Bahouth: Diuretics and Aquaretics Flashcards
What is the main reason to use diuretics?
To mobilize sodium (to urinate)
Where does carbonic anhydrase (CA) act in the nephron?
PCT (90%)
DCT (10%)
What does CA do?
converts H2CO3 to H20 + CO2 (and vice versa)
What are the net effects of CA inhibitors?
- bicarbonate loss in urine
- alkaline urine
- enhanced chloride reabsorption (acidosis)
What are clinical uses of CA inhibitors?
- to akalinize urine in pts with cysteinurea
- to reduce intraocular pressure (used pre-operatively for glaucoma surgery)
- prophylactic tx of mountain sickness
What is an example of a CA inhibitor?
Acetazolamide
What are side effects of CA inhibitors?
- metabolic acidosis (bc of increased Cl- reabsorption)
- increased K+ loss in urine (acute effect)
What are characteristics of osmotic diuretics?
- small molecules (filterable)
- not reabsorbed
- inert
- not metabolized
What is the MOA of osmotic diuretics in the PCT (minor role)?
osmotically inhibit Na+ and H20 reabsorption (bc it increases tubular osmolarity)
What is the MOA of osmotic diuretics in the Loop of Henle (major role)?
- increase the osmolarity of plasma
- which extracts H20 from peripheral tissues and decreases blood viscosity
- which increases medullary RBF and reduces its tonicity
- impaired water reabsorption by thin DLH
- impaired NaCL and urea extraction by thin ALH
What is the net effect of osmotic diuretics?
significantly increase urine (this class increases volume of urine the most) with small increments of NaCL
what are clinical uses of osmotic diuretics?
- tx of dialysis disequilibrium syndrome
- reduce intra cranial pressure (from head trauma)
- reduce intraocular pressure
What is an example of an osmotic diuretic?
Mannitol (a sugar alcohol)
what are side effects of osmotic diuretics?
volume overload
What is a contraindication of osmotic diuretics?
cardiac failure
What are the MOAs of loop diuretics?
- inhibit Na-K-2Cl symporter in TALH
- inhibits ability of MD to sense NaCl
- stimulates biosynthesis of prostaglandins
- increases total RBF (by relaxing the afferent and efferent arterioles)
- Maintains GFR
- potently increases renin release
How do loop diuretics potently increase renin release?
by 1. inhibiting the MD
- reflexely activating the sympathetic NS
- stimulating intrarenal baroreceptor mechanisms
Why are loop diuretics also called high-celing diuretics?
be “the loss of Na+ hits the roof” (the dude said it)
T or F: Loop diuretics are the most potent class of diuretics in mobilizing NaCl
T
What are the net effects of loop diuretics?
- copious diuresis with significant NaCl loss
- increased urinary excretion of K+/H+
- increased excretion of Ca2+ and Mg2+
- impairs the ability of kidney to concentrate urine
What are the therapeutic uses of loop diuretics?
- Edema (cardiac, hepatic, or renal)
- pulmonary edema due to LV failure
- hypercalcemia (via mobilization of Ca2+)
- protection against renal failure
- washout of toxins (by increasing urine flow)
- increase effectiveness of other antihypertensives by causing diuresis
What are some examples of loop diuretics?
FUROSEMIDE
Bumetanide
Torsemide
What is the MOA of furosemide? what is unique about its MOA?
inhibits NaCl reabsorption in the TALH by inhibiting the Na+/K+/2Cl- symporter
it must be secreted into the PCT lumen and travel in the lumen to the TALH to inhibit the luminal transporter
What are the pharmacological effects of furosemide?
- copious diuresis with significant NaCl loss
- increased excretion of K+/H+
- increased excretion of Ca2+ and Mg2+
- increased PG synthesis
- increased venous capacitance (venodilation)
Furosemide normal dose? time to diuretic response? t1/2? protein binding? elimination?
20-40 mg BID 30 mins short t1/2: 1.5 hrs extensive protein binding (~80%) renal (65% excreted in urine)
side effects of furosemide?
- hyopkalemia
- alkalosis
- elevated BUN, hyperglycemia, hyperuricemia
- ototoxicity (reversible)
- sialadentitis (inflammation of salivary glands)
drug interactions with furosemide?
- Lithium
- indomethacin (a PG inhibitor)
- probenecid (inhibits secretion of furosemide into tubular fluid)
- warfarin (99% protein bound, could be displaced by furosemide and lead to toxicity)
Advantages of Bumetanide over furosemide? Substituted for furosemide in what kind of patients?
40x more potent
those receiving warfarin
Advantages of torsemide over furosemide? Other effects?
- a long-acting loop diuretic –>once daily dosing)
- antihypertensive (decreases BP)
