Diuretic Drugs

Question 1

Osmotic diuretics

Answer 1

Large molecules that can get into the renal tubule - hold water in and promote increase in urine volume and inhibits solute reabsorption by virtue of its effects on counter current mechanisms

• site of action - proximal tubule and loop of henle
• effects - initial expansion of intravascular fluid volume, increased renal blood flow; then increased excretion of urinary electrolytes (isosmotic water loss);
• good use to maintain diuretic effect during hypovolemia or shock (during trauma situations)

Question 2

Mannitol

Answer 2

• preferred osmotic diuretic
• administered parenterally
• promotes excretion of certain toxins
• bad to use with congestive HF because the first osmotic effect you see is an increase in intravascular volume
• don’t use in anuric renal failure that does not respond to a test dose

Question 3

Glycerol

Answer 3

• osmotic diuretic
• can be given orally
• used for the treatment of glaucoma
• contraindications - diabetes mellitis becuase glycerol increases glucose levels and can make the animal hyperglycemic

Question 4

NaCl

Answer 4

• Osmotic diuretic
• increases water consumption - can be used to dilute urine
• helps diluting stone formation substances

Question 5

Ammonium chloride

Answer 5

• Osmotic diuretic
• given orally
• main use is a urinary acidifier
• can create subclinical metabolic acidosis - don’t use in patients with systemic acidemia

Question 6

Carbonic Anhydrase Inhibitors

Answer 6

• Site/mechanism of action - proximal tubule (inhibit carbonic anhydrase)
  
  • Decrease H+ secretion, decreases Na+ and HCO3- reabsorption
  • Minor effects at collecting duct - more Na+ in lumenal fluid, more Na+ exchanged for K+ - increased K+ secretion (indirect effect)
• Effects - increased excretion of HCO3-, Na+ and K+ and water
  
  • Metabolic acidosis and decreased excretion of ammonia
  • Decreased prodcution of aqueous humor (helps in animals with glaucoma)
  • Normally, carbonic anhydrase is an enzyme responsible for the formation of carbonic acid à carbonic acid dissociates to bicarb which is reabsorbed back into the blood stream and H+ ion which is secreted into the tubular lumen and participates in sodium reabsorption (H+ is exchanged for Na+). If you block carbonic anhydrase, less hydrogen ion is available for exchange with sodium, causing more sodium to be excreted. You will also have less bicarb reabsorbed because there is less available.

Question 7

Methazolamide

Answer 7

• Carbonic Anhydrase Inhibitor
• Major use for treatment of glaucoma
• Can be used to produce alkaline urine (transient effect)
• Extralabel use - treating udder edema
• Contraindications:
  
  • Related to sulfas - potential allergies
  • History of renal or urinary calculi that form in alkaline urine
  • Presence of metabolic or respiratory acidosis

Question 8

Loop Diuretics

Answer 8

• “high ceiling diuretics” - profound diuresis
• Most commonly used diuretic in vet med; actively secreted into proximal tubule
• Most effective diuretic for treating any non-inflammatory edematous condition
• Site of action - thick ascending limb of loop of henle
• Mechanism - inhibit Na+/K+/2Cl symport; inhibit paracellular diffusion of Na, K, Mg, and Ca (decreased electrical gradient)
• Effects:
  
  • Profound increase in Na excretion (also increased excretion of Cl, water, K+, H+, Ca2+, and Mg2+
  • Mild systemic venodilator (acutely increases renal blood flow)
  • Increased renin secretion due to decreased Na+ levels in plasma
  • May cause metabolic acidosis

Question 9

Furosemide

Answer 9

• Preferred loop diuretic
• Very short acting
• Use in congestive heart failure to treat noninflammatory edema
• Use in hypercalcemia
• Prophylaxis for epistaxis (nosebleed) in equine
• Only diuretic with significant effect in patients with impaired renal function

Question 10

Bumetanide and Toremide are what kind of diuretics?

Answer 10

Loop diuretics

Question 11

Thiazide Diuretics

Answer 11

• “Rescue Diuretics”
  
  • Work at the distal tubule to block Na/Cl symport - decreases Na+ reabosrption
  • Works at the early distal tubule BEFORE the site for Na/K exchange
• Characteristics
  
  • Secreted into proximal tubule
  • Decreased Na+ reabsorption and increased K+ secretion (increased Na+ load in tubular fluid promotes Na/K exchange)
• Effects:
  
  • Mild diuresis; rarely used as first choice diuretic
  • Increased excretion of Na+, Cl- and K+
  • Decreased excretion of Ca2+

Question 12

Hydrochlorothiazide

Answer 12

• Preferred thiazide diuretic (longer duration - 12 hours)
• Used in refractory heart failure - when resistance to furosemaides develops
  
  • Has diuretic effect on its own but also restores diuresis in response to furosemide
• Help streat ascites due oto liver disease
• Treatment for diabetes insipids - paradoxically decreases urine flow in these patients (patients with diabetes insipidus are deficient in ADH, resulting in high isosmotic urine flow and the lower collecting duct is not permeable to water, so the patient loses water and electrolytes in the urine)
• Contraindications:
  
  • don’t use if animal is hypokalmic
  • don’t use in diabetes mellitus

Question 13

K+ sparing agents

Answer 13

• Diuretic that can cause diuresis but you don’t lose potassium
• Act at the late distal tubule and at the early collecting duct
  
  • Two different types:
    
    • Antagonize aldo (spironalactone) - blocks Na/K exchange
    • Block sodium channels (triameterine) in tubular cells of the late distal tubule and collecting duct
• Main effect is to increase excretion of NaCl but decrease excretion of K+ and other cations
• Actively secreted by the renal tubules

Question 14

Spironolactone

Answer 14

• K+ sparing agent - antagonize aldosterone by blocking active Na/K exchange
• Used in refractory heart failure - mainly used in combination with other diuretics (furosamide)
• Used with ACE inhibitors - be aware of risk of hyperkalemia (because both are K+ sparing) unless furosemide is also given
• Contraindications:
  
  • Hyperkalemia
  • Use caution when administering with other drugs that increase blood K+ like ACE inhibitors and NSAIDs

Question 15

Triamterene

Answer 15

• Potassium sparing agent - blocks sodium channels in tubular cells of hte late distal tubule and collecting duct
• Used infrequently in vet med