Diuretics Flashcards
Diuretics
increase urine production by acting on the kidney (Pig. 3.1). Most agents
affect water balance indirectly by altering electrolyte reabsorption or secretion. Osmotic agents
affect water balance directly.
NAtiuretic Diuretics
produce diureaia, associated with increased sodium (N1+)
excretion, which results in a concomitant loss of water and a reduction in extracellular volume
Adverse effects
Hypo-kalemia, natremia, chloremia and acid-base disturbances
Carbonic Anhydrase inhibitors
Acetezolamide
Dichlorphenamide
Methazolamide
CAI MOA
Carbonic Anhydrase of PCT is reversibly inhibited leading to reduced absorbtopn of sodium and bicarb- increase excretion of Na, HCO3 and H2O
Indications of CAI
Rarely used as diuretis
Indicated in reducing ocular pressure in glaucoma
alkaline urine to enhance uric acid and cystine secretion
Acute mountain sickness prophylaxis
Adjuvant therapy for Epilepsy
Adv Eff and ContraI
Metabolic acidosis- depletion of HCO3, decrease in Ca and risks formation if calculi, K+ wasting
drowsiness and parasthesia
precaution in Sulfa allergy as they are sulfonamide derivatives
contraindicated in cirrhosis
Loop diuretics
furosemide, bumetanide, torsemide, and ethacrynic acid
MOA of LD
Loop diuretics Inhibit active sodium chloride (NaCl) reabsorption in the
thick ascending limb of the loop of Henle by inhibiting the activity of NAKCC2 symporter.
Diuresis occurs in 5min after administration IV and 30 min oral
why are Loop diuretics referred as high ceiling
Because of the high capacity for NaCl reabsorption in this segment, agents active at this
site markedly increase water and electrolyte excretion
LD also reduces the
lumen positive potential, mg+2 and Ca excretion is increased
The block the kidney’s ability to concentrate urine by interfering with an important step in
the production of a hypertonic medullary interstitium.
Loop diuretics cause increased renal prostaglandin production, which accounts for some of
their activity. Nonsteroidal anti-inftammatory drugs (NSAlDs) can reduce the effectiveness
of loop diuretics.
Uses for LD
CHF- reduces acute PE when along with Thiazides
treat hypertension in renal failure patients
acute hypercalcemia due to hyper PTH or malignancy
Adv eff of LD
a. Loop diuretics produce hypotension and volume depletion.
b. They can cause hypokalemia due to enhanced secretion ofK+. They may also produce alkalo1i1 due to enhanced H• secretion. Mgz+ wasting can occur with chronic use.
The risk of cardiac glycoside (digoxin) toxicity increases in the presence of hypokalemia.
Loop diuretics can cause dose-related ototoxicity, more often in individuals with renal impairment. These effects are the most pronounced with ethacrynic acid.
These agents should be administered cautiously in the presence of renal disease or with the use of other ototoxic agents, such as aminoglycosides.
All loop diuretics, except ethacrynic acid, are
Sulfonamides- caution in sulfa allergy
Thiazide and thiazide-like diuretics
chlorothiazide and hydrochlorothiazide. Chlorothiazide is the only
thiazide available for parenteral use.
Thiazide-like drugs
Metolazone, chlorthalidone, and indapamide
They have properties similar to thiazide diuretics but may be effective in the presence
of renal impairment.
MOA of TZD
Thiazide diuretics inhibit active re. absorption of NaCl in the distal
convoluted tubule by blocking the NCC cotransporter
This results in the net
excretion of sodium and an accompanying volume of water. Diuresis occurs within 1 to 2 hours
a. They decrease the diluting capacity of the nephron.
b. These agents increase excretion of Na+, Cl-, K+, and, at high doses, bicarbonate (HC03 -). They
also reduce excretion of Ca+
Uses of TZDs
TZDs inhibit NaCl reabsorption in DCT by blocking NCC.
diuresis occurs in 1-2 hours
decrease the diluting capacity of the nephron.
These agents increase excretion ofNa+, Cl-, K+, and, at high doses, bicarbonate (HC03 -). They also reduce the excretion of Ca
Adv eff of TZDs
a. Thiazide diuretics produce electrolyte imbalances such as hypokalemia, hyponatremia, and
hyperalcemia. Potassium supplementation may be required.
b. The risk of cardiac glycoside (dlgoxin) toxicity increases in the presence of hypokalemia.
c. These agents often elevate Serum urate, presumably as a result of competition for the organic anion carriers (which also eliminate uric acid). Gout-like symptoms may appear
d. Thiazide diuretics can cause hyperglycemia (especially in patients with diabetes), hypertriglyceridemia, and hypercholesterolemia.
e. These agents are sulfonamide derivatives; therefore, precaution must be used in patients with a sulfa allergy
K+ Sparing
spironolactone, eplerenone, amiloride, and triamterene
MOA of K+ sparing
Potassium-sparing diuretics reduce Na+ reabsorption and K excretion by antagonizing the
effects of aldosterone In the collecting tubule.
Spironolactone and Eplerenone inhibit the actions of
aldosterone- binds to mineralocorticoid receptor and prevents subsequent cellular events of K+ and H+ secretion and Na+ reabsorption
An important action is a reduction in the blo·synthesis of epithelial Na• channel (ENaC) in the principal cells of the collecting duct
These K+ agents are active only when
endogenous mineralocorticoid is present; the effects
are enhanced when hormone levels are elevated.
