Diuretics Flashcards
What is primarily reabsorbed in the proximal tubule and what percentage of the filtered load is this?
Na and Cl
50-70% of filtered load
What two elements are secondarily re-absorbed in the proximal tubule?
K+ and HCO3
What percent of Na and Cl is reabsorbed in the Ascending loop of Henle? By what type of absorption?
20-30%
Active chloride reabsorption
Is any water reabsorbed in the ascending loop?
NO
What mechanism is present in the ascending loop to compensate for increased Na intake?
Active absorption can adjust reabsorption
How much Na is reabsorbed in the distal tubule and collecting duct?
8-9%
What action does the distal tubule and collecting duct have on potassium movement?
Potassium is secreted into the tubule
What substance regulates sodium and potassium exchange in the distal tubule?
Aldosterone
What regulates water permeability in the distal tubule/collecting duct?
ADH
What drugs are considered renal vasodilators that subsequently have a diuretic effect?
Dopamine
Fenoldapam
Caffeine
Atriopeptins
What is the mechanism of action for renal vasodilator medications? (4 items)
They increase renal blood flow without changing the GFR
This decreases FF which is GFR/RBF
This then decreases proximal tubular sodium reabsorption
Compensation by distal nephron limits diuretic effects
How does a decreased filtration fraction decrease proximal tubular reabsortion?
There is a higher peritubular capillary hydrostatic pressure and decreased peritubular capillary oncotic pressure. This decreases the amount of fluid passively reabsorbed and increases the amount of fluid that is leaked from peritubular capillaries into the proximal tubule
What is the prototype osmotic diuretic for this course?
Mannitol
What are the three major characteristics of osmotic diuretics?
- Freely filtered
- Not reabsorbed
- Metabolically inert
What is the site of action and mechanism of action for osmotic diuretics? (3 items)
- Acts in tubular lumen as non-reabsorbable solute
- Urine volume and sodium excretion are proportional to the osmotic load
- Increases the urinary excretion of sodium, potassium, chloride, water and mannitol
What are the therapeutic uses for osmotic diuretics like Mannitol? (3 items)
Edema
Glaucoma
Acute renal failure
What is the prototype medication for carbonic anhydrase inhibitors?
Acetazolamide
What are the three main characteristics of Acetazolamide?
- Orally active
- Weak diuretics
- Inhibited by acidosis which limits clinical use
What is the site of action for carbonic anhydrase inhibitors like Acetazolamide?
Proximal and distal tubule
What is the mechanism of action for carbonic anhydrase inhibitors like Acetazolamide? (4 items)
- Inhibits carbonic anhydrase in the proximal and distal tubule
- This limits hydrogen ions available for bicarbonate reabsorption
- This increases sodium, potassium, bicarb, and water excretion
- This creates an alkalinization
What are the side effects of carbonic anhydrase inhibitors like Acetazolamide? (2 items)
- Metabolic acidosis
2. Hypokalemia
What are the therapeutic uses for carbonic anhydrase inhibitors like Acetazolamide? (4 items)
- Glaucoma (reduced aqueous humor formation)
- Alkalinize the urine (decrease drug toxicity)
- Mountain or altitude sickness
- Anticonvulsant
What are the prototype loop diuretics for this course? (3 items)
- Furosemide
- Bumetanide
- Ethacrynic Acid
What are the 4 major characteristics for loop diuretics for this course?
- PO or IV admin
- High efficacy/Strong diuresis (20-30% filtered Na load)
- Rapid onset (20-30 min)
- Short duration of action
Where is the site of action for loop diuretics?
Cortical and Medullary segments of the ascending limb of loop of henle
What is the mechanism of action of furosemide or bumetanide?
- Inhibits the Na-K-2Cl symporter in ascending loop
2. Increases the excretion of sodium, potassium, chloride and water
What secondary effects do furosemide and bumetanide (loop diuretics) have? (2 items)
- Increases renal blood flow & GFR
2. Enhances calcium excretion
What are the side effects/disadvantages of loop diuretics?
- Hypokalemia
- Alkalosis
- Hypovolemia
- Hyperuricemia (increased urate reabsorption in PT)
- Hyperglycemia (furosemide only)
- Ototoxicity
What are the therapeutic uses/clinical indications for loop diuretics like furosemide and bumetanide?
