Download USMLE Step 1 Web Prep — Diuretics Pt. II 145510 >>> 0:00:01

USMLE Step 1 Web Prep — Diuretics Pt. II
145510 >>> 0:00:01
SLIDE 1 of 6
Fig III-15. Actions of Thiazides on the Distal Convoluted Tubule (DCT)


Inhibit Na+/Cl- cotransporter on luminal membrane of DCT.
Normally, Na+ is exchanged for K+ via a “pump” on basolateral membrane, K+
returns to blood by back-diffusion. Ca2+ diffuses across luminal membrane
via channels (PTH regulated) & returns to blood by a Ca2+/Na+ antiporter

Inhibition of the Na+/Cl- cotransporter
luminal levels
hypokalemia &
alkalosis occur consequent to the Na+ load “downstream”.


activity of Ca2+/Na+ antiporter
Thus, thiazide diuretics
of Ca2+.
reabsorption of Ca2+
hypercalcemia.
urinary levels of Na+, K+ & Cl-, but
urinary levels
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SLIDE 2 of 6
Thiazides



Hydrochlorothiazide, indapamide, metolazone are organic acids, both filtered &
secreted in the proximal tubule.
Rx uses: HTN & CHF (proven longterm efficacy), edematous states (+/- loops)
including pulmonary edema, nephrolithiasis & diabetes insipidus (ADH
resistance or lithium-induced).
Adverse effects:allergies, alkalosis, hypokalemia, hypercalcemia,
hyperuricemia, hypovolemia, hyperglycemia, hyperlipidemia (
not indapamide) & sexual dysfunction.
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LDL-C & TGs,
SLIDE 3 of 6
Fig III-16. Actions of Potassium Sparing Agents on Collecting
Tubules

CT determines final urinary Na+ concentration and secretes K+ & H+.

Normally, aldosterone
(principal cell) and
formation of Na+ channels on luminal membrane
activity of Na+/K+ & H+ exchangers.

Na+ entry

Na+ entry
energy-dependent extrusion of H+ across luminal membranes
(intercalated cell).
The aldosterone receptor antagonist & Na+ channel blockers prevent above
effects
minor effects on Na+ reabsorption, but major effects on retention of
K+ ions & protons.


intracellular +ve charge
Thus, K-sparing agents cause small
& H+ (hyperkalemia & acidosis).
extrusion of K+ into the lumen.
urinary Na+, but marked
in urinary K+
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SLIDE 4 of 6
+
K Sparing Agents




Spironolactone, amiloride & triamterene are weak diuretics, since most of
filtered Na+ is reabsorbed before reaching the CT.
Rx uses of spironolactone: hyperaldosteronism, adjunctive with other diuretics
in HTN & CHF, antiandrogenic uses (eg, female hirsutism).
Rx uses of Na+ channel blockers: adjunctive with other diuretics in HTN & CHF
to decrease K+ loss, lithium-induced diabetes insipidus (amiloride)
Adverse effects: acidosis, hyperkalemia, azotemia, gynecomastia & libido
changes (spironolactone), nephrolithiasis (triamterene).
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SLIDE 5 of 6
Table III-6. Modes of Action and Effects of Diuretics (A)
Drug
Mechanisms
of Action
acetazolamide Inhibit carbonic
anhydrase in
PCT
Urinary
Blood Chemistry &
Electrolytes
pH
Na+
hypokalemia,
K+
acidosis ( pH)
Ca2+
HCO3
PO4
ethacrynic acid, Inhibit
furosemide
Na+/K+/2Clcotransporter in
TAL
Na+
K+
Ca2+
hypokalemia,
alkalosis ( pH),
hypomagnesemia
Mg2+
ClHCO3
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SLIDE 6 of 6
Table III-6. Modes of Action and Effects of Diuretics (B)
Drug
Thiazides
Mechanisms of
Action
inhibition of Na+/Clcotransporter in PCT
Urinary
Electrolytes
Blood
Chemistry &
pH
Na+
hypokalemia,
K+
alkalosis (
pH),
hypercalcemia
ClCa2+
Amiloride &
block Na+ channels
triamterene,
block
spironolactone aldosteronereceptors
in CT
Na+ (small) hyperkalemia,
acidosis ( pH)
K+
H+