Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

LCRS Pharmacology and Therapeutics > Diuretics > Flashcards

Diuretics Flashcards

1
Q

What are diuretics?

A

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Where is a lot of sodium reabsorbed?

A

In the proximal tubule

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

How dos sodium diffuse into the epithelial cell?

A

On the apical side there are Na+ channels

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What happens once sodium is in the epithelial cell?

A

Na+/K+ ATPase pumps sodium out of the cell and into the blood in exchange for K+

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What effect does the oncotic pressure exerted by the proteins in the capillaries have?

A

It exerts an important force in drawing water into the capillaries

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

How much protein is there in the filtrate?

A

None

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What is another route of ion and water movement apart from the main one?

A

Paracellular pathway

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What is the paracellular pathway dependent on?

A

Gap junctions between cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Where is there a lot of paracellular pathway in use?

A

Proximal tubule has large gap junctions between cells so there is a fair amount of movement of ions and water via the paracellular pathway

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Apart from water and ions, what else is reabsorbed lots in the proximal tubule?

A

Glucose and amino acids

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What does reabsorption of glucose and amino acids tend to be coupled with?

A

Sodium reabsorption

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What is sodium exchange linked to?

A

Carbonic anhydrase

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What does carbonic anhydrase do?

A

It converts CO2 + H2O to HCO3- + H+ (reversible reaction)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What happens after H+ and HCO3- is filtered by the glomerulus into the filtrate?

A

They then interact with membrane bound carbonic anhydrase which converts it to CO2 and H2O

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What can CO2 and H2O do?

A

Freely diffuse into the cell

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What happens once CO2 and H2o enters the cell?

A

They are acted on by carbonic anhydrase that converts them back to H+ and HCO3-

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

What happens to the H+ and HCO3- once formed in the cell?

A

The HCO3- ions are reabsorbed into the capillaries along with sodium (Na+/HCO3- co transport)
The H+ is used to drive the Na+/H+ exchanger at the apical membrane

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

What is the end result of the interaction between sodium exchange and carbonic anhydrase?

A

A lot of sodium, bicarbonate and water reabsorption

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

How are exogenous agents (drugs) removed by the kidneys?

A

They can be removed through transport proteins that pick up the drugs as they pass through the kidneys and transport them into the lumen

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

What percentage of filtered fluid is reabsorbed in the PCT?

A

About 65-70%

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

In the loop of Henle, how do the two limbs differ in permeability?

A

The descending limb is freely permeable to water

Ascending limb is not permeable

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

How does water transport in the descending limb work?

A

It is very straight forward- water moves straight from the tubule lumen, through the epithelial cells into the interstitium

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

What is the Na+/K+/2Cl- transporter responsible for?

A

Transporting these three ions into the epithelial cels from the lumen in the ascending limb

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

Which two channels on the basolateral membrane are responsible for moving Na+/K+/2Cl- into the intersitium?

A

Na+/K+ ATPase
K+/Cl- cotransporter

These are present through the nephron because it maintains the concentration gradient that allows absorption of electrolytes from lumen into the cell

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

Which limb of the loop of Henle can reabsorb Na+?

A

Ascending

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

What happens to the interstitial after sodium transport into it?

A

It becomes hypertonic and fluid in ascending limb becomes hypotonic

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

What effect does the medullary interstitium becoming hypertonic have?

A

It will draw more water from descending limb so fluid in descending limb will become more hypertonic because you’re removing water but sodium is being retained

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

What is the end result of the transport in loop of Henle?

A

You have very concentrated interstitium

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

Why is the countercurrent effect called countercurrent?

A

Capillaries that pass through this pass in the opposite direction to the flow of fluid

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

What happens to a lot of fluid in the interstitium?

A

It will end up in the capillaries

31
Q

What does the interstitium have a profound effect on as it becomes more concentrated?

A

The collecting duct which is incredibly permeable to water under the influence of vasopressin

32
Q

What is the effect of the interstitium on collecting duct very important for?

A

Making sure that we don’t lose too much fluid

33
Q

In the early distal tubule, what happens to any sodium left in the filtrate?

A

It will be transported by the Na+/Cl- transporter i the apical membrane and eventually it will get to the capillaries

34
Q

What becomes important as you move to the late distal tubule?

A

Aldosterone and aquaporins

35
Q

What are aldosterone and vasopressin very important in?

A

Mediating collecting duct function

36
Q

What is aldosterone and what does it do?

A

A steroid which binds to mineralocorticoid receptors in the cell and acts via the nucleus to increase production of Na+ channels and Na+/K+ ATPase

37
Q

What does aldosterone stimulate?

A

The production and insertion of the machinery that is required for sodium reabsorption in the collecting duct (provided that the concentration gradient is maintained by Na+/K+ ATPase_

38
Q

What does vasopressin do?

A

Stimulates and assembles AQP2 (aquaporin 2) molecules that allow water to follow the sodium

39
Q

How do the majority of diuretics work?

A

They inhibit the reabsorption of Na+ and Cl- i.e. increase excretion
They increase the osmolarity of tubular fluid i.e. decrease the osmotic gradient across the epithelia

40
Q

What are the 5 main classes of diuretic drugs?

A

Osmotic diuretics e.g. Mannitol
Carbonic anhydrase inhibitors e.g. Acetazolamide
Loop diuretics e.g. Frusemide
Thiazide diuretics e.g. Bendrofluazide
Potassium-sparing diuretics e.g. Amiloride, spironolactone

41
Q

What sort of diuretics aren’t classically used as diuretics (not used for that purpose clinically)?

A

Osmotic diuretics and carbonic anhydrase inhibitors

42
Q

Where do diuretics work?

