Amiloride

Amiloride
Clinical data
Trade names Midamor
AHFS/Drugs.com Monograph
Pregnancy
category
  • US: B (No risk in non-human studies)
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
CAS Number 2016-88-8 YesY
PubChem (CID) 16231
IUPHAR/BPS 2421
DrugBank DB00594 YesY
ChemSpider 15403 YesY
UNII 7M458Q65S3 YesY
KEGG D07447 YesY
ChEBI CHEBI:2639 YesY
ChEMBL CHEMBL945 YesY
Chemical and physical data
Formula C6H8ClN7O
Molar mass 229.627 g/mol
3D model (Jmol) Interactive image
  (verify)

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.

Society and culture

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

Amiloride's chemical structure contains a guanidinium group containing pyrazine derivative.

Contraindications

Amiloride is contraindicated in patients with Addison's disease, hyperkalaemia, hyponatremia and anuria.[3]

Mechanism of action

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

Formulations and trade names

References

  1. ↑ "WHO Model List of EssentialMedicines" (PDF). World Health Organization. October 2013. Retrieved 22 April 2014.
  2. ↑ "S5. Diuretics and masking agents - WADA". World Anti-Doping Agency. January 2016. Retrieved 1 September 2016.
  3. ↑ E-Facts and Comparisons: Amiloride Adverse effects 2016
  4. ↑ 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.
  5. ↑ Walter F. Boron. Medical Physiology: A Cellular And Molecular Approaoch. Elsevier/Saunders. ISBN 1-4160-2328-3. page 875
  6. ↑ 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
  7. ↑ (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
  8. ↑ Hunt and Koltzenburg 2005 'The neurobiology of pain'
  9. ↑ E-Facts and Comparisons: Amiloride Adverse effects 2016
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