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YR2 LCRS Pharm > Diuretics > Flashcards

Diuretics Flashcards

1
Q

What are diuretics?

A

Drugs that act on the renal tubule to promote excretion of Na+, Cl- + H2O

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2
Q

What percentage of filtered fluid is reabsorbed in the proximal tubule?

A

65-70%

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3
Q

How does water move into the epithelial cells from the lumen in the proximal tubule?

A

Osmosis: follows the diffusion of Na+ into the cell

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4
Q

What important protein is present on the basolateral membrane of epithelial cells along most of the tubule and is responsible for maintaining the concentration gradient that allows sodium reabsorption?

A

Na+/K+ ATPase

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5
Q

What other force is present, within the interstitium, that helps draw water in from the tubule?

A

Oncotic pressure: proteins in the blood in the arterioles draws water towards blood

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6
Q

Other than transcellularly, what other route is there for the movement of ions and water?

A

Paracellular pathway

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7
Q

What is the paracellular pathway dependent on?

A

Gap junctions

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8
Q

What 2 molecules in the filtrate are reabsorbed in the proximal tubule coupled with Na+ reabsorption? Which protein allows this movement?

A

Glucose
Amino acids
Sodium-Hydrogen exchanger protein

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9
Q

Explain how sodium exchange is linked to carbonic anhydrase?

A

HCO3- + H+ are filtered in the glomerulus
Carbonic anhydrase converts them to H2O + CO2, which freely diffuse into the proximal tubule epithelial cell
Inside the epithelial cell, carbonic anhydrase converts them back to H+ + HCO3-
HCO3- is cotransported with Na+ into the interstitium
H+ is exchanged for Na+ at the apical membrane via the Na+/H+ exchanger

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10
Q

How are exogenous agents removed in the kidneys?

A

Drugs are removed by transport proteins that pick up drugs as they pass through the kidneys + transport them into the lumen

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11
Q

Describe the permeability of the loop of Henle to water.

A

Descending limb is freely permeable to water but not to ions
Ascending limb is impermeable to water but is permeable to ions

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12
Q

What is the main channel present on the apical membrane of the epithelial cells of the ascending limb of the loop of Henle?

A

Na+/K+/2Cl- cotransporter

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13
Q

What channels are present on the basolateral membrane of the epithelial cells of the ascending limb of the loop of Henle?

A

Na+/K+ ATPase

K+/Cl- cotransporter

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14
Q

Describe how the counter-current system is established.

A

Filtrate travels down the LOH + as it goes up the ascending limb, Na+ moves from the tubule to the interstitium thus making the interstitium hypertonic + tubular fluid hypotonic.
Then, more fluid comes down the descending limb (permeable to water) + the hypertonic interstitium attracts water + increases reabsorption of water from the tubule into the interstitium
This increases the conc. of fluid reaching the ascending tubule where even more Na+ will be reabsorbed + move into the interstitium
This occurs repetitively, resulting in a hypertonic interstitium + hypotonic tubular fluid leaving the LOH
Hypertonic interstitium is also responsible for increasing water reabsorption in the CD (mediated by vasopressin)

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15
Q

What are the main channels on the apical membrane of epithelial cells of the distal tubule?

A

Na+/Cl- cotransporter

Aldosterone dependent sodium channels

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16
Q

Which channels are found on the basolateral membrane of the epithelial cells of the distal tubule?

A

Na+/K+ ATPase

K+/Cl- cotransporter

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17
Q

Which aquaporin molecules are found in epithelial cells of the distal tubule?

A

AQP2: apical membrane

AQP3/AQP4: basolateral membrane

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18
Q

Which vasopressin receptors are present on collecting duct cells?

A

V2 receptors

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19
Q

Describe the effect of aldosterone on collecting duct cells.

A

Aldosterone stimulates production of Na+ channels + Na+/K+ ATPases

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20
Q

Describe the effect of vasopressin on collecting duct cells.

A

Vasopressin stimulates production + assembly of AQP2 molecules thus increasing the ability of the CD to reabsorb water

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21
Q

List the five groups of diuretics.

A 
Osmotic Diuretics  
Carbonic Anhydrase Inhibitors  
Loop Diuretics  
Thiazide Diuretics  
Potassium Sparing Diuretics
22
Q

Give an example of an osmotic diuretic.

A

Mannitol

23
Q

Describe the mechanism of action of osmotic diuretics.

A

Increases plasma + urine osmolarity
Filtered by the glomerulus but not reabsorbed
Increasing osmolarity of filtrate means less water leaves the lumen + is reabsorbed

24
Q

What are osmotic diuretics used for?

A

Mainly used for their effect in increasing plasma osmolarity –they draw out fluid from cells + tissues (e.g. in oedema)

25
Q

Give an example of a carbonic anhydrase inhibitor

A

Acetazolamide

26
Q

Give an example of a loop diuretic.

A

Frusemide (furosemide)

27
Q

How much fluid loss can loop diuretics cause?

