Loop Diuretics ( furosemide )

1. Thiazides (bendroflumethiazide) K Sparing Diuretics Amiloride Loop Diuretics (furosemide) Spironolactone

2. Loop diuretics e.g. Furosemide • Inhibits Cl- channel of the Na:K:Cl co-transporter(via competitive binding) • Therefore inhibits the whole transporter. • Increases ions in the lumen, makes the lumen hypertonic (therefore closer to the concentration of the medulla). • Stops water being absorbed into the medulla (decreases osmotic drag into the medulla). • Loop diuretics e.g. Furosemide • Inhibits Cl- channel of the Na:K:Cl co-transporter(via competitive binding) • Therefore inhibits the whole transporter. • Increases ions in the lumen, makes the lumen hypertonic (therefore closer to the concentration of the medulla) • Stops water being absorbed into the medulla • K sparing (both work in principle cells) • Amiloride: • Blocks ENaC channel • Therefore no gradient to made to let K out. • Increases Na conc in the collecting duct and takes water with it. • Spironolactone: • Competitively binds to aldosterone receptor and is an antagonist. • Aldosterone normally upregulates the number of ENaC channels at the lumen membrane. • Less ENaC channels = less Na being swapped for K (as above for amiloride) • Thiazides e.g. Bendroflumethiazide • Blocks the Na:CL transporter. • Increases ions in the lumen, causes water to move into the lumen. (increases osmotic drag into the lumen. • Note: if Na conc in tubule is high/normal and systemic Na is low renin will be secreted! This will counteract the effects  of loops and thiazides! Block ACE using ACE inhibitors Via ACE Via Renin Angiotensinogen Angiotensin 1 Angiotensin 2 Aldosterone Block angiotensin 2 receptor using ARBs