Diuretics
&
↑
Potassium sparing diuretic
Loop diuretic Thiazide diuretic, PSD CA inhibitors Osmotic diuretics
Property i
Thiazides- Chlorothiazide, ( the Spironolactone (Aldactone), Acetazolamide Mannitol
Furosemide
parent of the group, not very lipid- Eplerenone
Examples Ethacrynic acrid
soluble - only thiazide available for dorzolamide, brinzolamide
Bumetanide Amiloride
parenteral administration. )
Torsemide
bendroflumethiazide, Triamterene (Dytac)
hydrochlorothiazide
&
Related drugs - chlorthalidone,
indapamide and metolazone
( share structural similarities with them and
probably act at the same site on the nephron ,
have a longer duration of action)
All except ethacrynic acid, are Thiazides are sulfonamides
sulphonamides
Site of thick ascending limb of the loop distal tubule and connecting segment aldosterone-sensitive proximal convoluted tubule part in the proximal
action in of Henle (and perhaps the early cortical principal cells in the cortical tubule
nephron collecting tubule) collecting tubule
Efficacy High efficacy Moderate efficacy Low efficacy Low efficacy Low efficacy
Mechanism of
e, wit
an -ja F eje ↑E
osmotically active
action.
! riy
M
use hi M
agent that is
W--- W hi filtered by the
e ↑
!-- glomerulus but not
↑
E reabsorbed
proximal tubule and
descending limb of
Henle’s loop are
freely permeable to
water
, Luminal
Blood
Loop Luminal Blood Blood Catalyzes the
Luminal
-
diuretic dehydration of H2CO3 to Filtered water retain
Thiazide
" CO2 at the luminal within tubules and
↳ .....
diuretic Aldosterone
membrane and excretion urine
. I
8 PS Diuretic
->
kt
rehydration of CO2 to
-
ecT Nat AR
H2CO3 in the cytoplasm.
ENAC Expresion ↑ Na-K ATPase
↑
expression
E
",,ist Nat
① ATP ATP
(92+
K+
migzt
*
Nat
kt
②
CI-
①
y
Loss of
pin
⑭
Selectively
Na,K,Cl
inhibit the
luminal
Na+/K+/2Cl ⑪
Block the Na+/Cl transporter (NCC).
2
⑱
aldosterone
increase in Mg2+ and Ca2+ inhibit NaCl reabsorption
excretion binds to aldosterone receptor
-
lower intracellular Na+
upregulate
⑱
enhances Na+/Ca2+ exchange in the
Ne ⑲
Hypomagnesemia No basolateral membrane ENAC Na/K/ATPase
hypocalcaemia Expression pump
Na comes into cell
In the PCT, thiazide-induced volume through ENaC
vitamin D–induced intestinal absorption
depletion leads to enhanced Na+ and
passive Ca2+ reabsorption.
parathyroid hormone–induced renal negative potential in urine
reabsorption of Ca2+
K comes into the cell and gets
secreted into urine through a K
channel
&
↑
Potassium sparing diuretic
Loop diuretic Thiazide diuretic, PSD CA inhibitors Osmotic diuretics
Property i
Thiazides- Chlorothiazide, ( the Spironolactone (Aldactone), Acetazolamide Mannitol
Furosemide
parent of the group, not very lipid- Eplerenone
Examples Ethacrynic acrid
soluble - only thiazide available for dorzolamide, brinzolamide
Bumetanide Amiloride
parenteral administration. )
Torsemide
bendroflumethiazide, Triamterene (Dytac)
hydrochlorothiazide
&
Related drugs - chlorthalidone,
indapamide and metolazone
( share structural similarities with them and
probably act at the same site on the nephron ,
have a longer duration of action)
All except ethacrynic acid, are Thiazides are sulfonamides
sulphonamides
Site of thick ascending limb of the loop distal tubule and connecting segment aldosterone-sensitive proximal convoluted tubule part in the proximal
action in of Henle (and perhaps the early cortical principal cells in the cortical tubule
nephron collecting tubule) collecting tubule
Efficacy High efficacy Moderate efficacy Low efficacy Low efficacy Low efficacy
Mechanism of
e, wit
an -ja F eje ↑E
osmotically active
action.
! riy
M
use hi M
agent that is
W--- W hi filtered by the
e ↑
!-- glomerulus but not
↑
E reabsorbed
proximal tubule and
descending limb of
Henle’s loop are
freely permeable to
water
, Luminal
Blood
Loop Luminal Blood Blood Catalyzes the
Luminal
-
diuretic dehydration of H2CO3 to Filtered water retain
Thiazide
" CO2 at the luminal within tubules and
↳ .....
diuretic Aldosterone
membrane and excretion urine
. I
8 PS Diuretic
->
kt
rehydration of CO2 to
-
ecT Nat AR
H2CO3 in the cytoplasm.
ENAC Expresion ↑ Na-K ATPase
↑
expression
E
",,ist Nat
① ATP ATP
(92+
K+
migzt
*
Nat
kt
②
CI-
①
y
Loss of
pin
⑭
Selectively
Na,K,Cl
inhibit the
luminal
Na+/K+/2Cl ⑪
Block the Na+/Cl transporter (NCC).
2
⑱
aldosterone
increase in Mg2+ and Ca2+ inhibit NaCl reabsorption
excretion binds to aldosterone receptor
-
lower intracellular Na+
upregulate
⑱
enhances Na+/Ca2+ exchange in the
Ne ⑲
Hypomagnesemia No basolateral membrane ENAC Na/K/ATPase
hypocalcaemia Expression pump
Na comes into cell
In the PCT, thiazide-induced volume through ENaC
vitamin D–induced intestinal absorption
depletion leads to enhanced Na+ and
passive Ca2+ reabsorption.
parathyroid hormone–induced renal negative potential in urine
reabsorption of Ca2+
K comes into the cell and gets
secreted into urine through a K
channel
