Renal Diuretics Flashcards
What do Diuretics cause?
Diuretics cause an increase in urine output (diuresis)
What do diuretics produce an increased excretion of?
Many diuretics also produce increased excretion of
Na (natriuresis) and K (producing hypokalaemia)
What are diuretics used in?
used in hypertension,
acute pulmonary oedema, heart failure
What are the 2 major groups of diuretics?
- Mainly affect H20 excretion
- Increase in electrolyte excretion
What is included in diuretics that mainly affect H20 excretion?
- Water
- Ethanol(Reduce ADH release)
- Osmotic diuretics
What is included in diuretics that cause an increase in electrolyte excretion?
- Carbonic anhydrase inhibitors
- Loop diuretics
- Thiazides
- K-sparing diuretics
What is the mechanism of action of diuretics on site 1?
Reabsorption of Na with passive movement of
organic molecules (glucose, amino acids) and H2O
What is the mechanism of action of diuretics on site 2?
Reabsorption of Na for H (Na/H exchanger) - Role of carbonic anhydrase
Where are both site 1 and site 2 located in the nephron?
Proximal convoluted tubule
Where is site 3 located in the nephron?
Loop of Henle
What is the mechanism of action of diuretics on site 3?
Transport of NaCl by a co-transporter for Na, K, 2Cl
-Interstitial fluid becomes hypertonic, aiding reabsorption of H20 from the collecting duct(controlled by ADH)
What is the permeability of thick ascending liip of henle to H20 like?
Thick ascending Loop of Henle is NOT permeable to H2O
Where are site 4, site 5 and site 6 located in the nephron?
Distal convoluted tubule
What is the mechanism of action on site 4 of diuretics?
Reabsorption of Na/Cl (co-transporter) followed by H2O
What is the mechanism of action on site 5 of diuretics?
Na is reabsorbed (through ENaC channels) in exchange for K efflux
(through K channels) - stimulated by aldosterone
What is the mechanism of action on site 6 of diuretics?
Na is reabsorbed and H+ lost via Na-H exchanger
- stimulated by aldosterone
What can an overactive site 5 produce?
Overactive Site 5 can produce K+ loss and plasma hypokalaemia
What can an overactive site 6 produce?
Overactive Site 6 can produce plasma alkalosis due to increased H+ excretion
What is an example of agent that mainly affect H20 excretion and how is it administred?
Mannitol
-Usually administered i.v.
How does mannitol work?
-High concentrations in plasma
-Causes increased osmolarity in tubules
-Results in decreased reabsorption of H20
Where does mannitol act at?
Acts at PCT, DCT, and collecting duct
What are the uses of mannitol?
-Reduce intracranial and intraocular pressure
-Prevent acute renal failure
-Excrete some types of poisoning
How does mannitol work to reduce intracranial and intraocular pressure?
-Mannitol does not enter the CNS
-Creates an osmotic gradient from cells to plasma
-H2O leaves the CNS (CSF into plasma)
-H2O leaves plasma into tubules and then urine
How do diuretics that affect electrolyte excretion work?
Drugs increase urine flow by increasing excretion of Na (natriuresis)
– where Na goes H2O follows (osmosis)
What is the major determinant of ECFV?
NaCl is the major determinant of extracellular fluid volume (ECFV)
What will NaCl excretion from ECF lead to?
Increased NaCl excretion leads to decreased ECFV leads to decreased Blood vol which leads to decreased Cardiac output which ultimately decreases Oedema
What is an example of a diuretic that affects electrolyte excretion and what type is it?
Carbonic anhydrase inhibitors
-Acetazolamide
How does acetazolamide work including what site it acts on?
Inhibit the activity of CA - decrease formation of H+ / HCO3- in the luminal cells of PCT (Site 2)
Less Na+ uptake - less H2O uptake
What are non renal effects that acetazolamide can be used in?
In glaucoma, aqueous humor formation
is dependent on carbonic anhydrase activity
What is an example of a loop diuretic?
Furosemide
What is the mechanism by which furosemide works?
Inhibit Na/K/Cl co-transporter at thick ascending loop of Henle (Site 3)
decreasing Reabsorption of Na, K, and 2Cl – marked loss of these electrolytes
What does furesomide prevent concentration of and therefore how does this impact water loss?
Prevents concentration of cortico-medullary interstitial fluid and therefore
reduces effect of ADH on the collecting duct (less osmotic drive) - Increasing H2O loss
What are the uses of furosemide?
- Chronic heart failure
- Acute renal failure
- Acute pulmonary oedema
What does furosemide do in chronic heart failure?
- Decreases ECFV therefore decreases congestion
How does furosemide produce vasodilation?
Produces vasodilation due to increased PCI2 released in blood vessels
How does furosemide work in acute renal failure?
Increase renal blood flow
How does furosemide work in acute pulmonary oedema?
Decrease capillary pressure
What are compensation mechanisms/side effects at site 5 and site 6 due to furosemide?
-Site 5 - Increase Na uptake via ENaC – increase K excretion – K loss (hypokalaemia)
-Site 6: Increase Na uptake via Na/H exchanger– H loss (metabolic alkalosis)
What is an example of a thiazide diuretic?
Bendrofluazide
What is the mechanism of action of bendrofluazide?
Inhibit Na/Cl uptake via co-transporter at distal convoluted tubule (Site 4)
What is the compensation mechanism/ side effects of bendrofluazide at site 5 and site 6?
Site 5: Increase Na uptake via ENaC – increase K excretion – K loss (Hypokalaemia)
Site 6: Increase Na uptake via Na/H exchanger – H loss (Metabolic alkalosis)
What are the uses of bendrofluazide?
-Treatment of hypertension
-Treatment of mild heart failure
How does the treatment of hypertension by bendrofluazide work?
- Diuresis causes a decrease in blood volume therefore a decrease in cardiac output
- Major effect is causing vasodilation which results in a decreased TPR
How does the treatment of mild heart failure work by bendrofluazide?
Decreased ECFV leads to decreased Oedema
What is the mechanism of K-sparing diuretics?
Important as they reduce Na reabsorption without losing K
- counter the powerful electrolyte secretions of diuretics such as frusemide -
Where do K-sparing diuretics act?
Act at end of DCT and collecting duct (Sites 5 + 6)
What are examples of K-sparing diuretics?
- Spironolactone
- Amiloride
What type of antagonist is spironolactone and what sites does it act on?
Competitive antagonist of aldosterone
at sites 5 and 6
What conditions is spironolactone used for?
CVS diseases linked to overproduction of
aldosterone volume overload
e.g., Heart failure
What does amiloride do and what site does it act on?
Reduces Na reabsorption and K loss
Blocks ENaC at site 5
How do ACE inhibitors work?
Decrease Ang II formation which decreases aldosterone
