Diuretics (old)

Question 1

Loop Diuretic

• Class, Name
• MOA, location, transporter inhibited
• Actions [3] [2 electrolytes] [1 renal]

Answer 1

Sulfonamide derivative: Furosemide
- inhibits NKCC2 symporter @ THICK Ascending Limb
Actions
1: decrease reabsorption of Na, K, Cl; pull water out at collecting duct
2: Normally, K diffuses out, increases + potential of lumen, driving Mg2+ and Ca2+ reabsorption paracellularly; w [K+] ICF decreases, + electric potential of lumen decreases, [Mg,Ca] urine increases
- as less ions reabsorbed, Renal Medulla tonicity decreases - less water pulled out at collecting duct!

RECALL function of TAL: site of maintaining Medulla osmolarity by accumulating salt in interstitium

3: Produce PGs
- PGE2 inhibit sodium reabsorption by blocking NKCC2
- increases renal blood flow by vasodilation

• note NSAIDs block PG production, less transporters inhibited, hence allowing Na reabsorption;
• NSAID also block PGI2 which stimulates renin - aldosterone blocked hence less Na reabsorbed but most is absorbed at ascending limb anyways but K+ retention occurs

Question 2

Loop Diuretic uses [4]

Answer 2

Edema
Renal Failure: Cirrhosis, Nephrotic syndrome
Anion Overdose
Hyperkalaemia

Question 3

Loop Diuretic AE [4]
- explain HKMA

Note calcium reabsorbed at DCT

Answer 3

Hypokalemic Metabolic Alkalosis

• more sodium at Collecting duct, reabsorbed in exchange for potassium; H+ also secreted
• hypovolemia trigger PCT to increase reabsorption of water and bicarbonate - alkalosis

Hypomagnesemia
Loop earrings hurt your ear: Ototoxicity - avoid Aminoglycosides
Hyperuricemia

Question 4

Thiazide

• Name
• MOA, location, transporter inhibited
• Actions [2] [2 electrolytes]

Answer 4

Hydrochlorothiazide HCT
- Na-Cl symporter at DCT

Action

• Concentrates urine w NaCl
• Thiazide increases Ca2+ reabsorption; less Na ICF, more pulled in at basolateral end in exchange for Ca, Ca ICF decreases, Ca reabsorption increases

Question 5

Thiazide Uses [2]

Explain

Answer 5

Kidney stones by calcium
Nephrogenic GI
- Decreases [NaCl] blood, decrease osmolarity, decrease thirst trigger, decrease polydipsia, polyuria
- Decrease H2O, decreases plasma volume [hypovolemia], thus lowering the GFR and enhancing the absorption of sodium and water in the proximal tubule.
- hypovolemia continues but osmolarity returns

Question 6

Thiazide AE [5]

Answer 6

Hypokalemic Metabolic Alkalosis
- same mechanism, due to high Na at collecting duct
Hyperuricemia
Hyponatremia - unlike Loops

Hyperglycemia and Hyperlipidemia

Question 7

Collecting Duct
- transporters and electrolytes

Aldosterone actions

Answer 7

Sodium reabsorption by ENaC;
- coupled w K secretion and H+ secretion

Aldosterone upregulate:
ENaC at apical
Na/K pump at basolateral

Question 8

Potassium-sparing diuretics

• Location
• MOA

Answer 8

Spironolactone - Aldosterone receptor
Amiloride - Na+ Channels

• block Na reabsorption, hence block K secretion
• weakly natriuretic hence used in combination w loop diuretics (furosemide)

Question 9

PSD AE [2]

Answer 9

Hyperkalemia

Metabolic acidosis - by blocking H+ release

Question 10

Thick vs Thin Ascending Limb

Answer 10

Thick ascending - where NaCl absorbed , H2O impermeable

Thin descending - where water absorbed