Amiloride
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| Clinical data | |
|---|---|
| Trade names | Midamor |
| AHFS/Drugs.com | Monograph |
| Pregnancy category |
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| Routes of administration |
Oral |
| ATC code | C03DB01 (WHO) |
| Legal status | |
| Legal status | |
| 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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Systematic (IUPAC) name: 3,5-diamino-6-chloro-N-(diaminomethylene)pyrazine-2-carboxamide
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| CAS Number | 2016-88-8  |
| PubChem (CID) | 16231 |
| IUPHAR/BPS | 2421 |
| DrugBank | DB00594 |
| ChemSpider | 15403 |
| UNII | 7M458Q65S3 |
| KEGG | D07447 |
| ChEBI | CHEBI:2639 |
| ChEMBL | CHEMBL945 |
| Chemical and physical data | |
| Formula | C6H8ClN7O |
| Molar mass | 229.627 g/mol |
| 3D model (Jmol) | Interactive image |
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Amiloride, trade name Midamor, is a potassium-sparing diuretic first approved for use in 1967 (then known as MK-870). It is used most often in the management of hypertension and congestive heart failure.
Contents
Society and culture[edit]
It is on the World Health Organization's List of Essential Medicines, a list of the most important medication needed in a basic health system.[1]
Amiloride is listed on the world anti-doping agency's list of banned substances, it is considered a masking agent.[2]
Structure[edit]
Amiloride's chemical structure contains a guanidinium group containing pyrazine derivative.
Contraindications[edit]
Amiloride is contraindicated in patients with Addison's disease, hyperkalaemia, hyponatremia and anuria.[3]
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.[4] 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 is high in patients who are also on ACE inhibitors, Angiotensin II receptor antagonists, other potassium-sparing diuretics like spironolactone, or any potassium-containing supplements. Amiloride also carries the risk of developing an arrhythmia or acidosis due to increased potassium.
A fraction of the effects of amiloride is inhibition of cyclic GMP-gated cation channels in the inner medullary collecting duct.[5]
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.[6]
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.[7]
Acid-sensing ion channels (ASICs) are also sensitive to inhibition by amiloride. ASICs are involved in nociceptor responses to pH.[8]
Adverse Effects[edit]
- Common adverse effects:[9]
- Hyperkalemia
- Hyponatremia
- Dehydration
- Headache
- Polyuria
- Fatigue
- Nausea
- Vomiting
- Stomach pain
- Dizziness
- Anorexia
- Skin Rash
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]
- ^ "WHO Model List of EssentialMedicines" (PDF). World Health Organization. October 2013. Retrieved 22 April 2014.
- ^ "S5. Diuretics and masking agents - WADA". World Anti-Doping Agency. January 2016. Retrieved 1 September 2016.
- ^ 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. doi:10.1152/ajprenal.00217.2002. PMID 12620920.
- ^ 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'
- ^ E-Facts and Comparisons: Amiloride Adverse effects 2016
