Drugs And Membrane Transporters: Renal Transport Systems (week 1)

Question 1

what are diuretics

Answer 1

a class of medications that promote diuresis which is increased production of urine. commonly used to help remove excess salt and water from the body by increasing urine output. can be used to treat various medical conditions and are often prescribed for managing conditions related to fluid retention and high blood pressure.

Question 2

explain osmotic diuretics

Answer 2

site of action:
-proximal tubules
- Loop of Henle
- collecting duct
Mechanism of action :
-Inhibition of water and Na+ reabsorption

Question 3

explain carbonic anhydrase inhibitors

Answer 3

Site of action:
-Proximal tubules
Mechanism of action:
-inhibition of bicarbonate reabsorption

Question 4

explain loop diuretic

Answer 4

site of action:
loop of Henle (thick ascending limb)
Mechanism of action:
-inhibition of Na+, K+ and Cl-

Question 5

explain thiazide

Answer 5

site of action:
-Early distal tubule
Mechanism of action:
-inhibition of Na+, Cl- co-transport

Question 6

explain K+ sparring diuretics

Answer 6

site of action:
-Late distal tubule
-collecting duct
Mechanism of action:
-inhibition of Na+, reabsorption and K+ secretion.

Question 7

give types of loop diuretics

Answer 7

furosemide, bumetanide - these act on the chloride-binding site and directly inhibit the carrier.

Question 8

how do loop diuretics work

Answer 8

inhibit the Na+/K+/2Cl co-transporter (NKCC2) in the thick ascending loop of henle. leads to a decrease in the Na+ and Cl- reabsorption. (blocks transport of NaCl out of the tubule into the interstitial tissue.

25% of the filtered of Na is reabsorbed in the TAL, loop diruetics have a profound diuretic action.

Question 9

what happens when NKCC2 is inhibited

Answer 9

significant increase in conc of ions in the tubule and decrease hypertonicity in the surrounding interstitium

less water to be reabsorbed into the blood. more urine to less blood volume

Question 10

what is hypokalemia

Answer 10

abnormally low levels of potassium, happens when the NKCC2 is blocked and Na+, K+ and Cl- cannot be reabsorbed.

Question 11

give examples of thiazide diuretics

Answer 11

hydrochlorothiazide. chlorothiazide, bendroflumethiazide

Question 12

what are thiazde diuretics and how do they work and what are they used for

Answer 12

they are used to treat low blood pressure and congestive heart failure, oedema rising due to heart failure, cirrhosis, chronic kidney failure, corticosteroid medications, and nephrotic syndrome.

they act to inhibit the reabsorption of Na+ and Cl- from the distal convoluted tubules in the kidneys by blocking the thiazide sensitive Na+ - Cl- symporter.

Also increases Ca2+ reabsorption at the distal tubule.

By lowering the sodium concentration in epithelial cells, thiazides increase the activity of the Na+/Ca2+ antiporter on the basolateral membrane to transport more Ca2+ into the interstitium.

Question 13

what happens when the NCC is blocked

Answer 13

stops the reabsorption of sodium and chlorine ions from the urine to the blood, leading to increased secretion of water.

Lowering the Na+ concentration inside the epithelial cell increases the activity of the Na+/Ca2+ antiporter on the basolateral membrane to transport more Ca2+ into the blood and remove Na+ from the blood

Question 14

Thiazide diuretic contraindications

Answer 14

Hypotension
 Gout
 Renal failure
 Lithium therapy
 Hypokalemia
 May worsen diabetes

Thiazides reduce the clearance of uric acids since they compete for the same transporter and therefore raise the levels of uric acid in the blood.

Thiazides cause loss of blood potassium while conserving blood calcium

Question 15

explain potassium loss with thiazides
3 mechanisms

Answer 15

1) When sodium is not efficiently reabsorbed, the electrical gradient for potassium secretion is diminished, leading to increased potassium loss in the urine

2) When aldosterone levels rise, the kidney excretes more potassium, contributing to potassium loss

3) Thiazide diuretics can have a direct effect on the renal tubules, stimulating the secretion of potassium into the urine.

Regardless thiazide will cause a loss of K, Na, Cl to some extent

Question 16

what are the 2 aldosterone antagonists

Answer 16

spironolactone and eplerenone

Question 17

In K+ sparing diuretics what do aldosterone antagonists do

Answer 17

aldosterone signals cells to kick out Na+ and bring in K+
antagonists block the effects of aldosterone, keeps sodium out and potassium in, reducing sodium reabsorption and potassium secretion

Question 18

name two Na+ inhibitors and explain how they work

Answer 18

Amiloride and triamterene
- inhibit Na+ reabsorption by blocking ENaC on the apical membrane and reduce K+ secretion by a downstream reduction in Na+/K+ ATPase activity on basal lateral membrane.

Question 19

what is Hyperkalaemia and what can cause it

Answer 19

having too much potassium in the blood, can be cause by kidney issues or K+ sparing diuretics

Question 20

drug interactions loop diuretics

Answer 20

Greater risk of hypokalaemia
change in plasma concentrations of drugs excreted by the kidney

Question 21

drug interactions thiazides

Answer 21

efficacy is reduced by NSAIDs
drugs that contribute to hypokalaemia should be avoided

Question 22

drug interactions Potassium-sparing diuretics

Answer 22

ACE inhibitors and angiotensin receptor antagonists increase plasma K+ significantly contribute to hyperkalaemia