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Flashcards in Diuretics Deck (20):
1

PK for diuretics - role of PCT

organic anion transporters on basolateral membrane of PCT allows drug entry from blood --> cell

2

Osmotic diuretics

mannitol
rarely used in clinical practice
Injected into blood, freely filtered
Osmotically active - holds water in urine
more urine produced

3

PCT diuretics

osmotic diuretics
carbonic anhydrase inhibitors

4

Carbonic anhydrase inhibitors

Prototype: acetazolamide
MOA: inhibits CA, reduces amount of sodium and bicarbonate resorption
- sodium retained in lumen leads to downstream loss of potassium
- No bicarbonate resorption - becomes acidotic
- Na/H exchanger pulls sodium into cell and pushes H+ into lumen (driven by Na gradient created by Na/K ATPase)
- H+ ions used to reclaim filtered bicarb from lumen, through action of CA
1) H+ combines with HCO3 --> H2CO3 in filtrate
2) CA converts H2CO3 --> H2O + CO2
3) CO2 enters cell - reverse reaction, generate H+ and HCO3
4) HCO3 moves into blood, H+ recycled back into lumen

- works early in PT, so not as effective on Na handling

5

Loop of Henle diuretics

loop diuretics

6

Loop diuretics

Prototype: furosemide (Lasix)
MOA: inhibits NKCC - less Na, K, Cl reabsorption
- no electrochemical gradient set up to drive paracellular resorption of Ca, Mg (less Cl- in interstitium and less K+ in lumen)
- downstream effects: channels in DT stuck reabsorbing Na, can't reabsorb K+ and H+, leading to metabolic alkalosis & hypokalemia

7

DCT diuretics

thiazides

8

Thiazide diuretics

Prototype: HCTZ, metolazone (not technically a thiazide but same action, also highly potent)
MOA: inhibits NCC transporter
- more Na and Cl in lumen
- ds effects: metabolic alkalosis and hypokalemia (impaired K/H resorption due to excess Na)
- increased Ca+ reabsorption results in hypercalcemia (can reduce incidence of kidney stones, help in osteoporosis)

9

CD diuretics

aldosterone antagonists (K+ sparing)
ENaC blockers (K+ sparing)

10

Aldosterone antagonists/K+ - sparing diuretics

Prototype: spironolactone, epleronone
MOA: antagonist against mineralocorticoid receptor (MR)
- Normally, aldosterone binds MR, translocates to nucleus and upregulates ENaC and Na/K ATPase
- less Na+ reabsorption, producing natriuresis and diuresis
- less K+ excretion, due to less Na/K ATPase

11

ENaC blockers

Prototype: amiloride, triamterene
MOA: inhibits ENaC, preventing reabsorption of Na from lumen
- diuresis, natriuresis
- less Na reabsorption --> less Na pumped from cell b Na/K ATPase
- more K+ retention

12

CA inhibitor indications

Reduce production of aqueous humor, effective for glaucoma
Increases bicarb excretion --> metabolic alkalosis
Used to treat acute mountain sickness

13

CA inhibitor SE

metabolic acidosis
Kidney stones due to alkaline urine

14

Loop diuretic indications/PK

CHF
edema
HTN

high therapeutic ceiling
Transported through organic anionic transporter (OAT) - need GFR
Other drugs can compete for OAT
Bound to albumin - reduced distribution if hypoalbuminemia
Albuminiuria can cause binding of furosemide to albumin in urine, reducing its effects
short half life

15

Loop diuretic SE

Ototoxicity
Hypokalemia
Metabolic alkalosis (loss of H+)
lose calcium/magnesium
sulfa drug

16

Thiazide diuretic indications

CHF
edema
HTN
increased Ca resorption - osteoporosis, kidney stones

17

SE of thiazides

alkalosis
hyperglycemia
hyperlipidemia
more electrolyte abnormalities than loop diuretics
ds effects: metabolic alkalosis, hypokalemia

18

Thiazides PK

narrow therapeutic range
activitiy in distal end of nephron - little chance to upregulate distal sites (changing electrolyte balance)
slow onset
when added to a full blockade of TALH (+ loop diuretic), get huge vol. of urine loss
requires GFR

19

K+ sparing diuretic indications

hypokalemia
hyperaldosteronism (spironolactone)
aldosterone-aided heart failure (spironolactone)

20

SEs of K+ sparing diuretics

hyperkalemia
metabolic acidosis
spironolactone-specific: gynocomastia, menstrual disorders, testicular atrophy