1813
		Protein Family		G-protein coupled receptor 1 family
		Protein Function		Dopamine receptor whose activity is mediated by G proteins which inhibit adenylyl cyclase (PubMed:21645528). Positively regulates postnatal regression of retinal hyaloid vessels via suppression of VEGFR2/KDR activity, downstream of OPN5 (By similarity). Click to Show/Hide
Mechanism Description		Additive hypotensive effects by the combination of Isosorbide mononitrate and Quetiapine

Recommended Action
Management		Close clinical monitoring for development of hypotension is recommended if phenothiazines or neuroleptic agents are used in patients receiving antihypertensive medications or vasodilators. A lower starting dosage and slower titration of the phenothiazine or neuroleptic may be appropriate, especially in the elderly. Patients should be advised to avoid rising abruptly from a sitting or recumbent position and to notify their physician if they experience dizziness, lightheadedness, syncope, orthostasis, or tachycardia. Patients should also avoid driving or operating hazardous machinery.

References
1	Aronowitz JS, Chakos MH, Safferman AZ, Lieberman JA "Syncope associated with the combination of clozapine and enalapril." J Clin Psychopharmacol 14 (1994): 429-30. [PMID: 7884028]
2	Fruncillo R, Gibbons W, Vlasses P, Ferguson R "Severe hypotension associated with concurrent clonidine and antipsychotic medication." Am J Psychiatry 142 (1985): 274. [PMID: 2857531]
3	Markowitz JS, Wells BG, Carson WH "Interactions between antipsychotic and antihypertensive drugs." Ann Pharmacother 29 (1995): 603-9. [PMID: 7663034]
4	Product Information. Abilify (aripiprazole). Bristol-Myers Squibb, Princeton, NJ.
5	Product Information. Clozaril (clozapine). Novartis Pharmaceuticals, East Hanover, NJ.
6	Product Information. Geodon (ziprasidone). Pfizer US Pharmaceuticals, New York, NY.
7	Product Information. Rexulti (brexpiprazole). Otsuka American Pharmaceuticals Inc, Rockville, MD.
8	Product Information. Risperdal (risperidone). Janssen Pharmaceutica, Titusville, NJ.
9	Product Information. Seroquel (quetiapine). Zeneca Pharmaceuticals, Wilmington, DE.
10	Product Information. Zyprexa (olanzapine). Lilly, Eli and Company, Indianapolis, IN.
11	White WB "Hypotension with postural syncope secondary to the combination of chlorpromazine and captopril." Arch Intern Med 146 (1986): 1833-4. [PMID: 3530167]