Diuretics Flashcards
Where do Osmotic diuretic act
Proximal tubules, Loop of Henle, Collecting duct
Osmotic diuretics mechanism of action
They create an osmotic pressure which draws water from cells and the interstitium into the tubule lumen = Inhibition of water and Na+ reabsorption
Name some osmotic diuretics
Mannitol, isosorbide, glycerine and urea
Side effects of osmotic diuretics
CV toxicity immediately after injection, they can cause an increase in blood volume and so increases workload of the heart.
When not to use osmotic diuretics
If they have congestive heart failure
Carbonic anhydrase inhibitors site of action
Proximal tubules
Carbonic anhydrase inhibitors mechanism of action
Inhibition of bicarbonate reabsorption, preventing H+ formation and Na/H transported wont reabsorb any Na. They block the CA enzyme
Name some Carbonic anhydrase inhibitors
Acetazolamide, Methazolamide
When to use Carbonic anhydrase inhibitors
Raised intra-ocular pressure in open-angle glaucoma (they reduce aqueous humour secretion)
Ocular hypertension when monotherapy is inadequate
Side effects of Carbonic Anhydrase inhibitors
Metabolic acidosis
Renal stones (Calcium and phosphate)
Renal potassium wasting (enhanced K+ secretion due to NaHCO3)
When to use osmotic diuretics (Mannitol mainly)
1) it is inherently non-toxic,
2) it is freely filtered,
3) it is non-reabsorbable,
4) it is not metabolised,
5) the other agents may pass into cells to a limited extent.
Loop Diuretics site of action
Thick ascending limb of Loop of Henle
Loop Diuretics mechanism of action
Inhibit the Na+/K+/2Cl- co-transporter (NKCC2) in the thick ascending loop of Henle → decrease in Na+, K+ and Cl- reabsorption (blocks transport of NaCl out of the tubule into the interstitial tissue)
Name some Loop diuretics
Furosamide, Torasamide
When to use Loop diuretics
Treat water imbalances in Congestive HF, KF and pulmonary oedema
Loop diuretics contraindications
Don’t use if hypokalaemia
Don’t use with aminoglycoside antibiotics (e.g. Gentamicin) - cause HL and Kidney damage
NSAIDs reduce the effect of loop diuretics
Thiazide diuretics site of action
Early distal tubule
Thiazide diuretics mechanism of action
Block the thiazide-sensitive Na/Cl co-transporter - inhibit reabsorption of Na+ and Cl− from the distal convoluted tubules in the kidneys
Also increase Ca2+ reabsorption at distal tubules - lowering Na+ conc increases activity of Na/Ca co-transporter
Also cause a loss of K+
Thiazide diuretics contraindications
Hypotension
Gout (reduce clearance of uric acid)
Renal failure
Lithium therapy
Hypokalemia
May worsen diabetes
Name some thiazide diuretics
Hydrochlorothiazide, clorothiazide, bendroflumethiazide
Where do K+ sparing diuretics act
Late distal tubule
Collecting duct
K+ sparing diuretics side effects
Hyperkalaemia , so potassium supplements should not be co-prescribed.
Caution when used with drugs such as ACE inhibitors that increase blood potassium levels. Increases in K+ can lead to cardiac arrythmias
Aldosterone agonists (K+ sparing diuretics) mechanism of action
Aldosterone receptor antagonists reduce this expression of Na+/K+ATPase and ENaC thus reducing both Na+ reabsorption and K+ secretion
Name some Aldosterone agonists (K+ sparing diuretics)
Spironolactone, Eplerenone
Na+ channel inhibitors (K+ sparing diuretics) mechanism of action
Inhibit Na+ reabsorption by blocking ENaC on the apical membrane and reduce K+ secretion by a downstream reduction in Na+/K+ATPase activity on the basolateral membrane.
Name some Na+ channel inhibitors (K+ sparing diuretics)
Amiloride, triamterene
When to use K+ sparing diuretics
Used in combination with loop diuretics and thiazides to reduce K+ loss particularly where hypokalaemia is a concern.
What is Digoxin
An inhibitor of the Na+/K+ ATPase pump and binds to the alpha subunit that comes from Foxgloves
Digoxin mechanism of action
inhibits the Na+/K+ ATPase pump and binds to the alpha subunit.
This causes an increase in intracellular Na+.
This reduces the action of the Na+/Ca2+ exchanger in the resulting in increased intracellular Ca2+ which is then stored in the sarcoplasmic reticulum.
The Ca2+ is released during a cardiac action potential thus increasing the force of a contraction
When to not use Digoxin
Hypokalaemia resulting from loop diuretics and thiazides will potentiate the effect digoxin, thus increasing the risk of cardiac arrythmias