A

15-30%

28
Q

What is the target of loop diuretics?

A

Na+/K+/2Cl- cotransporter in ascending limb of LOH

29
Q

Explain how loop diuretics exert their diuretic effect.

A

Block the triple transporter thus reducing reabsorption of Na+ in the ascending limb
This increases tubular fluid osmolarity thus reducing water reabsorption so urine fluid volume increases

30
Q

Explain why loop diuretics cause an increase in urinary excretion of Mg2+ and Ca2+.

A

K+ recycling, in normal conditions, means a certain amount of K+ in the tubular fluid maintains the positive lumen potential + drive other positively charged ions (Mg2+ + Ca2+) into the interstitium via the paracellular pathway
Loop diuretics cause loss of K+ recycling meaning there is insufficient K+ in the lumen to drive the other positive ions through the paracellular pathway so you get increased urinary excretion of Mg2+ + Ca2+

31
Q

Why do loop diuretics cause an increase in K+ loss?

A

Loop diuretics increase the concentration of Na+ in the tubular fluid that is reaching the distal tubule
So there is increased Na+/K+ exchange in distal tubule –> increased K+ loss

32
Q

What are the main uses of loop diuretics?

A

Oedema + Heart failure

33
Q

What are 6 unwanted effects of loop diuretics?

A 
Hypovolaemia 
Hypotension  
Hypokalaemia 
Metabolic Alkalosis
Hyperuricemia
Hyponatremia
34
Q

Give an example of a thiazide diuretic.

A

Bendrofluazide

35
Q

Where do thiazide diuretics act and what do they act on?

A

Act in the distal tubule

Bind to the Na+/Cl- cotransporter

36
Q

How much fluid loss can thiazide diuretics cause?

A

5-10% fluid loss

37
Q

What effect do thiazide diuretics have on Mg2+ and Ca2+?

A

Increase in Mg2+ + Ca2+ reabsorption

unknown mechanism

38
Q

What are the main uses of thiazide diuretics?

A

Hypertension

Heart failure

39
Q

What are 6 unwanted effects of thiazide diuretics?

A 
Hypovolaemia 
Hypotension  
Hypokalaemia 
Metabolic Alkalosis (increased Na+/K+ exchange causes increased K+ loss)
Hyperuricemia
Hyponatremia
40
Q

What effect do loop diuretics have on the macula densa cells?

A

Macula densa cells have the same Na+/K+/2Cl- cotransporter that is present in the ascending limb of the LOH + is targeted by loop diuretics
This means loop diuretics prevent the entry of Na+ into macula densa cells, thus stimulating renin secretion

41
Q

Where are macula densa cells found?

A

At the top of the ascending limb of the LOH

where it comes very close to the afferent arteriole

42
Q

Explain the counter-productive effects of loop and thiazide diuretics on the renin-angiotensin system.

A

They cause loss of Na+ in the urine, so cause reduced Na+ in the blood meaning less Na+ is filtered in the glomerulus + hence less Na+ reaches the macula densa cells
Also reduce blood volume + pressure
Both reduction in Na+ reaching the macula densa + reduced renal perfusion pressure are stimuli for renin secretion
This leads to aldosterone production, which promotes Na+ reabsorption (hence counterproductive to the desired diuretic effects)

43
Q

What measure can be taken to prevent the actions of unwanted activation of RAAS when using diuretics?

A

Give ACE inhibitors with the diuretics

44
Q

What are the two classes of potassium sparing diuretic? Give an example of a drug that falls into each class.

A

Aldosterone receptors antagonist: spironolactone

Inhibitors of aldosterone-sensitive sodium channels: amiloride

45
Q

How much fluid loss can potassium-sparing diuretics cause?

A

5%

46
Q

Describe the effects of potassium-sparing diuretics.

A

Reduce Na+ reabsorption in the late distal tubule, which leads to increased tubular osmolarity
Results in reduced water reabsorption from the tubular fluid in the CD
Also lead to increased H+ retention (because of reduced Na+/H+ exchange)

47
Q

What is the main use of amiloride?

A

Given with K+ losing diuretics

48
Q

What is the main use of spironolactone?

A

Hypertension/ heart failure (alongside loop diuretic)

49
Q

State an unwanted effect of K+ sparing diuretics.

A

Hyperkalaemia: metabolic acidosis (due to less Na+/K+ exchange)

50
Q

By what mechanisms of action can diuretics work?

A

Inhibit reabsorption of Na+ + Cl- (increase excretion)

Increase osmolarity of tubular fluid (decrease osmotic gradient across epithelia)

51
Q

How do thiazides exert their diuretic effect?

A

Inhibit Na+ + Cl- reabsorption in early distal tubule

Increase tubular fluid osmolarity, decreasing water reabsorption in the CD

52
Q

Why can diuretics cause hyperuricemia?

A

Diuretics + uric acid use the same transport protein to access tubular cells, thus presence of diuretics means there is competition for transporters

YR2 LCRS Pharm (34 decks)

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