Diuretics Flashcards

1
Q

Proximal Tubule Absorption

A
  • Sodium chloride (active transport), water (passive transport), others (sodium bicarbonate glucose, amino acids, glucose); site of action of acetazolamide (CA inhibitor) and mannitol (osmotic diuretic)
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2
Q

Loop of Henle Absorption

A
  • Water is reabsorbed (osmotic forces) in the descending thin segment; site of action of mannitol. NaCl is reabsorbed (35%) in the thick segment and is impermeable to water; site of action of furosemide (loop diuretic), a Na/K/Cl cotransporter inhibitor.
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3
Q

Distal Convuluted Tubule Absorption

A
  • Approximately 10% of filtered NaCl is reabsorbed in the distal convoluted tubule and is relatively impermeable to water; site of action of Hydrochlorothiazide (thiazide), a Na/Cl co-transport inhibitor.
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4
Q

Collecting Tubule Absorption

A
  • Approx. 2-5% of filtered NaCl is reabsorbed in the collecting tubule; site of action of potassium-sparring diuretics, spironolactone (aldosterone receptor blocker) and amiloride (Na channel blocker). Collecting tubule is also the site of action of conivaptan (AntiDiuretic Hormone receptor antagonist), demeclocycline (AntiDiuretic Hormone cAMP antagonist) and mannitol.
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5
Q

Major diuretic drugs which have been found to induce diuresis

A
  • Carbonic anhydrase inhibitors
  • Osmotic diuretics
  • Loop diuretics
  • Thiazides
  • Potassium-sparring diuretics
  • Antidiuretic hormone (ADH) antagonists
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6
Q

Carbonic Anhydrase Inhibitors

A
  • Acetazolamide
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7
Q

Acetazolmide MOA

A
  • Carbonic anhydrase inhibitors
  • Inhibition of bicarbonic reabsorption
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8
Q

Acetazolamide Pharmacodynamics

A
  • Carbonic Anhydrase Inhibitor
  • Diuretic efficiency decreases significantly over several days due to enhanced NaCl reabsorption by the remainder of the nephron.
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9
Q

Acetazolamide Pharmacokinetics

A
  • Carbonic Anhydrase Inhibitor
  • Good oral bioavailability; diuresis is apparent within 30min., persists for 12hrs. after single dose, drug elimination by proximal tubule segment.
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10
Q

Acetazolamide Adverse Reactions

A
  • Hyperchloremic metabolic acidosis
  • Renal stones
  • Renal potassium wasting
  • Other toxicities: hypersensitivity reactions
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11
Q

Acetazolamide Therapeutic Uses

A
  • Glaucoma- decreases aqueous humor and intraocular pressure
  • Urinary alkalinization- enhance excretion of weak acids
  • Metabolic alkalosis- diuretic therapy (w/ loop diuretics) during heart failure
  • Acute mountain sickness
  • Other uses: adjuvants for epilepsy
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12
Q

Osmotic Diuretics

A
  • Mannitol
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13
Q

Mannitol MOA

A
  • Osmotic Diuretics
  • Prevents normal water reabsorption in the proximal tubule, descending limb of the loop of henle and collecting tubule due to osmotic forces. Also opposes the action of ADH in the collecting tubule.
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14
Q

Mannitol Pharmacokinetics

A
  • Osmotic Diuretic
  • Poorly absorbed, must be given parentarally
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15
Q

Mannitol Adverse Reactions

A
  • Osmotic diuretic
  • Extracellular volume expansion, may complicate heart failure and produce pulmonary edema
  • Dehydration and hypernatremia
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16
Q

Mannitol Therapeutic Uses

A
  • Osmotic diuretic
  • Reduction of intracranial and intraocular pressure
  • To increase urine volume
17
Q

Loop Diuretics

A
  • Furosemide
18
Q

Furosemide MOA

A
  • Loop diuretic
  • Inhibit Na/K/Cl transporter in the thick ascending limb of loop of Henle
19
Q

Furosemide Adverse Effects

A
  • Hypokalemic metabolic alkalosis
  • Ototoxicity
  • Hyperuricemia
  • Hypomagnesemia
  • Allergic reactions
  • Other toxicities: dehydration
20
Q

Furosemide Therapeutic Uses

A
  • Loop diuretic
  • Hyperkalemia
  • Acute renal failure
  • Anion overdose
  • Other uses: heart failure; severe hypertension
21
Q

Thiazides

A
  • Hydrochlorothiazide
22
Q

Hydrochlorothiazide MOA

A
  • Thiazide
  • Inhibit NaCl reabsorption in the distal convoluted/collecting tubules by blocking the Na+/Cl- transporter
  • Enhance Ca2+ reabsorption
23
Q

Hydrochlorothiazide Adverse Effects

A
  • Hypokalemic metabolic alkalosis and hyperuricemia
  • Impaired carbohydrate tolerance
  • Hyperlipidemia
  • Hyponatremia
  • Allergic reactions
  • Other toxicities: weakness, fatigability
24
Q

Hydrochlorothiazide Therapeutic Uses

A
  • Hypertension
  • Heart failure
  • Nephrolithiasis due to idiopathic hypercalciuria
  • Nephrogenic diabetes insipidus
25
Q

Potassium-sparring diuretics

A
  • Spironolactone
  • Amiloride
  • Triamterne
26
Q

Potassium-sparring diuretics MOA

A
  • Competitive antagonist to aldosterone at the late distal tubule and cortical collecting tubule
  • Spironlactone inhibit mineralocorticoid (aldosterone) receptors
  • Amiloride inhibit of Na influx
27
Q

Potassium-sparring Diuretics Adverse Effects

A
  • Hyperkalemia
  • Hyperchloremic metabolic acidosis
  • Gynecomastia
  • Acute renal failure
  • Kidney stones
28
Q

Potassium-sparring Diuretics Therapeutic Uses

A
  • Mineralcorticoid excess due to primary hypersecretion (Conn’s syndrome) or to secondary aldosteronism (from heart failure, hepatic cirrhosis, nephrotic syndrome, and other conditions assoc. w/ diminished effective intravascular volume); hypertension
29
Q

Antidiuretic Hormone (ADH) Antagonists

A
  • Conivaptan, IV, PO adm
  • Demeclocycline, PO adm
30
Q

Antidiuretic Hormone (ADH) Antagonists MOA

A
  • Inhibit the effects of ADH in the collecting tubule
  • Reduce cyclic AMP production (demeclocycline)
  • V1A and V2 ADH receptor blocker (conivaptan)
31
Q

Antidiuretic Hormone (ADH) Antagonists Adverse Effects

A
  • Nephrogenic diabetes insipidus (demeclocycline)
  • Renal failure (demeclocycline)
  • Other: demeclocycline should be avoided in pts. w/ liver diseases and in children younger than 12 years
  • Hypokalemia (conivaptan)
  • Injection site rxns. (conivaptan)
32
Q

Antidiuretic Hormone (ADH) Antagonists Therapeutic Uses

A
  • Syndrome of inappropriate ADH secretion (SIADH)
  • Other causes of elevated antidiuretic hormone
  • Conivaptan is currently being evaluated in clinical studies for use in CHF
33
Q

Nephrone Absorption Illustration

A