amiloride
1 min read
Updated 2026-03-15
Contents
amiloride
Direct ENaC blocker at the collecting duct. Faster onset (~2h) than spironolactone. Uniquely counteracts four loop-diuretic complications simultaneously: metabolic alkalosis, hypokalaemia, hypernatraemia, and hypomagnesaemia. No large RCTs in ADHF — expert opinion level.
mechanism
Directly blocks the epithelial sodium channel (ENaC) on the collecting duct luminal membrane — does not act via the mineralocorticoid receptor. Non-genomic → onset ~2h (vs. 24–48h for spironolactone). Weak diuretic alone (~2% filtered Na⁺).
dosing
- 5–20 mg PO daily (can split BID)
- Start 5 mg, titrate on K⁺
- Avoid if K⁺ > 5.0 or eGFR < 10
key points
- Counteracts loop-induced complications simultaneously:
| Loop problem | Amiloride effect |
|---|---|
| Metabolic alkalosis | ↓ H⁺ secretion → corrects |
| Hypokalaemia | ↓ K⁺ secretion |
| Hypernatraemia | ↓ Na⁺ reabsorption |
| Hypomagnesaemia | ↓ Mg²⁺ wasting |
- Specific treatment for Liddle syndrome (gain-of-function ENaC mutation)
- Treats lithium-induced nephrogenic DI — blocks lithium entry via ENaC
always amiloride, never triamterene
Triamterene causes nephrolithiasis (triamterene stones), interstitial nephritis, and AKI. When an ENaC blocker is needed, always choose amiloride.
adverse effects
- Hyperkalaemia — the main risk; additive with ACEi/ARB/MRA
- Mild GI upset
- Hyperchloraemic metabolic acidosis (mild)