Diuretics Flashcards
What is diuresis?
Increased production of urine by the kidney
What is a diuretic?
Drug that causes diuresis
How do all diuretics basically work?
Decrease reabsorption of sodium ions
so more sodium ions are excreted
water follows sodium ions
so more water is excreted too
What is the proportion of filtered sodium ions normally excreted by the kidney?
Less than 1%
How are diuretics classified into different groups?
Based on the part of the nephron tubule that they act on
Based on the transporter or channel that they block
How do diuretics reach the nephron and the transporter or channel that they act on?
They are secreted into the tubular lumen of the proximal convoluted tubule
travel through the nephron to the region they act on
they block their specific transporter or channel from the inside of the tubular lumen
What are the different groups of diuretics?
Loop diuretics
Thiazide diuretics
Potassium ion sparing diuretics
What are the different groups of diuretics in order of potency?
Loop diuretics
Thiazide diuretics
Potassium-sparing diuretics
Why are loop diuretics more potent than thiazide diuretics?
Because 25% of sodium ions are reabsorbed in the thick ascending limb of the loop of Henle
Whilst only 5% of sodium ions are reabsorbed in the distal convoluted tubule
So loop diuretics cause excretion of more sodium ions than thiazide diuretics, and hence more water excretion
What region of the nephron do loop diuretics act on?
Thick ascending limb of loop of Henle
What transporter or channel do loop diuretics act on?
NKCC2 transporter
What are the effects of loop diuretics?
Reduced sodium ion reabsorption
Reduced calcium ion reabsorption
Reduced water reabsorption in the later distal convoluted tubule and collecting duct
How do loop diuretics reduce calcium ion reabsorption?
Sodium, chloride and potassium ions do not move from tubular lumen into epithelial cell
Potassium ions do not move back into tubular lumen through ROMK channel making tubular lumen more positively charged
Reduced electrical gradient for calcium ions to move from tubular lumen into interstitial fluid by paracellular route
How do loop diuretics reduce water reabsorption in the later distal convoluted tubule and the collecting duct?
Fewer sodium and chloride ions move from epithelial cell into interstitial fluid in medulla
Reduced osmolality of interstitial fluid in medulla
Less of an osmotic gradient for water to move into it through Aquaporins from the tubular lumen
What are some examples of loop diuretics?
Furosemide
Bumetanide
What region of the nephron do thiazide diuretics act on?
The distal convoluted tubule
What transporter or channel do thiazide diuretics act on?
The NCC transporter
What are the effects of thiazides?
Reduced sodium ion reabsorption
Reduced chloride ion reabsorption
Reduced water reabsorption in later distal convoluted tubule and collecting duct
Increased calcium ion reabsorption
How do thiazides reduce water reabsorption in the later distal convoluted tubule and the collecting duct?
Fewer sodium and chloride ions move from epithelial cell into interstitial fluid in medulla
Reduced osmolality of interstitial fluid in medulla
Less of an osmotic gradient for water to move into it through Aquaporins from the tubular lumen
How do thiazides increase calcium ion reabsorption?
Sodium ions do not move from tubular lumen into epithelial cell
reduced concentration of sodium ions in the epithelial cell
more of a concentration gradient for sodium ions to move from interstitial fluid into epithelial cell
increased activity of NCX on basolateral domain of epithelial cell
more calcium ions are moved from epithelial cell into interstitial fluid
so more calcium ions move from tubular lumen into epithelial cell through calcium ion uniporter on apical domain of epithelail cell
What region of the nephron do potassium-sparing diuretics act on?
Later distal convoluted tubule and collecting duct
What type of cell in the later collecting duct and distal convoluted tubule do potassium-sparing diuretics act on?
Principal cells
What are the different types of potassium-sparing diuretics?
ENaC inhibitors
Aldosterone antagonists
How do ENaC inhibitors reduce water reabsorption?
Fewer sodium ions move from epithelial cell into interstitial fluid in medulla
Reduced osmolality in medulla
Less of an osmotic gradient for water to move into it through Aquaporin channels from the tubular lumen
How do ENaC inhibitors reduce potassium ion secretion?
Sodium ions do not move from tubular lumen into epithelial cell
Tubular lumen becomes more positively charged
Less of an electrical gradient for potassium ions to move from epithelial cell through ROMK channels into tubular lumen
Fewer potassium ions move
What is an example of an ENaC inhibitor?
Amiloride
How do aldosterone antagonists bind to the aldosterone receptors?
Competitive inhibition
What is an example of an aldosterone antagonist?
Spironolactone
What is a side effect of loop diuretics and thiazides?
Hypokalaemia
How do loop diuretics and thiazides cause hypokalaemia?
Increase potassium ion secretion
How do loop diuretics and thiazides cause increased potassium ion secretion?
More sodium ions and water in later distal convoluted tubule and collecting duct
More sodium ions move from tubular lumen through ENaC into epithelial cell
more negatively charged tubular lumen
more of an electrical gradient for to potassium ions move from epithelial cell through ROMK channels into tubular lumen
Tubular fluid flows through later distal convoluted tubule and collecting duct faster
Removes potassium ions from tubular lumen
reducing their concentration in the tubular lumen
More potassium ions move from epithelial cell through ROMK channels into tubular lumen
Increases activity of BK channels
More potassium ions move from epithelial cell through BK channels into tubular lumen
Reducing blood volume and blood pressure
Activation of RAAS
Aldosterone results in increased potassium secretion
Do loop diuretics or thiazides cause hypokalaemia more often?
Thiazides cause hypokalaemia more often
How can the side effect of loop diuretics and thiazides be overcome?
Given in combination with potassium-sparing diuretic
Given with potassium ion supplements
What is a side effect of potassium-sparing diuretics?
Hyperkalaemia
How do potassium-sparing diuretics cause hyperkalaemia?
Decrease potassium ion secretion
How do potassium-sparing diuretics decrease potassium ion secretion?
Sodium ions do not move from tubular lumen through ENaC into epithelial cell
tubular lumen is more positively charged
less of an electrical gradient for potassium ions to move from epithelial cell through ROMK channels into tubular lumen by facilitated diffusion
What are loop diuretics used to treat?
Hypertension
Oedema
Hypercalcaemia
How do loop diuretics treat hypertension?
Increase production of prostaglandins
give vasodilation and venodilation
reducing total peripheral resistance, afterload, preload
How do loop diuretics treat oedema?
Reduce extracellular fluid volume
What are thiazide diuretics used to treat?
Hypertension
Oedema
How do thiazide diuretics treat hypertension?
Cause vasodilation
reducing total peripheral resistance, afterload
What are some examples of conditions that cause oedema?
Heart failure
Nephrotic syndrome
Renal failure
Liver cirrhosis
What is spironolactone used to treat?
Hypertension
Oedema
Which diuretic is preferably used to treat hypertension?
Thiazide
If this doesn’t work, or if the hypertension is caused by primary hyperaldosteronism
then spironolactone is used
Which diuretic is preferably used to treat heart failure? Why?
Spironoloactone
because it reduces mortality
Which diuretic is preferably used to treat oedema caused by liver cirrhosis?
Spironoloctone
What are the side effects of diuretics in general?
May cause hyponatraemia
May cause hypovolaemia
May cause gout
What are the effects of aldosterone antagonists?
Reduced sodium ion reabsorption
Reduces water reabsorption
Reduced potassium ion secretion
How may diuretics cause gout?
Diuretics compete with uric acid for secretion into the proximal convoluted tubule
less uric acid secreted
more uric acid in the blood
precipitates out as urate crystals causing gout
