Lecture 8: Drugs Acting On The Kidney Flashcards
Where do loop diuretics act?
Blocks the Na/K/2Cl cotransporter system on the ascending loop of henle
Where do osmotic diuretics act?
In the efferent arterioles by modifying filtrate content
Where do thiazides act?
Blocks the Na/Cl cotransporter on the distal convoluted tubule
Where does amiloride work?
Binds to the chloride portion of the Cl/Na cotransporter in the collecting duct
Where does spironolactone act?
Binds to the sodium part of the Cl/Na cotransporter in the collecting duct
How do diuretics work?
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 does carbonic anhydrase work?
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.
What is the mechanism of action of carbonic anhydrase inhibitor?
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.
What controls the absorption of NaCl ?
Aldosterone
What controls the absorption of water?
Antidiuretic hormone
How does aldosterone work?
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 does adh work?
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 is potassium maintained in the kidney?
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,
When will potassium loss be increased?
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
When will potassium loss be reduced?
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
