Diuretics Flashcards
What are 5 classes of diuretic? [5]
Carbonic anhydrase inhibitors
Thiazide
Loop
Potassium sparing diuretics
Osmotic diuretics
Where do carbonic anhydrase inhibitors work? [1]
MoA of CA inhibitors?
- CA inhibitors work at PCT
- Causes more HCO3-, H+ & Cl- excreted in urine
- Get less CO2 and water in cell
Which of the following is the most effective type of diuretic?
Carbonic anhydrase inhibitors
Thiazide
Loop
Potassium sparing diuretics
Osmotic diuretics
Which of the following is the most effective type of diuretic?
Carbonic anhydrase inhibitors
Thiazide
Loop: e.g. Frusemide
Potassium sparing diuretics
Osmotic diuretics
Where do loop diuretics work? [1]
How do they work? [1]
Loop diuretic: work at thick ascending limb
MoA:
- Block NaKCl2 transporter (competing with Cl- for binding site)
- Less Na into tubular cell: less Na into blood / more Na excreted in urine
- Results in less K+ reabsorbed
- Causes decreased Ca2+, Mg2+ absorption via paracellular transport
Explain two AEs of using loop diuretics? [3]
Hypokalemia: directly blocks K reabsorption through blockage of NaKCl2
Dehydration
Kidney stones: due to retained Ca in urine
Deafness
Thiazide diuretics work in which location of nephron? [1]
MoA of thiazide diuretics? [1]
Thiazide diuretics: work at DCT
MoA: Blocks Na/Cl transporter
Explain how thiazide diuretics impact K+ levels
Cause hypokalaemia:
- Thiazied diuretics block Na/Cl transporter at DCT
- Na is delivered to CD, where absorbed by ENaC channels
- This causes the aldosterone-sensitive Na/K pump to increase Na reabsorption in the principal cells
- This exchange increases Na transfer into the interstitium and increases K transfer into the collecting tubules and lumen.
What are the two type of K sparing diuretics? [2]
Name two examples of each xx [4]
Epithelial Na Channel antagonists
* Amiloride
* Triamterene
Aldosterone antagonists:
* Spironolactone
* Eplerenone
Where do potassium sparing diuretics, such as spironolactone or eplerenonework in nephron? [1]
MoA? [1]
How do they ensure K+ reabsorption? [1]
Spironolactone and eplerenone work at CD
Both: aldosterone antagonists (Na/K transporter)
Because Na doesn’t get reabsorbed into blood, K doesn’t have to be excreted in exchange
Where do Epithelial Na Channel antagonists
potassium sparing diuretics, like Amiloride or Triamterene work in the nephron? [1]
MoA? [1]
How do they ensure K+ reabsorption? [1]
Collecing Duct / Distal tubule
Work by blocking urine lumen side Na+ transporter: stops Na+ reabsorption; driving force for K+ secretion is eliminated
What is a osmotic diuretic and which is the most clinically important? [2]
Any osmotically active molecule that is freely filtered in the glomerulus, and is not reabsorbed by the tubules, stopping water reabsorption
Most important clinical osmotic diuretic: Mannitol
What is Acetazolamide mainly used for? [1]
Mountain sickness: try and reverse resp. alkalosis by creating metabolic acidosis (by increasing HCO3- excretion)
What are AEs of CA inhibitors like Acetazolamide? [3]
Metabolic acidosis
Sedation
Sulphonamide antibiotics
What is clinical use of thiazide diuretic? [1]
Why? [2]
Antihypertensive:
reduces plasma volume and peripheral resistance
AEs of thiazide diuretics? [3]
Hypokalaemia: K+excretion is enhanced due to the increase in Na+delivered to the distal tubule.
Hypercalcaemia: Ca2+excretion is decreased via a poorly understood mechanism
Hyponatraemia (particularly in old people)
Explain AEs of thiazide diuretics? [5]
Hypokalaemia: K+excretion is enhanced due to the increase in Na+delivered to the distal tubule / CD, where Na is reabsorped at expense of K+
Hypercalcaemia: Ca2+excretion is decreased via a poorly understood mechanism
Hyponatraemia (particularly in old people)
Hyperglycaemia: inhibits insulin secretion slightly
Hypercholesterolaemia: unknown mech
Thiazide diuretics cause increase excretion of which electrolytes? [2]
K+, Na+
Clinical use of loop diuretics? [3]
- Most potent diuretic
Also for:
* HTN
* Heart failure
* Volume overload from CKD
Loop diuretics cause increase excretion of which electrolytes? [4]
K+, Na+, H20, Ca, Mg.
Explain how loop diuretics maintain renal blood flow
.Loop diuretics block the Na+, K+, Cl-symporter in the macula densa.
As a result the tubuloglomerular feedback mechanism is blocked
. Because of this loop diuretics maintain renal blood flow.
Why can loop diuretics cause kidney stones?
Loop diuretics cause increase Ca2+ excretion: increases chances
What are clinical uses of aldosterone inhibitors? [4]
Hyperaldosteronism (Conns)
Heart failure
Hypokalaemia (from other diuretics)
Cirrhosis
AEs of aldosterone inhibitors? [3]
Hyperkalaemia
Hyperkalaemia –> can lead to cardiac arrythmias and death
Hyperkalaemia
Gynecomastia (not eplerenone)
Hyponatraemia (Cirrhosis)
Why do aldosterone inhibitors lead to hyperkalaemia?
Na not excreted, so K kept
Clinical uses of amiloride?
Heart failure
Hypokalaemia (from other diuretics)
Co-amilofruse
Co-amilozide
Cirrhosis
AEs of amoliride? [2]
Hyperkalaemia
Hyponatraemia
When would you use osmotic diuretic clinically? [1]
Clinical use:
* Cerebral odema
AEs:
* Transient fluid overload: pulmonary odema
* If using glucose: DKA/HHS
* If using urea: Disequilibrium syndrome
When should you not use diuretics ! [5] key
When hypotensive
When dehydrated
When hypokalaemic (Loop/Thiazide)
When hyperkalaemic (Amiloride, aldosterone antagonists)
Post surgery, with a poor urine output
Explain MoA of SGLT-2 inhibitors
Normally SGLT2 allows Na AND glucose to be reabsorbed at PCT
Blocking SGLT2 causes more Na to be delivered to macula densa: here it causes glomerulus afferent arteriole constriction, which normalises GFR. Also causes glucose to be excreted in urine
Effects of SGLT2 inhibitors? [5]
Glycosuria: weight loss, reduction in blood glucose, HbA1c reduced
Uric acid reduced
Natuiresis: fall in BP
Reduced hyperinfiltration: reduced albuininuria
Reversible reduction in GFR
Cardio protective effects of SGLT-2 inhibitors?
