Irelia: The Blade Dancer; Jicama
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DIURETICS
Pharmacology (Lecture)
Dr. Ma. Luisa Crisostomo | March 12, 2021 | Topic 2
INTRODUCTION
Ø Natriuretic agents: increase renal sodium excretion
Ø Aquaretic agents: increase excretion of solute free
water
Ø Diuretic agents: block specific transport functions of
the renal tubules à increase urine volume
RENAL TRANSPORT SYSTEM
NEPHRON
Ø Structural and functional unit of the kidney
Ø Made up of tuft of capillaries called glomerulus
connected to tubes (PCT, DCT, loop of Henle,
collecting tubules)
Ø Responsible for urine formation
1) Glomerular filtration: water and solutes smaller
than proteins are forced through the capillary
walls and force of the glomerular capsule into the
renal tubule
2) Tubular reabsorption: water, glucose, amino
acids and ions are transported out of the filtrate
into the tubular cells and enter the capillary blood
3) Tubular secretion: substances not needed (i.e
drugs, creatinine) the body are removed in the
peritubular blood and secreted into the filter
PROXIMAL CONVOLUTED TUBULE
Ø Reabsorbs
1) Sodium (66%): via the sodium-potassium
ATPase
2) Sodium bicarbonate (NaHCO3;85%): via the
carbonic anhydrase activity
3) Potassium (65%): paracellular pathway
4) Glucose, amino acid (100%) and water (60%):
reabsorbed passively, maintaining osmolality in
nearly constant level
Ø Water permeability of the PCT is very high to
maintain the osmolality of proximal fluid at nearly
constant level, and the gradient from the tubule
lumen to the surrounding interstitium is very small.
DIURETICS THAT ACTS ON INHIBITORS
Ø NaHCO3 reabsorption is initiated by: NaHCO3 –
Na/H exchanger (NHE3)
Ø Carbonic anhydrase inhibitors: block NaHCO3
reabsorption
Ø Adenosine receptor antagonist: blocks NaCl
reabsorption
LOOP OF HENLE
Ø Pumps Na, K and Cl out of the lumen into the
interstitium
Ø Provides the concentration gradient for the
countercurrent concentrating mechanism
Ø Diluting segment: thick ascending limb of the loop of
Henle
Ø Ca and Mg reabsorption
Ø Na/K/2Cl cotransporter (NKCC2)
Overview
I. Introduction
II. Renal Transport System
III. Renal Autacoids
IV. Basic Pharmacology of Diuretic Agents
V. Agents that Alter Water Excretion
(Aquaretic s)
VI. Clinical Pharmacology of Diuretic Agents
Sodium bicarbonate reabsorption by the PCT is initiated by
the action of a Na+/ H+ exchanger (NHE3) located in the
luminal membrane of the proximal tubule epithelial cell.
This transport system allows Na+ to enter the c ell from the
tubular lume n in exc hange for a proton (H+) from ins ide the
cell. As in all portions of the nephron, Na+/K+-ATPase in the
basolateral membrane pumps the reabsorbed Na+ into the
interstitium in order to maintain a low intracellular Na+
concentration. The H+ secreted into the lumen combines
with bicarbonate (HCO3-) to form H2CO3 (carbonic ac id),
which is rapidly dehydrated to CO2 and H2O by carbonic
anhydrase. Carbon dioxide produced by dehydration of
H2CO3 enters the proximal tubule cell by simple diffusion,
where it is then rehydrated back to H2CO3, facilitated by
intracellula r carbonic an hydrase. A fter dissoc iation of
H2CO3, the H+ is ava ilable for transport by the Na+/H+
exchanger, and the HCO3- is transpo rted out of the cell by
a basolateral membrane transporter
