Cimetidine Amiloride

Clinically important, potentially hazardous interactions with allopurinol, amiloride, cimetidine, corticosteroids, cyclosporine, insulin, lithium, potassium sparing diuretics, potassium supplements, procainamide, spironolactone, triamterene... 

The first inhibitor of NHE, amiloride, was identified in 1982. This drug is a potassium-sparing diuretic that also inhibits the sodium-calcium exchanger and the conductive Na+ channel. Not all the NHE isoforms are inhibited equally by amiloride NHE1 and 2 are responsive, NHE5 is partially responsive and NHE3, 4 and 7 are resistant. Other weak and non-specific inhibitors are clonidine and cimetidine. 

There is a risk of acute renal failure when iodi-nated contrast material that is used for radiological studies is administered with metformin. Metformin therapy is stopped for 48 hours before and after radiological studies using iodinated material. Alcohol, amiloride, digoxin, morphine, procainamide, quini-dine, quinine ranitidine, triamterene, trimethoprim, vancomycin, cimetidine, and furosemide all increase the risk of hypoglycemia. There is an increased risk of lactic acidosis when metformin is administered with the glucocorticoids. 

Na oi and was partially blocked by amiloride but not by cimetidine. Since these investigators also found that amiloride and cimetidine bound competitively with Na" at the external transport site of the placental brush border Na /H exchanger, they concluded that the vicinal dithiol groups are necessary for transport function but are located at a site distinct from the external transport site. 

T Pancreatic insulin release Metformin Peripheral insulin sensitivity hepatic glucose output/production i intestinal glucose absorption Dose Ist-line (naive pts), 1.25/250 mg PO daily-bid 2nd-line, 2.5/500 mg or 5/500 mg bid (max 20/2000 mg) take w/ meals, slowly T dose hold before 48 h after ionic contrast media Caution [C, -] Contra SCr >1.4 mg/dL in females or >1.5 mg/dL in males hypoxemic conditions (sepsis, recent MI) alcoholism metabolic acidosis liver Dz Disp Tabs SE HA, hypoglycemia, lactic acidosis, anorexia, N/V, rash Additional Interactions T Effects W/ amiloride, ciprofloxacin cimetidine, digoxin, miconazole, morphine, nifedipine, procainamide, quinidine, quinine, ranitidine, triamterene,... 

Gastrointestinal system Carbenoxolone Cimetidine Amiloride, spironolactone Antacids Inhibition of ulcer healing. Reduced absorption if taken simultaneously. 

Drugs that can precipitate lactic acidosis in patients taking metformin include ACE inhibitors, thiazide diuretics, NSAIDs, and drugs such as furosemide, nifedipine, cimetidine, amiloride, triamterene, trimethoprim, and digoxin, which are all secreted in the renal tubules, compete with metformin, and can contribute to increased plasma metformin concentrations (76). 

Figure 6.3 Plot of the fraction of dose absorbed (in %) of various drugs as a function of the permeability estimates in the Caco-2 system. Key 1 D-glucose 2 verapamil 3 piroxicam 4 phenylalanine 5 cyclosporin 6 enalapril 7 cephalexim 8 losartan 9 lisinopril 10 amoxicillin 11 methyldopa 12 naproxen 13 an-tipyrine 14 desipramine 15 propanolol 16 amiloride 17 metoprolol 18 terbu-taline 19 mannitol 20 cimetidine 21 ranitidine 22 enalaprilate 23 atenolol 24 hydrochlorothiazide.

Transporter absorptive effects predominant Examples. Acyclovir, Amiloride -, Amoxicillin Atenolol Atropine, Bidisomide Bisphosphonates Captoprit, Cefazolin Cetirizine Cimetidine Ciprofloxacin, Cloxacillin Dicloxacillin Erythromycin - -, Famotidine Fexofenadine Folinic acid Furosemide, Ganciclovir Hydrochlorothiazide, Lisinopril Metformin Methotrexate, Nadolol Penicillins Pravastatin Ranitidine Tetracycline Trimethoprim Valsartan Zalcitabine... 

Noninterfering acetaminophen, amiloride, aspirin, atenolol, chlorothiazide, cimetidine, cyclopenthiazide, diazepam, furosemide, indapamide, labetalol, lorazepam, metoprolol, phenytoin, propranolol, ranitidine, salicylic acid, theophylline... 

Noninterfering amiloride, acebutolol, acenocoumarol, acetaminophen, aspirin, allopuri-nol, ambroxol, amoxicillin, atenolol, bendroflumethiazide, benzbromarone, bezafibrate, biperiden, bisacodyl, bromazepam, butizide, captopril, cimetidine, ciprofloxacin, clobu-tinol, clonidine, cotinine, diazepam, diclofenac, digitoxin, digoxin, dihydrocodeine, dihy-droergotamine, diltiazem, doxepin, doxycycline, enalapril, erythromycin, fenoterol, furosemide, glibenclamide, heparin, h3qjoxanthine, ibuprofen, indomethacin, isosorbide... 

A study in 8 healthy subjects given amiloride 5 mg daily found that cime-tidine 400 mg twice daily for 12 days reduced the renal elearance of amiloride by 17% and reduced its urinary excretion from 65% to 53%. Amiloride also reduced the excretion of cimetidine from 43% to 32%, and the AUC was reduced by 14%. No changes in the diuretie effects (urinary volume, sodium or potassium excretion) occurred. It seems that each drug reduces the gastrointestinal absorption of the other drug by as yet unidentified mechanisms. The overall plasma levels of the amiloride remain unchanged because the reduced absorption is offset by a reduction in its renal excretion. These mutual interactions do not seem to be clinically significant. 

Somogyi AA, Hovens CM, Muirhead MR, Bochner F, Renal tubular secretion of amiloride and its inhibition by cimetidine in humans and in an animal model. DrugMetab Dispos (1989) 17, 190-6,... 

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