Exam 9 Diuretics Medchem Harrelson

Front 1

1. Describe how the structure of the osmotic diuretics contributes to their mechanism of action and adverse effects.

Back 1

Drug structure and nephron anatomy are important because they determine a diuretic’s site of action. To some degree, the site of action determines a diuretic’s efficacy.

1. For example, agents that work on the PCT are weak diuretics since the nephron can reabsorb a large percentage of the ions at later points in the tubule.

2. Agents like the potassium sparing diuretics are also weak diuretics because most of the glomerlular filtrate has been reabsorbed by the time it reaches their site of action (i.e., the distal tubule).

Front 2

2. Explain why the osmotic diuretics are not routinely used for hypertension.

Back 2

1. As PCT agents, the nephron can reabsorb a large percentage of the ions at later points in the tubule
2. These agents aren’t frequently used and are not the primary diuretics of choice for treating hypertension(easier to control). They are used to reduce intraocular pressure in the eye and to reduce intracranial pressure caused by cerebral edema.

Front 3

3. Describe the metabolism and uses of the osmotic diuretics.

Back 3

1. With the exception of glycerin, these agents do not undergo significant metabolism-just a bunch of solutes we dump into the renal tubule to pull water out of the bloodstream.
1. EX: mannitol is administered intravenously and due to high water solubility 80% of a dose will be eliminated in the urine within three hours.
2. The primary indication for these agents is during acute renal failure (e.g., due to severe trauma) where these drugs can help maintain urine flow. They are useful because they have rapid onset and rapid elimination

Front 4

4. Given a set of structures, what are the keys to identifying OSMOTIC DIURETICS?

Back 4

1. no S
2. lots of -OH grps (mannitol, glycerine)
3. -NH2 grps (urea)
4. estor rings + OH (isosorbide)

Front 5

5. Explain why the carbonic anhydrase inhibitors are considered weak diuretics.

Back 5

1. They act in the PCT, where the nephron can absorb a lot of the ions at later stages in the renal tubule.
2. Even though carbonic anhydrase is involved with regulating the absorption of 20 to 25% of filtered sodium there is only a small increase in the amount of sodium excreted in the urine (2 – 5%) with carbonic anhydrase inhibitors.

Front 6

6. Describe the significance of the carbonic anhydrase inhibitors with regard to the development of diuretics.

Back 6

1. Structural studies of these agents resulted in the discovery of the thiazide diuretics, which are much more effective diuretics

Front 7

7. Describe the elimination routes of thiazide diuretics.

Back 7

1. With regard to metabolism, most agents are not extensively metabolized. The are primarily excreted unchanged in the urine.

Front 8

8. Explain why potassium or magnesium supplements might be necessary when patients are using a thiazide diuretic.

Back 8

1. Thiazide diuretics can lead to electrolyte imbalances (depletion of K+/Mg2+).

Front 9

9. Given a set of structures, what are the keys to identifying thiazide diuretics

Back 9

1. NOTE: similar to carbonic anhydrase diuretics due to sulfa inclusion
2. are analogs of benzothiadiazine
3. O=S=O

Front 10

10. Explain why the high ceiling or loop diuretics are more effective at eliminating sodium ions than other types of diuretics.

Back 10

1. They work in the middle, not at the beginning or end of the renal tubule.
2. These agents work at the thick ascending loop of the Henle (i.e., loop diuretics) where they inhibit a Na+/K+/2Cl- symporter
3. Lasix = lasts six hrs

Front 11

11. Describe (pushing arrows) for the mechanism of action of ethacrynic acid and describe a type of toxicity more likely to be observed with ethacrynic acid compared to other loop diuretics. Identify a michael acceptor.

Back 11

1. Ototoxicity is more likely to be observed with ethacryic acid vs other loop diuretics.

Front 12

12. Given a set of structures, what are the keys to identifying an aldosterone receptor antagonist?

Back 12

1. steroid skeletal structure
2. pirazine/pteridine rings for amiloride and triamterene resp.

Front 13

13. Explain why spironolactone and eplerenone are potassium sparing.

Back 13

1. The binding of spironolactone to the aldosterone receptor within collecting duct cells alters aldosterone thus indirectly decreases the activity of apical ENac (epithelial Na+ channel), thereby preventing Na reabsorption and K excretion.

Front 14

14. Explain why amiloride and triamterene might be given in combination with a thiazide or loop diuretic.

Back 14

1. Hypokalemic pts.

Front 15

16. Know where different diuretics act:
PCT:
DLOH:
ALOH:
DCT:
CD:

Back 15

1. PCT: Acetazolamide, Osmotic agents
2. DLoH: Osmotic agents (mannitol)
3. ALoH: Loop agents (fuorsemide)
4. DCT: Thiazides
5. CD: Aldosterone antagonists, ADH antagonists

Front 16

17. What diuretics are most effective and why?

Back 16

1. Loop, not too soon a lg % won’t get reabsorbed at later pts in the tubule
2. Not too late  most of the glomerular filtrate has not yet been reabsorbed by the time it reaches their site of action

Front 17

Given a set of structures what are the keys to identifying THIAZIDE-LIKE diuretics?

Back 17

1. quinazoline/indole ring structs
2. Sulfur group on benzene ring

Front 18

Give the primary indication for each of these diuretics:
19. Osmotic diuretics
20. Carbonic anhydrase inh:
21. Thiazides:
22. Loops:
23. K+ sparing:

Back 18

19. Osmotic diuretics: acute renal failure, intraocular pressure
20. Carbonic anhydrase inh: intraocular pressure, struc basis for more effective diuretics (THZ’s)
21. Thiazides: 1st line for hypertension thiazide and thiazide-like diuretics
22. Loops: more edema, congestive heart failure agent
23. K+ sparing: when pt experiencing hypokalemia/hyperadolsteronism