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Diuretics: Na+ channel inhibitors (general properties and chemical…
Diuretics: Na+ channel inhibitors
general properties and chemical structure
weak diuretics
K+ and H+ sparing diuretics
chemical structure
basic compounds with amino group that can be protonated
triamterene
activated by hydroxylation & sulfation
MOA
amiloride and triamterene, as organic cations, are secreted by the organic cation secretory mechanism into the proximal convoluted tubule
(OCT2 -> MATE)
they travel along the nephron to the collecting duct
They block Na+ channels in the apical membrane of the principal cells in the collecting duct
(these Na+ channel are called epithelial Na+ channels and they are different from the voltage-gated Na+ channels)
Effects
Primary
Na+ (and Cl-) reabsorption↓
weak diuretics (because only 2% of filtered Na+ and GFR is reabsorbed in the collecting duct)
Secondary
lumen-negative transepithelial potential difference↓ (by decreasing Na+ reabsorption)
K+ secretion↓ : through K+ channels in principal cells (K+ sparing effect)
H+ secretion↓ : through H+ ATPase (proton pump) in the intercalated cells (metabolic acidosis)
Pharmacokinetics
amiloride
oral bioavailability
Good
T1/2
6-9 hours
Elimination
Urinary excretion in unchanged form
Traimterene
Oral bioavailability
Moderate
Activation
largely by hydroxylation and sulfation
elimination
partly by renal excretion / largely by hydroxylation and sulfation
T1/2
1-2 hours (parent compound)
3 hours (sulfate ester)
Side effect
Hyperkalemia (due to K+ sparing effect)
Should not be combined with ACE inhibitors and aldosterone antagonists (may potentiate each other)
May be dangerous in patient with renal impairment (due to K+) retention
GI disturbance
Nausea
Vomiting
Diarrhea
Triamterene only
Megaloblastic anemia -> due to weak folic acid antagonist effect
Interstitial nephritis / crystalluria (4-OH-triamterene-sulfate is poorly water soluble)
Photosensitization (i.e. UV light converts it into all allergen)
Indications
diuretics (weak diuretics)
Na+ channel inhibitors they are often combined with thiazides or loop diuretics to decreasing their K+ losing effect
cystic fibrosis
aerosolized amiloride solution is given by inhalation
blocks Na+ channel in bronchial mucosa -> dilutes the bronchial secretion -> improves the mucociliary clearance
Li+ intoxication