Diuretics

Question 1

Furosemide

Answer 1

Class: Loop diuretic
Location: Ascending loop of Henle
Route: oral & parenteral
t1/2 = 2-4h

MOA:

• Block NKCC2 cotransporter
• Inc. Na/Cl/K in tubular fluid
• Inc. H2O excretion

Use(s):

• Edema: (DOC)
  
  • heart failure
  • hepatic or renal disease
• HTN (moderate - severe)

Actions:

• Inc. urine output
• Inc. K excretion
• Inc. Ca excretion
• Inc. Mg excretion
• Inc. prostaglandin synthesis
• Dec. renal vascular resistance
• Inc. renal blood flow

Adverse Effects:

• Ototoxicity
• Hyperuricemia
• Acute hypovolemia
• Hypokalemia
• Hypomagnesemia
• Allergic reactions (sulfadrug)

Question 2

Hydrochlorothiazide
Chlorthalidone
Metolazone

Answer 2

Class: Thiazide
Location: Distal tubule
Route: oral
t1/2 = 40h

MOA:

• Block NCCT cotransporter
• Inc. Na/Cl tubular fluid
• Inc. H2O excretion

Use(s):

• HTN
• Heart failure
• Hypercalciuria
• Diabetes insipidus
• Premenstral edema

Action(s):

• Inc. Na/Cl exretion
• Inc. K excretion
• Inc. Mg excretion
• Dec. Ca urinary excretion
• Dec. peripheral vascular resistance

Adverse Effects:

• Hypokalemia
• Hyponatremia
• Metabolic alkalosis
• Hyperuricemia
• Hyperglycemia
• Hyperlipidemia
• Hypersensitivity
• Sexual dysfunction

Question 3

Spironolactone

Eplerenone

Answer 3

Class: K-sparing
Location: Collecting tubule

MOA:

• Antagonize aldosterone at intracellular cytoplasmic receptor
• Dec. Na reabsorption
• Dec. K excretion

Use(s):

• Heart failure (Spironolactone)
• HTN
• Primary hyperaldosteronism
• Edema

Action(s):

• Inc. Na excretion
• Inc. urine volume
• Dec. K excretion

Adverse Effect(s):

• Gastric upset
• Peptic ulcers
• Hyperkalemia
• Nausea
• Lethargy
• Mental confusion

Question 4

Amiloride

Triamterene

Answer 4

Class: K-sparing
Location: Collecting tubule

MOA:

• Block ENaC
• Dec. Na/K exchange
• Dec. Na reabsorption
• Dec. K excretion

Use(s):

• Heart failure
• HTN
• Primary hyperaldosteronism
• Edema

Action(s):

• Inc. Na excretion
• Inc. urine volume
• Dec. K excretion

Adverse Effect(s):

• Hyperkalemia
• Hyponatremia
• Leg cramps
• GI upset
• Dizziness
• Pruritus
• Headache
• Minor visual changes

Question 5

Acetazolamide

Answer 5

Class: CA inhibitor
Location: Proximal tubular epi. cells
Route: Oral, well absorbed
Acute: IV
t1/2 = 3-6h

MOA:

• Inhibit intracellular carbonic anhydrase
• Dec. ability to exchange Na for H
• Dec. activity of Na/K ATPase
• HCO3 is retained in lumen
• Inc. urinary pH

Use(s):

• Glaucoma
• Epilepsy
• Mountain sickness
• Metabolic alkalosis

Action(s):

• Inc. Na excretion
• Inc. K excretion
• Inc. HCO3 excretion
• Inc. urine volume

Adverse Effect(s):

• Metabolic acidosis
• Hyponatremia
• Hypokalemia
• Crystalluria
• Malaise
• Fatigue
• Drowsiness
• Depression
• Headache
• GI upset
• Paresthesia

Question 6

Mannitol

Answer 6

Class: Osmotic diuretic
Location: everywhere
Route: IV

MOA:

• Inc. osmotic pressure of plasma
• H2O from body
• Does not affect Na excretion directly
• Only drug that truly inc. urine volume

Use(s):

• Inc. urine flow, acute renal failure
• Dec. intracranial pressure
• Cerebral edema
• Inc. toxic substance excretion

Adverse Effect(s):

• Extracellular water expansion
• Tissue dehydration

Contraindication(s):

• Congestive heart failure
• Pulmonary edema

Question 7

Conivaptan

Answer 7

Class: ADH antagonist
Location: Collecting tubule
Route: IV

MOA:

• V1 & V2 antagonist
• V1 = inc. SM contraction
• V2 = inc. H2O permeability & reabsorption
• Metabolized & potent inhibitor of CYP3A4

Use(s):

• Euvolemic & hypervolemic hyponatremia
• SIADH
• Heart failure (benefits > risks)

Adverse Effect(s):

• Infusion site reactions
• Thirst
• Atrial fibrillation
• GI & electrolyte disturbances
• Nephrogenic diabetes insipidus

Contraindication(s):

• Hypovolemic hyponatremia
• Renal failure