Lecture 8: Drugs Acting On The Kidney Flashcards

0
Q

Where do loop diuretics act?

A

Blocks the Na/K/2Cl cotransporter system on the ascending loop of henle

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

Where do osmotic diuretics act?

A

In the efferent arterioles by modifying filtrate content

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

Where do thiazides act?

A

Blocks the Na/Cl cotransporter on the distal convoluted tubule

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

Where does amiloride work?

A

Binds to the chloride portion of the Cl/Na cotransporter in the collecting duct

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

Where does spironolactone act?

A

Binds to the sodium part of the Cl/Na cotransporter in the collecting duct

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

How do diuretics work?

A

They inhibit reabsorption of the sodium and calcium ions creating an osmotic imbalance resulting in water leaving the cells to maintain homeostasis. This water is then excreted out which decreases blood volume and blood pressure

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

How does carbonic anhydrase work?

A

the sodium hydrogen ion exchanger and acid base regulation involving carbonic acid and bicarbonate occurs in the proximal convoluted tubule.
Carbonic anhydrase is an enzyme that catalyses the formation of carbonic acid from water and CO2.
Carbonic acid is the primary source of hydrogen ions which are excreted back into the lumen through that Na/H co exchanger.

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

What is the mechanism of action of carbonic anhydrase inhibitor?

A

E.g. Acetazolamide, Methazolamide inhibits carbonic anhydrase, preventing formation of carbonic acid, and further breakdown to bicarbonate and hydrogen ions.
That whole synthetic acid base pathway is broken down or shut down, Resulting in the accumulating of hydrogen ions.
Hydrogen ions aren’t being used in the formation of carbonic acid
So They build up within the tissue
The Na/H co transporter starts to shut down.
The body’s response is to shut down or switch to the exchange system so instead so accompanying hydrogen ions out it conserves hydrogen and try to restore them. It instead, excretes the sodium ions.

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

What controls the absorption of NaCl ?

A

Aldosterone

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

What controls the absorption of water?

A

Antidiuretic hormone

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

How does aldosterone work?

A

Enhances Na reabsorption and promotes K excretion.
Its rapid effect occurs through stimulation of the Na/H exchanger by an action on membrane aldosterone receptors.
It’s delayed effect occurs by binding to receptors within the cell an directing the synthesis of a specific mediator protein which activates Na channels in the apical membrane to allow the tenasllukd passage of Na.

Long term effects by increasing the number of basolateral Na pumps.

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

How does adh work?

A

Produces sustained increase in permeability of water in the collecting duct of the nephron allowing the passive reabsorption of water.
The hormone is secreted by the posterior pituitary and binds to receptors in the basolateral membrane. The stimulation of these receptors increase the number of aquaporins in the apical membrane.

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

How is potassium maintained in the kidney?

A

K is reabsorbed in the proximal tubule and loop of henle.
In the collecting duct, K is transported into the cell from the blood and interstitial fluid by the Na/K ATPase.
K leaks into the tubule through a K selective ion channel.
Sodium passes through sodium channels in the apical membrane down the electrochemical gradient for Na.
Influx results in depolarisation of the luminal to generate a lumen negative potential difference across the cell increasing the driving force for potassium secretion,

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

When will potassium loss be increased?

A

With thiazide diuretics as more Na reaches the collecting duct.
With loop diuretics which decrease Na absorption and therefore more Na reaching the collecting duct.

In hyperaldosteronism where Na reabsorption in collecting dcuts is markedly increased which indicretly increases K excretion
NB: aldosterone may also directly increase luminal membrane K permeability

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

When will potassium loss be reduced?

A

When Na reabsorption in the collecting ducts is decreased such as with amiloride. These block the sodium channel in this part of the nephron. I.e. Potassium sparing diuretics.

Spironolactone blocks the action of aldosterone

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

How do loop diuretics work?

A

E.g furosemide, bumetanide, ‘high ceiling diuretics’
They act in the thick segment of the ascending LoH
Acts on Na/K/2Cl cotransporter to block the transport of NaCl out of the tubule into the interstitial tissue.

Furosemide has a direct inhibiting effect on the carrier by acting on the Cl- site.

16
Q

How do thiazide diuretics work?

A

Hydrochlorothiazide
Inhibits passive Na+/Cl– cotransporter by binding to the Cl- site to Reduce Na+ reabsoprtion, Reduce water reabsorption resulting in water loss. Moderately powerful diuretic agent

18
Q

How do potassium sparing diuretics work?

A

Spironolactone is an Aldosterone receptor antagonist and Binds to aldosterone receptors to block the activation/formation of Na+ channels by aldosterone. Resulting in reduced Na+ reabsorption, reduced water reabsorption and water lossAmiloride is a Na+ channel blocker. It reduces Na+ reabsorption in the collecting duct which in turn reduces water reabsorption causing water loss

19
Q

How does osmotic diuretics work?

A
  • e.g. mannitol.
  • acts on entire tubule system
  • when ingested, mannitol is incompletel absorbed or not absorbed at all so it often sits in the lumen.
  • causes alteration in osmotic pressure so body reduces passive water reabsorption which starts to attract cellular water to extracellular compartments.
  • water coming out of tissues further increases osmotic pressure
  • body stops the reabsorption of sodium which alters the electrochemical gradient in the ion exchange systems
  • results in more sodium in the lumen causing more water to move out