S6) Diuretics Flashcards
What is diuresis?
Diuresis is the increased formation of urine by the kidney and the process of treating water from the kidney
What is a diuretic?
A diuretic is a substance/drug that promotes a diuresis by increasing the renal excretion of Na+/H2O, reducing ECF volume
When are diuretics used clinically?
Clinical use is in conditions where Na+ and H2O retention cause expansion of ECF volume and oedema eg. heart failure
→ reduce plasma volume and cardiac output
→ reduce blood pressure
→ reduce oedema
Briefly, describe how diuretics act on the nephron/kidney
Diuretics act by blocking reabsorption of Na+ and H2O by the tubule and increase the fractional excretion (FE) of Na+
→ remember that where na goes, Cl goes and h20 will too
Describe the 4 pathways in which diuretics can act on the nephron
- By blocking Na+ transporters in the luminal membrane
- By antagonising the action of aldosterone (promotes reabsorption of na into the blood)
- By modification of filtrate content (osmotic diuretics)
- By inhibiting activity of enzyme carbonic anhydrase in the PCT
Identify the 3 types of diuretics which act on cells to block Na+ transporters in the luminal membrane
- Thiazide diuretics
- Loop diuretics
- K+ sparing diuretics
Describe the action of loop diuretics
- Drug is secreted into the lumen in the PCT
- Acts on Loop of Henle
- Blocks NaKCC co-transporter
Describe the action of thiazide diuretics
- Drug is secreted into the lumen in the PCT
- Acts on the early Distal Tubule
- Blocks Na–Cl cotransporter
Describe the action of K+ sparing diuretics
- Drug is secreted into the lumen in the PCT
- Acts on Late DT & CD
- Blocks Epithelial Na channels (ENaC)
Describe how aldosterone acts on the kidney nephron
Aldosterone acts on principal cells of Late DT & CD to increase Na+ reabsorption via ENaC
Identify and describe the mechanism of action of diuretics which antagonise the action of aldosterone
- Aldosterone antagonists act through competitive inhibition of the aldosterone receptor, decreasing Na+ reabsorption
- They also have a K+ sparing effect
Osmotic diuretics act by modifying the filtrate content.
Describe this
Small molecules are freely filtered at glomerulus but not reabsorbed:
- Increased osmolarity of filtrate
- Reduced water & Na+ reabsorption throughout the tubule
Describe the action of carbonic anhydrase inhibitors
Carbonic anhydrase has an inhibiting effect and interferes with Na+ & HCO3- reabsorption in PCT
Loop diuretics block apical Na-K-2 Cl transporter.
In 5 steps, explain how this leads to diuresis
⇒ Na+ and Cl- is not absorbed resulting in less H2O absorption
⇒ Result is: Na+ and H2O loss
⇒ K+ carried across apical membrane drifts back into lumen via K+ channels
⇒ Creates a (+) lumen potential
⇒ This decreases the absorption of Ca2+ and Mg2+
Provide 2 examples of loop diuretics
- Furosemide
- Bumetanide
Loop diuretics are very potent.
What is the impact of this?
- Affects 25 - 30% of filtered sodium reabsorption
- Segments beyond have limited capacity to reabsorb the resulting flood of Na+ & H2O
Describe the use of loop diuretics in heart failure
- Treats of symptoms of breathlessness & oedema
- Causes vaso and venodilatation (decreases after/preload)
- No effect on reducing mortality
Describe the use of loop diuretics in treating acute pulmonary oedema
IV Furosemide given for rapid action
Loop diuretics are used to treat fluid retention & oedema in a number of clinical conditions.
Identify 3
- Nephrotic syndrome
- Renal failure
- Cirrhosis of liver (spironolactone preferred)
Loop diuretics are also used in treatment of hypercalcaemia.
Explain the benefit of this
- Impairs calcium absorption in the Loop of Henle
- Increases urinary excretion of calcium
- Furosemide given together with IV fluids
Thiazide diuretics block Na–Cl transporter in DCT.
In 4 steps, explain how this leads to diuresis
⇒ Diuretic secreted into lumen in PCT and travels to act on DCT
⇒ Blocks Na+ absorption and increases Ca2+ absorption
⇒ Increases Na+ (and H2O) loss in urine
⇒ Reduces Ca2+ loss in urine so reabsorb more Ca
Provide an example of a thiazide diuretic
Bendroflumethiazide
indapamide
Thiazide diuretics are less potent diuretics than loop diuretics.
How does this manifest?
- Only 5% of sodium reabsorption inhibited
- Ineffective in renal failure
Where are thiazide diuretics most commonly used?
Widely used in hypertension (vasodilatation)
first line antihypertensive drug
Two groups of drugs have potassium sparing diuretics.
Identify these groups and provide examples
Act on late distal tubule and collecting duct:
- Inhibitors of ENaC e.g. Amiloride, triamterene
- Aldosterone antagonist e.g. Spironolactone