Drugs acting on the kidneys 1 Flashcards
Define in general terms what a diuretic is
Agents that increase urine output through causing a net electrolyte (mainly sodium) and water loss.
How do diuretics enter the glomerular filtrate to have there effect ?
- Glomerular filtration
- Secretion via transport process in the proximal tubule
What diuretics are secreted into the tubule via The organic anion transporters (OATs)?
Loop and thiazide diuretics
What diuretics are secreted into the tubule via The organic cation transporters (OCTs)?
Triamterene and amiloride
Where in the glomerulus and on what does loop diuretics act ?
Inhibits the Na+/K+/2Cl- cotransporter in the thick ascending loop of henle by binding to Cl- site in the transporter
Describe the mechanism of action of loop diuretics
- Acts on Na+/K+/2Cl- cotransporter, preventing the transporter from being able to reabsorb Cl-
- This then prevents the transporter from working correctly so Na+ and K+ are then also not reabsorbed
- In the long-term Ca2+ and Mg2+ are also not reabsorbed
Increased Na+, H20, Cl-, K+, Ca2+ and Mg2+ excretion
What is the secondary affect of loop diuretics ?
They have a secondary venodilator action which is beneficial in pulmonary oedema caused by HF
Give some examples of loop directics and how you remember them
- Furosemide and Bumetanide
- Think ‘mide and nide’
What is the typical responsiveness of patients to furosemide and what affects it?
Responsiveness to furosemide is very variable from 20-100% and depends on drugs, liver function (approx. 50% is metabolised by the liver) and amount of bile salts
What are the clinical uses of loop diuretics ?
- Acute pulmonary oedema
- Chronic HF
- Chronic KD
- Nephrotic syndrome
- Hepatic cirrhosis with ascites
- Acute kidney failure
- Hypercalcaemia and stones
What is the equivalent doses of furosemide to bumetanide ?
1mg of bumetanide is equivalent to 40mg of furosemide
What is the action of thiazide diuretics and where in the glomerulus does this occur ?
Inhibit the Na+/Cl- symporter in the distal tubule ==> inhibiting Na+ reabsorption
Describe the mechanism of action of thiazide diuretics
- Inhibit the Na+/Cl- symporter in the distal tubule, and since H20 follows salt then water is excreted also
- In the long-term there is increased Ca2+ reabsorption and Mg2+ secretion (excretion)
There is increased Na+, K+, Cl- and H20 excretion
Increased Ca2+ reabsorption
Increased Mg2+ secretion (excretion)
Why is there still increased K+ loss with thiazide diuretics when they do not act directly on a transporter involving K+ ?
This is because as they act on the Na+/Cl- transporter in the distal convoluted tubule ==> this results in increased levels of Na+ in the distal part of the tubule (as more Na+ is getting excreted) which in turn the increased conc. of Na+ stimulates the aldosterone sensitive Na+ pump in the distal part of the tubule to reabsorb Na+ in exchange for K+ and H+ ions ==> this is also therefore the mechanism by which it can cause metabolic alkalosis.
What are the clinical uses of thiazide diuretics ?
Widely used in mild HF and hypertension
What is the secondary action of thiazide diuretics?
Vasodilator action that contributes to there effectiveness in treatment of hypertension
Which diuretic is still effective in patients with severe renal failure ?
Loop diuretics (thiazide are not)
Give some examples of thiazide diuretics and the way to remember them
- Bendroflumethazide
- Think ‘thiazide’
How do loop and thiazide diuretics cause hypokalaemia ?
- They increase Na+ load in filtrate
- This causes increased reabsorption of Na+ in the late distal tubule and collecting ducts (through activation of aldosterone sensitive sodium pump)
- This leads to enhanced secretion of K+ and H+ due to low Na+ stimulating RAAS
Note that loop diuretics will also be directly resulting in loss of K+ through inhibition of the triple co-transporter (also the loss in their Cl- ions also due to an inverse relationship with HCO3- bicarb will mean bicarb will increase which is why loop diuretics can also cause metabolic alkalosis)
What are the signs of hypokalaemia ?
- Weakness/fatigue
- Myalgia
- Arrhythmias
What is done to prevent hypokalaemia in patients on diuretics ?
- Potassium supplements
- Use of potassium sparing diuretics e.g. spironolactone
Give a rough overview of the doses if furosemide and when you would switch to IV furosemide and further then IV to an infusion.
