DIURETICS

Question 1

Furosemide

Answer 1

Loop diuretic

Inhibits NaCL reabsorption in TAL by inhibiting NKCC2 (Na+/K+/2Cl- cotransporter).

Most efficacious diuretic agents currently available (aka high ceiling-diuretics)

Also diminishes the lumen-positive potential that comes from K+ recycling, leading to an increase in Mg+ and Ca2+ excretion.

Increases the urinary excretion of K+ and ur UC acid (d/t enhanced exchange of Na+ and K+ in the DCT) —> predisposes individual to HYPOkalemia and metabolic alkalosis.

USES: management of edema associated w/ heart failure, hepatic or renal disease; acute plum edema and in the treatment of HTN (alone or in combinations w/ another thiazide)

ADVERSE EFFECTS: ototoxicity, hypokalemia (can cause cardiac arrhythmia), hypochloremic alkalosis (d/t inc excretion of K+ and H+), hypomagnesmia, hypocalcemia, acute hypovolemia, hyperuricemia (can precipitate gout), hyperglycemia, hyperlipidemia, photosensitivity, parasthesias, bone marrow depression and GI disturbances.

Question 2

Hydrochlorothiazide,
Chlorthalidone,
Metolazone

Answer 2

Thiazide diuretics

Inhibit NaCl reabsorption in the DCT by blocking the Na+/Cl- cotransporter (NCCT)

Increase the reabsorption of calcium —> helpful in the treatment of recurrent kidney stones d/t hypercalcuria

USES: management of mild-to-moderate hypertension *preferred choice of antihypertensives in black/elderly patients who may not respond well to treatment with either ACEI’s or ARB’s.

Can be administered orally and may take 1-3 weeks to produce a stable drop in BP.

ADVERSE: hypokalemia, hyponatremia, hyperuricemia, hypercalcemia, hyperglycemia, hyperlipidemia, hypersensitivity (photosensitivity, generalizes dermatitis), sexual dysfunction

Question 3

Spironolactone, Eplerenone

Answer 3

Potassium sparing diuretics - aldosterone antagonists

Prevent K+ secretion by antagonizing the effects of aldosterone at the late distal and cortical collecting tubules

The clinical efficacy of aldosterone antagonists is a function of endogenous levels of aldosterone. The higher the levels of aldosterone, the greater the effects of the antagonists on urinary excretion.

USES: primarily in the management of edema associated with excessive aldosterone excretion or with CHF; HTN; primary hyperaldosteronism, hypokalemia, liver cirrhosis accompanied by edema or ascites and nephrotic syndrome, management of severe HF to increase survival and reduce hospitalizations when added to standard therapies.

ADVERSE EFFECTS: hyperkalemia, gastric upset and peptic ulcers, endocrine effects (antagonistic effects on other steroid (androgen) receptors, can cause gynecomastia, impotence, decreases libido, deepening of voice and menstrual irregularities), hyperchloremic metabolic acidosis, CNS effects (tears) include drowsiness, lethargy, headache and confusion.

Question 4

Amiloride,

Triamterene

Answer 4

Potassium sparing diuretics- Inhibitors of Renal Epitheilial Na+ channels (ENaC) in the late distal tubule and collecting duct

ADVERSE EFFECTS: Hyperkalemia, hyponatremia
Triamterene can also reduce glucose tolerance and induce photosensitization and has been associated with interstitial nephritis and renal stones.

Question 5

Acetozolamide

Answer 5

Carbonic anhydrase inhibitor

Inhibit both extra- and intra- cellular forms of CA, resulting in reduction of HCO3- reabsorption in PCT.

USES: mainly used for its pharmacological properties other than its diuretic properties: glaucoma, mountain sickness, metabolic alkalosis, epilepsy

ADVERSE EFFECTS: hyperchloremic metabolic acidosis, hyponatremia, hypokalemia, renal stones, other: malaise, fatigue, depression, drowsiness

Question 6

Mannitol

Answer 6

Osmotic Diuretic

Administered in large enough doses to significantly inc the osmolality of plasma and tubular fluid —> expand the ECF volume, decrease blood viscosity, and inhibit renin release; inc urinary excretion of nearly all electrolytes.

USES: reduction of increased ICP associated w/ cerebral edema, reduction of intraocular pressure, urinary excretion of toxic substances

ADVERSE: extracellular volume expansion and hyponatremia, tissue dehydration

CONTAINDICATIONS: pts w/ active intracranial bleeding

Question 7

Conivaptan

Answer 7

ADH Antagonists

Inhibits effects of ADH in CD by antagonizing V1 and V2 receptors —> CD remains impermeable to water and dilute urine is produced

USES: euvolemic and hypervolemic hyponatremia in hospitalized patients; SIADH

ADVERSE: nephrogenic diabetes insipidus, infusion site reactions, AF, GI & electrolyte disturbances

CONTRAINDICATIONS: hypovolemic hyponatremia, renal failure