Details of Drug Interaction | MecDDI

Drug General Information (ID: DDI50ITV9C)
Drug Name			Moexipril		Drug Info		Diclofenamide		Drug Info
Drug Type		Small molecule				Small molecule
Therapeutic Class		Antihypertensive Agents				Ophthalmic Glaucoma Agents
Structure

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

Drug Name		Moexipril				Diclofenamide
Mechanism		Antihypertensive agent Angiotensin-converting enzyme Inhibitor				Hypotensive effects Carbonic anhydrase II Inhibitor
Key Mechanism Factor 1
		Factor Name		Angiotensin-converting enzyme				× Structure Sequence MGAASGRRGPGLLLPLPLLLLLPPQPALALDPGLQPGNFSADEAGAQLFAQSYNSSAEQVLFQSVAASWAHDTNITAENARRQEEAALLSQEFAEAWGQKAKELYEPIWQNFTDPQLRRIIGAVRTLGSANLPLAKRQQYNALLSNMSRIYSTAKVCLPNKTATCWSLDPDLTNILASSRSYAMLLFAWEGWHNAAGIPLKPLYEDFTALSNEAYKQDGFTDTGAYWRSWYNSPTFEDDLEHLYQQLEPLYLNLHAFVRRALHRRYGDRYINLRGPIPAHLLGDMWAQSWENIYDMVVPFPDKPNLDVTSTMLQQGWNATHMFRVAEEFFTSLELSPMPPEFWEGSMLEKPADGREVVCHASAWDFYNRKDFRIKQCTRVTMDQLSTVHHEMGHIQYYLQYKDLPVSLRRGANPGFHEAIGDVLALSVSTPEHLHKIGLLDRVTNDTESDINYLLKMALEKIAFLPFGYLVDQWRWGVFSGRTPPSRYNFDWWYLRTKYQGICPPVTRNETHFDAGAKFHVPNVTPYIRYFVSFVLQFQFHEALCKEAGYEGPLHQCDIYRSTKAGAKLRKVLQAGSSRPWQEVLKDMVGLDALDAQPLLKYFQPVTQWLQEQNQQNGEVLGWPEYQWHPPLPDNYPEGIDLVTDEAEASKFVEEYDRTSQVVWNEYAEANWNYNTNITTETSKILLQKNMQIANHTLKYGTQARKFDVNQLQNTTIKRIIKKVQDLERAALPAQELEEYNKILLDMETTYSVATVCHPNGSCLQLEPDLTNVMATSRKYEDLLWAWEGWRDKAGRAILQFYPKYVELINQAARLNGYVDAGDSWRSMYETPSLEQDLERLFQELQPLYLNLHAYVRRALHRHYGAQHINLEGPIPAHLLGNMWAQTWSNIYDLVVPFPSAPSMDTTEAMLKQGWTPRRMFKEADDFFTSLGLLPVPPEFWNKSMLEKPTDGREVVCHASAWDFYNGKDFRIKQCTTVNLEDLVVAHHEMGHIQYFMQYKDLPVALREGANPGFHEAIGDVLALSVSTPKHLHSLNLLSSEGGSDEHDINFLMKMALDKIAFIPFSYLVDQWRWRVFDGSITKENYNQEWWSLRLKYQGLCPPVPRTQGDFDPGAKFHIPSSVPYIRYFVSFIIQFQFHEALCQAAGHTGPLHKCDIYQSKEAGQRLATAMKLGFSRPWPEAMQLITGQPNMSASAMLSYFKPLLDWLRTENELHGEKLGWPQYNWTPNSARSEGPLPDSGRVSFLGLDLDAQQARVGQWLLLFLGIALLVATLGLSQRLFSIRHRSLHRHSHGPQFGSEVELRHS
		Gene Name		ACE
		Uniprot ID		ACE_HUMAN
		KEGG Pathway		hsa:1636
		Protein Family		Peptidase M2 family
		Protein Function		Converts angiotensin I to angiotensin II by release of the terminal His-Leu, this results in an increase of the vasoconstrictor activity of angiotensin. Also able to inactivate bradykinin, a potent vasodilator. Has also a glycosidase activity which releases GPI-anchored proteins from the membrane by cleaving the mannose linkage in the GPI moiety. Click to Show/Hide
Key Mechanism Factor 2
		Factor Name		Carbonic anhydrase II				× Structure Sequence MSHHWGYGKHNGPEHWHKDFPIAKGERQSPVDIDTHTAKYDPSLKPLSVSYDQATSLRILNNGHAFNVEFDDSQDKAVLKGGPLDGTYRLIQFHFHWGSLDGQGSEHTVDKKKYAAELHLVHWNTKYGDFGKAVQQPDGLAVLGIFLKVGSAKPGLQKVVDVLDSIKTKGKSADFTNFDPRGLLPESLDYWTYPGSLTTPPLLECVTWIVLKEPISVSSEQVLKFRKLNFNGEGEPEELMVDNWRPAQPLKNRQIKASFK
		Gene Name		CA2
		Uniprot ID		CAH2_HUMAN
		KEGG Pathway		hsa:760
		Protein Family		Alpha-carbonic anhydrase family
		Protein Function		Catalyzes the reversible hydration of carbon dioxide (PubMed:1909891, PubMed:1910042, PubMed:1336460, PubMed:8485129, PubMed:8399159, PubMed:8218160, PubMed:8262987, PubMed:8451242, PubMed:7901850, PubMed:7761440, PubMed:8639494, PubMed:9265618, PubMed:17330962, PubMed:9398308, PubMed:11327835, PubMed:12056894, PubMed:17346964, PubMed:12171926, PubMed:15453828, PubMed:16214338, PubMed:15865431, PubMed:16106378, PubMed:15300855, PubMed:15667203, PubMed:18942852, PubMed:11831900, PubMed:17251017). Can also hydrate cyanamide to urea (PubMed:10550681, PubMed:11015219). Stimulates the chloride-bicarbonate exchange activity of SLC26A6 (PubMed:15990874). Essential for bone resorption and osteoclast differentiation (PubMed:15300855). Involved in the regulation of fluid secretion into the anterior chamber of the eye. Contributes to intracellular pH regulation in the duodenal upper villous epithelium during proton-coupled peptide absorption. Click to Show/Hide
Mechanism Description		Additive hypotensive effects by the combination of Moexipril and Diclofenamide

Recommended Action
Management		Monitoring of blood pressure, diuresis, electrolytes, and renal function is recommended during coadministration. The possibility of first-dose hypotensive effects may be minimized by initiating therapy with small doses of the ACE inhibitor, or either discontinuing the diuretic temporarily or increasing the salt intake approximately one week prior to initiating an ACE inhibitor. alternatively, the patient may remain under medical supervision for at least two hours after the first dose of the ACE inhibitor, or until blood pressure has stabilized.

References
1	Murphy BF, Whitworth JA, Kincaid-Smith P "Renal insufficiency with combinations of angiotensin converting enzyme inhibitors and diuretics." Br Med J 288 (1984): 844-5. [PMID: 6322905]
2	Product Information. Lexxel (enalapril-felodipine). Astra Pharmaceuticals, Wayne, PA.
3	Sudoh T, Fujimura A, Shiga T, et al. "Influence of lisinopril on urinary electrolytes excretion after furosemide in healthy subjects." J Clin Pharmacol 33 (1993): 640-3. [PMID: 8396158]