A

Throughout the nephron

43
Q

How do osmotic diuretics e.g. Mannitol work?

A

They are pharmacologically inert- all it does is increase the osmolarity of the plasma and kidney filtrate- it is filtered by the glomerulus but is not reabsorbed
Increasing the osmolarity of the filtrate will mean that less water leaves the lumen and is reabsorbed

44
Q

What are osmotic diuretics clinically used for?

A

They are used to raise plasma osmolarity to draw out fluid from cells and tissues

45
Q

How do carbonic anhydrase inhibitors (e.g. acetazolamide) work?

A

It blocks carbonic anhydrase which will prevent H+ and HCO3- from entering the epithelial cells form the lumen so there will be less Na+/H+ exchange so bicarbonate remains in the lumen and less sodium is reabsorbed (via Na+/H+ exchanger). As there is more sodium in the lumen, water remains in the lumen thus increasing the urine volume

46
Q

What do loop diuretics act on?

A

Na+/K+/2Cl triple transporter in the ascending limb of the loop of Henle

47
Q

How do loop diuretics work?

A

They target the Na+/K+/2Cl transporter which means that sodium reabsorption in ascending limb of loop of Henle is greatly impaired so more sodium is retained in the lumen

48
Q

How powerful are loop diuretics?

A

They are very powerful and can promote 15-20% fluid loss

49
Q

What else do loop diuretics remove?

A

Potassium recycling

50
Q

What is potassium recycling?

A

You have K+ being reabsorbed via the triple transporter
It is also exchanged for Na+ by the Na+/K+ protein on the basolateral membrane. This potassium then diffuses back out of the cell into the lumen

51
Q

What does potassium recycling lead to?

A

It means that there is always a certain amount of potassium that is driving other positive ions across the cell via the paracellular pathway
There is positive lumen potential that drives positive ions across the epithelium via the paracellular pathway

52
Q

What effect do loop diuretics have by blocking potassium recycling?

A

They interfere with the positive lumen potential so you tend to lose some other positive ions in the urine as well- Ca2+ and Mg2+ in the urine because they aren’t being driven via the paracellular route into the interstitium

53
Q

What is the main effect of loop diuretics?

A

Large increase in urine volume and Na+,Cl= and K+ loss

54
Q

What is the main use of loop diuretics?

A

Oedema

55
Q

What are the unwanted effects of loop diuretics?

A

Hypovolaemia and hypotension
K+ loss (and Ca2+ and Mg+)
Metabolic alkalosis

56
Q

What do thiazide diuretics act on?

A

Distal tubule

57
Q

Why are thiazide diuretics not as powerful as loop diuretics?

A

The distal tubule is only responsible for about 5-10% of fluid

58
Q

How do thiazide diuretics work?

A

They bind to and block the Na+/Cl- cotransporter so more Na+ and Cl- is lost in the urine
If used at high dose they can cause 5-10% fluid loss

59
Q

What is the main effect of thiazide diuretics?

A

Moderate increase in urine volume and increase in Na+, Cl- and K+ loss (and Mg2+ loss)

60
Q

What are thiazide diuretics used for?

A

Cardiac failure
Hypertension (due to decrease in blood volume)
Idiopathic hypercalciuria
Nephrogenic diabetes insipidus

61
Q

What are the unwanted effects of thiazide diuretics?

A

K+ loss- metabolic alkalosis

Inhibits insulin secretion

62
Q

What is the problems with loop and thiazide diuretics related to?

A

Release of renin by macula densa cells

63
Q

Why is there a problem with diuretics and macula densa cells?

A

The protein on the apical membrane of the macula densa cells is the same as the ones seen in the loop of Henle- loop diuretics block this and prevent entry of sodium into the macula densa cells

64
Q

Where are macula densa cells found?

A

Distal tubule

65
Q

What happens after a diuretic has been used for a long time?

A

It has caused a fair amount of Na+ and Cl- loss so will eventually reduce concentration of Na+ in the tubular fluid because the amount in the blood decreases so amount being filtered reduces so amount reaching macula densa decreases

66
Q

What is a decrease in Na+ reaching macula densa a stimulus for?

A

Renin secretion which will then stimulate increase in Na+ reabsorption
This is a general principle for all diuretics that they stimulate renin secretion

67
Q

Why is the renin secretion a problem?

A

Because you’re trying to reduce Na+ and fluid reabsorption and hence reduce blood pressure but you’re activating a system that is going to cause vasoconstriction and promote aldosterone production which will increase Na+ reabsorption- negates the effect of droogs

68
Q

How is the effect of renin secretion commonly avoided?

A

ACE inhibitors are administered with diuretics

69
Q

Where do potassium sparing diuretics (amiloride and spironolactone) act?

A

In the late distal tubule and collecting duct

70
Q

What are the classes of potassium sparing diuretics?

A

Aldosterone receptor antagonists e.g. spironolactone

Inhibitors of aldosterone-sensitive Na+ channels

71
Q

What is spironolactone?

A

Mineralocorticoid receptor antagonist so prevents aldosterone from having its effect of increasing Na+ reabsorption so there is a decrease in Na+ and a diuretic effect

72
Q

What is the main effect of potassium sparing diuretics?

A

Small increase in urine volume and loss of Na+

73
Q

What is spironolactone used for?

A

Hypertension and heart failure

Hyperaldosteronism

74
Q

What are the unwanted effects of potassium sparing diuretics?

A

Hyperkalaemia- metabolic acidosis

Can cause gynaecomastia, menstrual disorders and testicular atrophy

LCRS Pharmacology and Therapeutics (33 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions