Amiloride
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| Clinical data | |
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| Trade names | Midamor, others |
| AHFS/Drugs.com | Monograph |
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| Routes of administration |
by mouth |
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| Pharmacokinetic data | |
| Bioavailability | Readily absorbed, 15–25% |
| Protein binding | ~23% |
| Metabolism | Nil |
| Onset of action | 2 hours (peak at 6–10 hours, duration ~24 hours) |
| Biological half-life | 6 to 9 hours |
| Excretion | urine (20–50%), feces (40%) |
| Identifiers | |
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| Synonyms | MK-870 |
| CAS Number | |
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| ChEMBL | |
| ECHA InfoCard | 100.018.205 |
| Chemical and physical data | |
| Formula | C6H8ClN7O |
| Molar mass | 229.627 g/mol |
| 3D model (JSmol) | |
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Amiloride, sold under the trade name Midamor among others, is a medication typically used with other medications to treat high blood pressure or swelling due to heart failure or cirrhosis of the liver.[1][2] Amiloride is often used with a thiazide or loop diuretic.[2] It is taken by mouth.[1] Onset of action is about two hours and it lasts for about a day.[2]
Common side effects include high blood potassium, vomiting, loss of appetite, rash, and headache.[1] The risk of high blood potassium is greater in those with kidney problems, diabetes, and those who are older.[1] Amiloride is in the potassium-sparing diuretic family of medications.[1] It works by increasing the amount of sodium and decreasing the amount of potassium released by the distal tubule of the kidney.[2]
Amiloride was developed in 1967.[3] It is on the World Health Organization's List of Essential Medicines, the most effective and safe medicines needed in a health system.[4] In the United States the wholesale price of a month of medication is about 20.10 USD.[5] In the United Kingdom a month of medication costs the NHS about 24 pounds.[6]
Contents
Contraindications[edit]
Amiloride is contraindicated in people with Addison's disease, hyperkalaemia, hyponatremia and anuria.[7]
Adverse effects[edit]
- Common adverse effects:[7]
- Hyperkalemia
- Hyponatremia
- Dehydration
- Headache
- Polyuria
- Fatigue
- Nausea
- Vomiting
- Stomach pain
- Dizziness
- Anorexia
- Skin Rash
Structure[edit]
Amiloride's chemical structure contains a guanidinium group containing pyrazine derivative.
Mechanism of action[edit]
Amiloride works by directly blocking the epithelial sodium channel (ENaC) thereby inhibiting sodium reabsorption in the late distal convoluted tubules, connecting tubules, and collecting ducts in the nephron.[8] This promotes the loss of sodium and water from the body, but without depleting potassium. The drug is often used in conjunction with a thiazide diuretic to counteract the potassium-sparing effect. Due to its potassium-sparing capacities, hyperkalemia can occur. The risk of developing hyperkalemia is increased in patients who are also on ACE inhibitors, angiotensin II receptor antagonists, other potassium-sparing diuretics, or any potassium-containing supplements.
A fraction of the effects of amiloride is inhibition of cyclic GMP-gated cation channels in the inner medullary collecting duct.[9]
Amiloride has a second action on the heart, blocking Na+/H+ exchangers sodium–hydrogen antiporter 1 or NHE-1. This minimizes re-perfusion injury in ischemic attacks.
Amiloride also blocks the Na+/H+ antiporter on the apical surface of the proximal tubule cells, in the nephron, abolishing more than 80% of the action of angiotensin II on the secretion of hydrogen ions in proximal tubule cells.[10]
Amiloride was also tested as treatment of cystic fibrosis, but it was revealed inefficient in vivo due to its short time of action, therefore longer-acting epithelial sodium channel (ENaC) inhibitors may prove more effective, e.g. benzamil.[11]
Acid-sensing ion channels (ASICs) are also sensitive to inhibition by amiloride. ASICs are involved in nociceptor responses to pH.[12]
Society and culture[edit]
It is on the World Health Organization's List of Essential Medicines, the most important medications needed in a basic health system.[4]
Amiloride is listed on the world anti-doping agency's list of banned substances, it is considered a masking agent.[13]
Formulations and trade names[edit]
- Amiloride hydrochloride
- Midamor (U.S.)
- Co-amilozide (amiloride hydrochloride with hydrochlorothiazide)
- Co-amilofruse (amiloride hydrochloride with furosemide)
- Amiloride hydrochloride with cyclopenthiazide
- Amiloride hydrochloride with bumetanide
References[edit]
- ^ a b c d e "Amiloride Hydrochloride". The American Society of Health-System Pharmacists. Retrieved 8 December 2016.
- ^ a b c d WHO Model Formulary 2008 (PDF). World Health Organization. 2009. pp. 328, 330. ISBN 9789241547659. Retrieved 8 December 2016.
- ^ Progress in Drug Research/Fortschritte der Arzneimittelforschung/Progrés des recherches pharmaceutiques. Birkhäuser. 2013. p. 210. ISBN 9783034870948.
- ^ a b "WHO Model List of Essential Medicines (19th List)" (PDF). World Health Organization. April 2015. Retrieved 8 December 2016.
- ^ "NADAC as of 2016-12-07 | Data.Medicaid.gov". Centers for Medicare and Medicaid Services. Retrieved 28 December 2016.
- ^ British national formulary : BNF 69 (69 ed.). British Medical Association. 2015. p. 90. ISBN 9780857111562.
- ^ a b E-Facts and Comparisons: Amiloride Adverse effects 2016
- ^ Loffing, Johannes; Kaissling, Brigitte (2003). "Sodium and calcium transport pathways along the mammalian distal nephron: from rabbit to human". Am J Physiol Renal Physiol. 284 (4): F628–F643. PMID 12620920. doi:10.1152/ajprenal.00217.2002.
- ^ Walter F. Boron. Medical Physiology: A Cellular And Molecular Approaoch. Elsevier/Saunders. ISBN 1-4160-2328-3. page 875
- ^ M G Cogan, Angiotensin II: a powerful controller of sodium transport in the early proximal tubule, Hypertension. 1990;15:451-458, doi:10.1161/01.HYP.15.5.451, http://hyper.ahajournals.org/content/15/5/451
- ^ (Review)Pharmacological treatment of the biochemical defect in cystic fibrosis airways, H.C. Rodgers, A.J. Knoxhttp://erj.ersjournals.com/content/17/6/1314.full.pdf+html
- ^ Hunt and Koltzenburg 2005 'The neurobiology of pain'
- ^ "S5. Diuretics and masking agents - WADA". World Anti-Doping Agency. January 2016. Retrieved 1 September 2016.