- Edema of cardiac, hepatic, or renal origin
- Acute pulmonary edema
- Hypertension
What are the prototype medications for the Thiazide diuretic class?
- HCTZ
2. Metolazone
What are the 4 major characteristics of thiazide diuretics?
- Orally active
- Intermediate efficacy (8-10% of filtered load)
- Moderate onset of activity (60 min)
- Long duration of action
What is the site of action of thiazide diuretics?
Distal tubule
What is the mechanism of action for thiazide diuretics like HCTZ and Metolazone?
- Inhibits Na-Cl symporter
- Acts on cortical segment of distal tubule
- Increases excretion of sodium, potassium, chloride and water
- Urine becomes hypertonic
What are the secondary actions of HCTZ and Metolazone (thiazide diuretics)? (2 items)
- Increases potassium secretion
2. Enhances urate reabsorption (PT)
What are the disadvantages/side effects of thiazide diuretics like HCTZ and Metolazone? (5 items)
- Hypokalemia
- Alkalosis
- Hyperuricemia
- Hyperglycemia
- Decrease in GFR with thiazides
What are the therapeutic uses/clinical indications for HCTZ and Metolazone (thiazide diuretics)? (3 items)
- Edema due to CHF
- Hypertension
- Hypercalciuria/Ca salt - renal caliculi
What are the two types of K+ sparing diuretics?
- Aldosterone Antagonists
2. Sodium channel inhibitors
What are the two examples of Aldosterone antagonists?
- Spironolactone
2. Eplerenone
What are the two examples of sodium channel inhibitors?
- Amiloride
2. Triamterene
What are the 4 major characteristics of potassium sparing diuretics?
- Orally active
- Low efficacy (2-3% filtered Na load excreted)
- Increases Na excretion without K loss
What is the site of action for potassium sparing diuretics?
cortical collecting tubule
What is the mechanism of action for aldosterone antagonists like Spironolactone or Eplerenone?
Blocks the action of aldosterone on the collecting duct increasing sodium excretion and reducing potassium excretion.
What is the mechanism of action for sodium channel inhibitors like Amiloride or Triamterene?
Blocks sodium entry into principal cells of the collecting duct. This increases sodium and water excretion.
What are the disadvantages/ side effects of potassium sparing diuretics? (5 items)
- Low efficacy
- Hyperkalemia
- Gynecomastia with Aldosterone inhibitors (spironolactone is the worst)
- Triamterene decreases RBF and GFR at high doses
- Na channel inhibitors create mild azotemia
What are the therapeutic uses/clinical indications for potassium sparing diuretics? (4 items)
- Edema
- Hypertension
- Combination therapy for enhanced diuresis without K+ loss.
- Aldosterone antagonists improve survival in heart failure.
What is the order of intrinsic activity with different classes of diuretics?
Loop > Thiazides > K+ sparing
What is the order of least to most expensive in classes of diuretics?
Thiazides < Loop < K+ sparing
Which has a faster onset of action, Loops or Thiazides?
Loop
What is the ceiling effect of diuresis?
The amount of effective diuresis is limited by the total percent excretion of sodium. Additional attempts to diurese beyond this ceiling will only result in damage and not therapy.
What type of diuretic is best for vascular fluid overload or ECF edema like pulmonary edema or peripheral edema?
Fast acting strong diuretic
What type of diuretic is best for body compartment fluid overload like acites? Why?
Slow acting with long duration. Protect against overdiuresis of vascular and ECF compartments as fluid transfer from body compartments to ECF compartments is very slow.
What is the foundation for diuresis with anti-hypertensive therapy?
- Lowers blood pressure on its own
2. Prevents compensatory salt and water retention
What are the mechanisms for vasodilation by diuretics? (5 items)
- Decreased Na/water in vessel wall
- PGI2 and NO release
- Vascular K channel activations
- Decreased sensitivity to NE
- Increased Na-Ca exchange
Which diuretic is associated with a reduction in mortality in heart failure?
Spironolacton or Eplerenone
What contribution do furosemide and HCTZ have in CHF?
- reduce fluid volume and preload
- reduce heart size
- reduce edema
- Not associated with reduction
Why does Spironolactone or Eplerenone reduce risk of mortality with CHF?
It blocks the effects of aldosterone on the heart which decreases fibrosis and hypertrophy and arrhythmias.