Exam 1 - Diuretics Flashcards
What are the thiazide diuretics?
Indapamide (lozol)
Metolazone (zaroxolyn)
HCTZ (esidrix, hyrdrodiuril)
Chlorthalidone (hygroton)
Chlorothiazide (diuril)
(I Might Have Chocolate Cake)
what are the loop/high ceiling diuretics?
Bumetanide (bumex)
Furosemide (lasix)
Torsemide (demadex)
what are the K+ sparing diuretics?
Amiloride (midamor)
Triamterene (Dyrenium)
Eplerenone (inspra)
Spironolactone (aldactone)
(ATES)
what are the functional zones along the nephron in order?
Bowman’s capsule
Proximal convoluted tubule
Descending loop of Henle
Ascending loop of Henle
Distal convoluted tubule
Collecting tubule and duct
(Buying Party Drugs All Day? Cool)
what 4 things happen in regulation of fluids by the kidney?
Glomerular filtration
Tubular reabsorption
Tubular secretion
Water conservation
(Going Water Tubing Today)
glomerular filtration
generates a plasma like filtrate of blood
tubular reabsorption
Active reabsorption of ions to remove useful solutes from the filtrate
Returns them to the blood
tubular secretion
secretion of ions to remove additional wastes from the blood and add them to the filtrate
water conservation
passive reabsorption of water to remove water from the urine and returns it to the blood, waste concentrate
what is the site of action of thiazide diuretics?
distal convoluted tubule (DCT) on the luminal membrane
what is the molecular target of thiazide diuretics?
Na+/Cl- cotransporters
~10% of coupled reabsorption of Na+ and Cl-
why are thiazides called low ceiling diuretics?
increasing the dose above the therapeutic dose does not have more diuretic response
what are the adverse effects of thiazides?
Renin secretion due to volume and Na+ depletion
what is the MOA of thiazides?
Inhibition of thiazide sensitive Na+/Cl- cotransporter on luminal membrane of DCT — causes decreased reabsorption of Na+
Decreases [Na+]
Increases water excretion
Low plasma volume
Low CO and renal blood flow
Lowers BP
thiazides must be excreted into the ___ to be effective
tubular lumen
if a pt w/ decreased renal function takes a thiazide, there is ___ efficacy
lower
what are the adverse effects of thiazides?
Hypokalemia
Hypotension
Hypercalcemia
Hyperuricemia
Hyperglycemia (in some patients)
(2 hypos and 3 hypers)
why can thiazides cause hypokalemia?
increased K+ excretion due to the stimulation of the aldosterone hormone
Why can thiazides cause hypercalcemia?
They increase Ca2+ reabsorption
HCTZ is a ____ agent, while chlorthalidone, indapamide, and metolazone are ____ agents
HCTZ = thiazide type
Others = thiazide like
when should loop diuretics be dosed? Why?
in the morning to avoid nocturnal diuresis
are thiazides or loop diuretics typically more effective in most patients?
thiazides
Why should the usual doses of thiazides be used?
to avoid adverse metabolic effects
which thiazides are preferred?
HCTZ
Chlorthalidone
Indapamide
What comorbidity can thiazides have additional benefits in? What should it be avoided in ?
Additional benefits in osteoporosis
Avoid in gout
What is the site of action of loop diuretics?
ascending limb of loop of henle
what is the molecular target of loop diuretics?
Na+ / K+ / 2Cl- cotransporter
what is the MOA of loop diuretics?
inhibits cotransport of Na+ / K+ / 2Cl- in the luminal membrane
Potent diuresis because 25-30% of NaCl is reabsorbed here
loop diuretics ____, even in pts w/ poor renal function
act promptly
Loop diuretics are called ___ and are the ____
high ceiling, most powerful
when should loop diuretics be dosed? why?
In the morning
If taking BID, second dose should be In the late afternoon
To avoid nocturnal diuresis
when may higher doses of loop diuretics be needed?
for pts w/ severely decreased glomerular filtration rate (GFR) or heart failure
In what patient group are loop diuretics preferred over thiazides?
