Details of Drug Interaction

Details of Drug-Drug Interaction

 Drug General Information (ID: DDIMRXC79W)
  Drug Name Trandolapril Drug Info Metolazone Drug Info
  Drug Type Small molecule Small molecule
  Therapeutic Class Antihypertensive Agents Antihypertensive Agents
  Structure

 Mechanism of Trandolapril-Metolazone Interaction (Severity Level: Moderate)
     Additive hypotensive effects Click to Show/Hide Mechanism Graph
Could Not Find 2D Structure
      Drug Name Trandolapril Metolazone
      Mechanism Antihypertensive agent
Angiotensin-converting enzyme  Inhibitor 		Hypotensive effects
Solute carrier family 12 member 3  Blocker
      Key Mechanism Factor 1
Factor Name Angiotensin-converting enzyme
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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 Solute carrier family 12 member 3
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Structure Sequence
MAELPTTETPGDATLCSGRFTISTLLSSDEPSPPAAYDSSHPSHLTHSSTFCMRTFGYNTIDVVPTYEHYANSTQPGEPRKVRPTLADLHSFLKQEGRHLHALAFDSRPSHEMTDGLVEGEAGTSSEKNPEEPVRFGWVKGVMIRCMLNIWGVILYLRLPWITAQAGIVLTWIIILLSVTVTSITGLSISAISTNGKVKSGGTYFLISRSLGPELGGSIGLIFAFANAVGVAMHTVGFAETVRDLLQEYGAPIVDPINDIRIIAVVSVTVLLAISLAGMEWESKAQVLFFLVIMVSFANYLVGTLIPPSEDKASKGFFSYRADIFVQNLVPDWRGPDGTFFGMFSIFFPSATGILAGANISGDLKDPAIAIPKGTLMAIFWTTISYLAISATIGSCVVRDASGVLNDTVTPGWGACEGLACSYGWNFTECTQQHSCHYGLINYYQTMSMVSGFAPLITAGIFGATLSSALACLVSAAKVFQCLCEDQLYPLIGFFGKGYGKNKEPVRGYLLAYAIAVAFIIIAELNTIAPIISNFFLCSYALINFSCFHASITNSPGWRPSFQYYNKWAALFGAIISVVIMFLLTWWAALIAIGVVLFLLLYVIYKKPEVNWGSSVQAGSYNLALSYSVGLNEVEDHIKNYRPQCLVLTGPPNFRPALVDFVGTFTRNLSLMICGHVLIGPHKQRMPELQLIANGHTKWLNKRKIKAFYSDVIAEDLRRGVQILMQAAGLGRMKPNILVVGFKKNWQSAHPATVEDYIGILHDAFDFNYGVCVMRMREGLNVSKMMQAHINPVFDPAEDGKEASARVDPKALVKEEQATTIFQSEQGKKTIDIYWLFDDGGLTLLIPYLLGRKRRWSKCKIRVFVGGQINRMDQERKAIISLLSKFRLGFHEVHILPDINQNPRAEHTKRFEDMIAPFRLNDGFKDEATVNEMRRDCPWKISDEEITKNRVKSLRQVRLNEIVLDYSRDAALIVITLPIGRKGKCPSSLYMAWLETLSQDLRPPVILIRGNQENVLTFYCQ
Gene Name SLC12A3
Uniprot ID S12A3_HUMAN
KEGG Pathway hsa:6559
Protein Family SLC12A transporter family
Protein Function
Electroneutral sodium and chloride ion cotransporter. In kidney distal convoluted tubules, key mediator of sodium and chloride reabsorption (PubMed:21613606, PubMed:22009145). Receptor for the pro-inflammatory cytokine IL18. Contributes to IL18-induced cytokine production, including IFNG, IL6, IL18 and CCL2. May act either independently of IL18R1, or in a complex with IL18R1 (By similarity).
    Click to Show/Hide
      Mechanism Description
  • Additive hypotensive effects by the combination of Trandolapril and Metolazone 

