Lecture 5 - Diuretics Flashcards
What is the function of diuretics?
Increase production of urine to eliminate water from the body
What is the purpose of diuretics removing excess water from the body?
Reducing plasma volume + cardiac output
Reduce BP
Reduce oedema/Ascites
What are drugs called that increase excretion of sodium and water resulting in increased urine volume?
Diuretics
What is Diuresis?
Excretion of water in urine
What is natriuresis?
Excretion of sodium in the urine
What are the 5 classes of diuretics?
Carbonic anhydrase inhibitors
Osmotic diuretics
LOOP DIURETICS
POTASSIUM SPARING DIURETICS
THIAZIDE AND THIAZIDE-LIKE DIURETICS
What is the main ion which most diuretics interfere witht the normal reabsorption of?
What diuretic doesn’t do this?
Na+
Osmotic diuretics
What part of the nephron do carbonic anhydrase inhibitor diuretics work on?
PCT
What part of the nephron do osmotic diuretics work on?
Whole nephron (most effect at PCT)
What part of the nephron do Loop Diuretics work on?
Loop of Henle
What part of the nephron do Thiazide and thiazide like diuretics work on?
DCT
What part of the Nephron do potassium sparing diuretics work on?
DCT and Collecting Duct
How do carbonic anhydrase inhibitors act as diuretics?
Inhibit carbonic anhydrase
Less carbonic acid broken down into H20 and CO2
Less CO2 diffuses into PCT cell
Less H2CO3 made from CO2 + H20 so less HCO3- and H+ made
Since theres less H+ in the PCT cell the Na+/H+ exchanger works less so less Na+ reabsorbed into the PCT cell (more lost in urine)
What are Flozins?
How are they similar to a diuretic but aren’t a diuretic?
Inhibit SGLT-2 reducing the absorption of Na+ since less glucose being reabsorbed
(Less Na+ reabsorbed = less water reabsorbed)
What is an example of an osmotic diuretic?
Mannitol
How do osmotic diuretics work?
Increase water excretion by acting as an osmole drawing and keeping water in nephron
Why are osmotic diuretics not used in patients with heart failure and pulmonary oedema?
It expands the extracellular fluid volume initially as it travels to the kidneys
When are osmotic diuretics used?
Acute renal failure due to shock or trauma (increase extracellular fluid volume)
Acute drug poisoning (elimates drugs reabsorbed from renal tubules)
Decreases intracranial and Intra ocular pressure before surgery
How can using osmotic diuretics lead to hyponatraemia and hypernatraemia at different stages?
Initially causes hyponatraemia due to extracellular fluid expansion
Then excess use leads to dehydration and hypernatraemia
What channels do Loop diuretics block in the loop of Henle?
NKCC channels
How does loop diuretics block NKCC channels in the LOH lead to a diuretic affect?
Less Na+, K+ and 2Cl- reabsorbed into the cell so more stays in the LOH lumen
Water stays with the ions
What other affect can loop diuretics have on the body?
Hypocalcaemia
Hypomagneseamia
How can loop diuretics cause hypomagnesaemia and Hypocalcaemia?
The NKCC channel gets blocked means less Na+, Cl- and K+ reabsorbed, this means less K+ leak back across into the lumen via ROMK so the lumen doesn’t become positively charged
This means theres less repelling force so less Mg2+ and Ca2+ reabsorbed via paracellular transport
What is the most potent type of diuretic and why?
Loop Diuretics
They block NKCC channels which maintains the osmotic gradient
What are some loop diuretics?
Furosemide
When are loop diuretics used?
Severe oedema from congestive heart failure
Treating Hypercalcaemia
Acute pulmonary oedema
Acute Hyperkalaemia or acute Hypercalcaemia
How can loop diuretics lead to metabolic alkalosis?
Loss of water leads to increased concentration of bicarbonate ions in blood making it more alkaline
What are some side effects of loop diuretics?
Hypovolaemia
Hyponatraemia
Hypokalaemia
Hypomagnesaemia
Hypocalcaemia
Metabolic alkalosis
Postural hypotension
What channel do Thiazide and Thiazide like diuretics block?
Na+/Cl- cotransporter in the DCT
How does Thiazide/Thiazide like diuretics cause a diuretic effect?
Blockage of the Na+/Cl- cotransporter means less Na+ reabsorbed into DCT cell so less Na+ reabsorbed into vasa recta
Less Na+ in vasa recta means less water follows it into the vasa recta
How can thiazide lead to Hypercalcaemia?
Blocks the Na+/Cl- cotransporter of the DCT cell
This dec conc of Na+ in cell (steeper grad from interstitium into cell)
This is more favourable for the Na+/Ca2+ antiporter on the basolateral membrane of the cell so more Ca2+ reabsorbed into interstitium and then vasa recta
What is an example of a Thiazide/thiazide like diuretic?
These are 1st line antihypertenisves
Bendroflumethiazide
Indapamide
What can Thiazides be used to treat?
Essential hypertension
Mild heart failure
Osteoporosis (since increases calcium reabsorption)
Nephrogenic diabetes Insipidus polyuria
How do Potassium sparing diuretics work?
Block ENAC channels in the Collecting duct cells
Means less Na+ reabsorbed into cell and vasa recta so more water lost
How do aldosterone antagonists have a diuretic affect while also being Potassium sparing?
Aldosterone leads to more Na+/K+ ATPases to be expressed in the collecting duct so more Na+ reabsorbed so more water follows it
Also decreases Expression of ROMK channels preventing K+ leaking back into the lumen of the collecting duct
What is a potassium sparing diuretic?
Amiloride
What is an example of an aldosterone antagonist?
Spironolactone
What can aldosterone antagonists and potassium sparing diuretics be used to treat?
Secondary Hyperaldosteronism
Chronic Heart Failure
Cirrhosis
Nephrotic syndrome
Treats hypertension
Why can aldosterone antagonists and potassium sparing diuretics not be used in patients with Chronic renal failure?
Can lead to hyperkalaemia
Leads to less aldosterone being made
This leads to less ROMK being created
Means less K+ lost
Since patients with renal failure have a decreased GFR plasma conc of K+ increase
Where amino acids completely reabsorbed from the filtrate via active transport?
PCT
When theres an increase in conc of potassium the conc of what hormone increases and why?
Inc aldosterone
Leads to more ROMK being expressed so more K+ can be lost
How can loop diuretics result in hypokalaemia?
NKCC blocked
Less Na+ reabsorbed
More Na+ delivered to DCT and CD
More Na+ reabsorbed through ENAC channels
K+ lost through ROMK
Leads to hypokalaemia
What part of the nephron is the glucose reabsorbed?
PCT
Where is most of the Urate and creatinine secreted?
PCT
What is the main hormone that affects K+ excretion?
Aldosterone (due to ROMK)
What is the main transporter driving electrolyte reabsorption in the LOH?
NKCC transporter
How does aldosterone affect membrane permeability to sodium?
Increases it