Concominant renal dysfunction
Resistant HTN
What is the site of action of K+ sparing diuretics?
collecting tubule
what is the MOA of K+ sparing diuretics?
Inhibit Na+ reabsorption without K+ excretion
Spares K+
What are the classes of K+ sparing diuretics?
Aldosterone antagonists
Sodium channel (ENaC) blockers
which of the K+ sparing diuretics are aldosterone antagonists?
Spironolactone (aldactone)
Eplerenone (inspra)
which of the K+ sparing diuretics are ENaC blockers?
Amiloride (midamor)
Triamterene (dyrenium)
what do aldosterone antagonists cause?
Loss of Na+ and water
Hyperkalemia
Some acidosis risk
What is the MOA of aldosterone antagonists?
Competes w/ aldosterone for aldosterone receptors (antagonizes them)
Forms inactive spironolactone-aldosterone sensitive Na+ transporter (only a small fraction of K+ exchanged through this transporter)
Increases Na+ loss without significant K+ loss
Decreases blood volume, CO, BP
what is aldosterone?
steroid hormone secreted by zona glomerulosa
Promotes retention of Na+ and water
what is the site of action of ENaC blockers?
collecting duct
what is the MOA of ENaC blockers?
Block ENaC
Decreases Na+ / K+ exchange
K+ sparing diuretic without depending on aldosterone
what do epithelial Na+ transport channels (ENaC) do?
cause Na+ reabsorption (saving Na+) in exchange for K+ (lost in urine)
what are the AEs of Na+ channel blockers?
triamterene increases:
- uric acid (why they’re a problem in gout)
- renal stones
- K+ retention
K+ sparing diuretics are generally used in combination with a ____. Why?
Thiazide
To minimize hypokalemia
K+ sparing diuretics do not significantly lower BP unless used w/ a ___
thiazide
what pts should K+ sparing diuretics be generally reserved for?
those experiencing diuretic induces hypokalemia
K+ sparing diuretics should be avoided in pts with ___
CKD
K+ sparing diuretics may cause hyperkalemia, especially when combines with what drugs?
ACEi
ARB
Direct renin inhibitor
K+ supplements
when should aldosterone antagonists be dosed?
Morning
Second dose in late afternoon if BID
To avoid nocturnal diuresis
Eplerenone is contraindicated in patients with:
CrCl < 50 mL/min
Elevated SCr
Type 2 DM w/ microalbuminuria
what aldosterone antagonist is often used as add on therapy in resistant HTN?
spironolactone
Spironolactone is to be avoided in what pts?
CKD
Aldosterone antagonists may cause hyperkalemia, especially when taken in combo with:
ACEi
ARB
Direct renin inhibitor
K+ supplements
What drug is a carbonic anhydrase inhibitor?
acetazolamide
what is the site of action of carbonic anhydrase inhibitors?
proximal convoluted tubule (PCT)
what is the MOA of carbonic anhydrase inhibitors?
Inhibits carbonic anhydrase, which catalyzes reaction
Inhibits HCO3- transport out of PCT and into the interstitium
Less Na+ reabsorption
Greater loss of: Na+, HCO3-, and water
what drugs are osmotic diuretics?
Mannitol
Urea
what is the MOA of mannitol?
Draws free water out of tissues (including brain) and into IV space
Can transiently decrease cerebral edema (until excreted by kidneys)
Freely filtered in glomerulus, cannot be absorbed
Remains in lumen and lowers osmotic pressure
Water follows into lumen mannitol due to pressure
Does not reabsorb, causing osmolarity of fluid in tubules to increase
Prevents water reabsorption
Osmotic diuresis
(Don’t Cry For Real — We Don’t Pity Ourselves)
what is the pharmacological action of osmotic diuretics?
- Reduction of intracranial pressure and brain volume
- Reduction of intraocular pressure
- Increased urine volume
- Increased Na+ retention
What is the weakest of the diuretics? What can it cause?
Carbonic anhydrase inhibitors
Mild diuresis