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 Burnakis TG, Mioduch HJ "Combined therapy with captopril and potassium supplementation: a potential for hyperkalemia." Arch Intern Med 144 (1984): 2371-2. [PMID: 6391404]
2 Cerner Multum, Inc. "Australian Product Information.".
3 Champ JD "Case report: azotemia secondary to enalapril and diuretic use and the diagnosis of renovascular hypertension." Am J Med Sci 305 (1993): 25-7. [PMID: 8416678]
4 DeQuattro V "Comparison of benazepril and other antihypertensive agents alone and in combination with the diuretic hydrochlorothiazide." Clin Cardiol 14 (1991): iv28-32. [PMID: 1893639]
5 Fujimura A, Shimokawa Y, Ebihara A "Influence of captopril on urinary excretion of furosemide in hypertensive subjects." J Clin Pharmacol 30 (1990): 538-42. [PMID: 2191978]
6 Funck-Brentano C, Chatellier G, Alexandre JM "Reversible renal failure after combined treatment with enalapril and furosemide in a patient with congestive heart failure." Br Heart J 55 (1986): 596-8. [PMID: 3013264]
7 Good JM, Brady AJ, Noormohamed FH, Oakley CM, Cleland JG "Effect of intense angiotensin II suppression on the diuretic response to furosemide during chronic ACE inhibition." Circulation 90 (1994): 220-4. [PMID: 8026000]
8 Hume AL, Murphy JL, Lauerman SE "Angiotensin-converting enzyme inhibitor-induced cough." Pharmacotherapy 9 (1989): 88-90. [PMID: 2542908]
9 Lederle RM "Captopril and hydrochlorothiazide in the fixed combination multicenter trial." J Cardiovasc Pharmacol 7 (1985): S63-9. [PMID: 2580179]
10 Lee HB, Blaufox MD "Renal functional response to captopril during diuretic therapy." J Nucl Med 33 (1992): 739-43. [PMID: 1569484]
11 McLay JS, McMurray JJ, Bridges AB, Fraser CG, Struthers AD "Acute effects of captopril on the renal actions of furosemide in patients with chronic heart failure." Am Heart J 126 (1993): 879-86. [PMID: 8213445]
12 Motwani JG, Fenwick MK, Morton JJ, Struthers AD "Furosemide-induced natriuresis is augmented by ultra-low-dose captopril but not by standard doses of captopril in chronic heart failure." Circulation 86 (1992): 439-45. [PMID: 1638713]
13 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]
14 Product Information. Aceon (perindopril). Solvay Pharmaceuticals Inc, Marietta, GA.
15 Product Information. Capoten (captopril). Bristol-Myers Squibb, Princeton, NJ.
16 Product Information. Lexxel (enalapril-felodipine). Astra Pharmaceuticals, Wayne, PA.
17 Product Information. Vasotec (enalapril). Merck & Co, Inc, West Point, PA.
18 Product Information. Zestrel (lisinopril) Astra-Zeneca Pharmaceuticals, Wilmington, DE.
19 Radley AS, Fitzpatrick RW "An evaluation of the potential interaction between enalapril and amiloride." J Clin Pharm Ther 12 (1987): 319-23. [PMID: 2824540]
20 Reader C, Peyregne EA, Suarez LD "Amrinone therapy in congestive cardiomyopathy." Am Heart J 105 (1983): 1045. [PMID: 6858829]
21 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]
22 Thind GS "Renal insufficiency during angiotensin-converting enzyme inhibitor therapy in hypertensive patients with no renal artery stenosis." J Clin Hypertens 1 (1985): 337-43. [PMID: 3014079]
23 Weisser K, Schloos J, Jakob S, et al "The influence of hydrochlorothiazide on the pharmacokinetics of enalapril in elderly patients." Eur J Clin Pharmacol 43 (1992): 173-7. [PMID: 1330574]