Diuretics

Question 1

What is the mechanism of action of Acetazolamide?

Answer 1

• Inhibits carbonic anhydrase-> acts predominantly in the proximal tubule by blocking sodium bicarbonate reabsorption-> affecting the NHE3 exchanger that allows Na+ to enter the cell,dependent upon the H+ produced through carbonic anhydrase
• Excretion of drug is by tubular secretion in proximal tubule
• effectiveness -> decreases significantly over several days-> enhanced NaCl absorption due to bicarbonate depletion

Question 2

What are the pharmacodynamics of carbonic anhydrase inhibition?

Answer 2

Causes significant bicarbonate losses resulting in hyperchloremic metabolic acidosis

Question 3

What are the therapeutic uses for carbonic anhydrase inhibitors?

Answer 3

• Eye: glaucoma-> decreases production of aqueous humor (Dorzolamide & brinzolamide)
• Acute mountain sickness
• To correct metabolic alkalosis
• Alkalinize the urine
• Anticonvulsant properties

Question 4

Adverse effects of carbonic anhydrase inhibitors

Answer 4

Paraesthesias, somnolence, allergic reactions-sulfonamides, renal K+ wasting
-Contraindications: Hepatic cirrhosis

Question 5

Describe Mannitol and MOA

Answer 5

• Osmotic diuretic
• Act in the proximal tubule and descending limb of henle’s loop
• Initially expand the extracellular fluid volume, decrease blood viscosity, and inhibit renin release.
• poorly absorbed-> give parenterally
• Orally: osmotic diarrhea -> eliminate toxic substances from GI tract

Question 6

What are the clinical indications of an osmotic diuretic?

Answer 6

• To increase water excretion in preference to sodium excretion
• Reduction of intracranial and intraocular pressure
• To promote prompt removal of renal toxins w/ charcoal

Question 7

Adverse effects of Osmotic diuretics

Answer 7

• Extracellular volume expansion->(before diuresis) hyponatremia-> complicates congestive heart failure -> pulmonary edema
• Headache, nausea, and vomiting
• Dehydration and hypernateremia (after diuresis)

Question 8

Describe loop diuretics

Answer 8

oBlocks the NKCC on the luminal membrane of the TAL (furious kid keeping the peanuts on the ride)
oBy blocking the NKCC, loop diuretics reduce the lumen positive potential, promoting the excretion of Mg2+ and Ca2+ (Furious kid clinging to magnets and calci-yum ice cream)

Question 9

What are the ADH antagonists?

Answer 9

• Vaptans

- Conivaptan, tolvaptan

Question 10

Why do we use Vaptans?

Answer 10

• Treatment of euvolemic hyponatremia
• Conivaptan-antagonist @ v1a and V2 receptors
• Lixivaptan and tolvaptan-> against the V2 receptor

Question 11

What are ADH antagonists used for?

Answer 11

• Syndrome of inappropriate ADH secretion

- Other cases of elevated ADH-> heart failure or liver disease

Question 12

ADH antagonist toxicity

Answer 12

• Nephrogenic diabetes insipidus -> can be treated with a thiazide diuretic or amiloride
• renal failure
• tremulousness, mental obtundation, cardiotoxicity, thyroid dysfunction, and leukocytosis
• Demeclocycline should be avoided in patients with liver disease