Diuretics Flashcards
What are the different parts of the nephron?
- Bowmans Capsule
- Proximal convoluted tubule (PCT)
- Distal convoluted tubule (DCT)
- Thin descending limb
- Loop of Henle
- Thin ascending limb
- Thick ascending limb
- Collecting duct
What are the types of diuretics that occur in the nephron?
- Osmotic diuretics
- Loop diuretics
- Carbonic Anhydrase Inhibitors
- Thiazides
- Aldosterone antagonists
What do diuretics interfere with?
Ionic transport in the nephron to decrease tubular reabsorption
How do diuretics work?
Act at different sites of the nephron causing Natriuresis (increase in Na+ excretion) which leads to diuresis (increase in urine volume)
What is a diuretic?
Something that will increase the production of urine
Why are diuretics useful?
Useful in the treatment of hypertension or oedema associated with congestive heart failure
- reduce blood pressure
- reduce oedema
What are osmotic diuretics?
Drugs that alter the osmolality of the plasma, since very little drug is reabsorbed or metabolised so water follows the concentration gradient where more water is retained in the PCT and descending limb resulting in increased urinary output via osmosis
What is an example of osmotic diuretics?
Mannitol
- Increases osmolality of tubular fluid at PCT
- Increases urinary output (diuresis)
What are carbonis anhydrase inhibitors?
An enzyme that facilitates the exchange for H+ from Na+ and water in the proximal tubules
-Block this exchange of ions, thereby reducing the H+ concentration in the renal tubules (result is increased excretion of HCO3- , Na+ , K+ and Water
What are carbonic anhydrase inhibitors used to treat?
Glaucoma, Oedema (secondary to heart failure), high altitude sickness and epilepsy
What is an example of Carbonic Anhydrase inhibitors?
Acetazolamide
-Inhibit reabsorption of bicarbonate (HCO3-), a process normally driven by carbonic anhydrase
Has limited effectiveness:
- Increased Na+ and Cl- reabsorption in DCT
- Associated with metabolic acidosis
- Weak diuretic
What are loop diuretics?
Drugs that prevent the creation of a hypotonic interstitium in the medulla by acting on the ascending limb of the loop of henle to block the Na+/K+/2Cl- symporter
- Increase Na+ delivery to DCT (promotes K+ loss)
- Decrease Na+ entry into macula densa (promote renin release and therefore increased angiotensin II activity)
How effective are loop diuretics?
Sometimes referred to as ‘high ceiling’ diuretics due to their potent diuretic effects - can cause 15-25% of filtered Na+ to be excreted
What are loop diuretics used to treat?
Pulmonary oedema (secondary to left ventricular failure and chronic heart failure)
What is an example of Loop Diuretics?
Furosemide
- Solute added to peritubular fluid (water not reabsorbed)
- Act on thick ascending limb of loop of henle by blocking Na+/K+/2Cl- symporter
What are Thiazides?
Third line drugs in hypertension
-Block Na+ and Cl- reabsorption in the DCT
What are the used of thiazides?
- Used as a third line treatment for hypertension in patients over 55years old
- Secondary use is mild to moderate heart failure (particularly in the elderly)
- Ineffective in moderate renal impairment as the thiazides can’t go into the tubular system
What example is there for Thiazides?
Bendroflumethiazide
- Moderately powerful diuretics
- Act on DCT to inhibit active Na+ reabsorption
- Increase solute in tubular fluid and decrease water reabsorption
- Reduce circulating volume
Uses: -Hypertension
-Mild to moderate heart failure
What are K+ sparing diuretics?
- Block actions of aldosterone and/or block Na+ channels
- Help overcome the hypokalemic action of diuretics (which can develop in cardiac arrhythmia)
When and why are K+ sparing diuretics used?
Used in conjunction with other diuretics
-Help maintain K+ balance in the body
May be used in the treatment of hyperaldosteronism, hypertension and heart failure
What are the examples of K+ sparing diuretics?
Spironolactone
- Acts as aldosterone antagonist in the late DCT
- Blocks the action of aldosterone which would otherwise cause Na+ reabsorption and K+ and H+ secretion
- Prevents hypokalaemia caused by renal loss of K+ ions
- Secondary effect of several diuretics, including carbonic anhydrase inhibitors, loop diuretics and thiazides
How do the electrolyte changes in in urine differ based on the administration of each diuretic drug?
Carbonic Anhydrase Inhibitors: Small increase in Na+
Small increase in K+
Large increase in HCO3-
Loop Diuretics:
Large increase in Na+
No change in HCO3-
Small increase in K+
Thiazides:
Medium increase in Na+
Small increase in K+
No increase in HCO3-
K+ sparing diuretics:
Small increase in Na+
No change in HCO3-
Small decrease in K+
