Diuretics/potassium Supplements

Front 1

How do most diuretics work and what is the renal response?

Back 1

Most diurectics work by decreaed total body NaCl content, thus decreasing extracellular water.

Renal response: Diuretic braking (occurs w/ continued administration). Mechanisms include:
Activation of SNS
Activation of RAAS
Decreased arterial BP, reduces pressire Na uresis
Hypertrophy Renal epithelial cells
Increased expression of transporter genes
Alterations in ANP

Front 2

5 Classes of Diuretics?

Back 2

Osmotic Diuretics
Carbonic anhydrase inhibitors
Thiazide diuretics
Loop diuretics
Potassium Sparing Diuretcs

Front 3

What are the two Thiazide diuretics that do not end in -thiazide?

Back 3

Indapamide and Metolazone (these two work in renal failure)

Front 4

Thiazide mechanism of action

Back 4

Inhibit NaCl transport in early distal convoluted tubule (inhibit a NaCl symporter).

Thiazide diuretics are not effective in decreased renal function because they must be secreted into tubular side for effect.

Front 5

Which diuretic is most useful for treatment of recurrent Ca stones?

Do thiazides causes reduction in BV or vascular resistance?

Do they have maximal effects on BP below maximal diuretic dosage?

Do they elevate plasma uric acid/triglyceride levels?

Do they cause Ototoxicity?

Back 5

Thiazides
Yes
Yes
Yes
NO (loop diuretics do)

Front 6

List thiazide effects on Urinary Excretion.

Back 6

Increased excretion of Na and Cl. Hyperosmolar urine.

Loss of K (more K exchanged for Na).

Decreased urinary Calcium Excretion (increase Na-Ca exchange causing lower Urinary Ca concentration).

Uric acid Excretion (increased via acute admin, decreased via chronic)

Magnesium Deficiency

Reduced Peripheral Vascular Resistance (decreased BP due to decreased BV causing decreased CO)

Front 7

What is the major use of Thiazide diuretics?

Back 7

Decrease Peripheral Vascular Resistance.

Front 8

Thiazide Diuretic uses:

Back 8

HTN (can be maintained for years), Edema via CHF, Renal Edema (initial Tx is Loop diuretic, if fails give Metolazone w/ Loop), Hypercalciurua, Nephrogenic Diabetes Insipidus (no response for ADH in this disease, Thiazides substitute for ADH).

Front 9

How long does it take to see a reduction in BP w/ thiazide diuretics?

Back 9

1 - 3 weeks

Front 10

Adverse Effects of Thiazide Diuretics

Back 10

Hypokalemia (most frequent problem, predisposes digitalis pt's to Ventricular Arrhythmias)
Hyperruricemia (can cause gout)
Volume depletion
Hypercalcemia
Hyperglycemia
Electrolyte imbalances
**Thiazides are sulfonamides that share sulfonamide allergenictiy.

Front 11

Metolazone

Back 11

Thiazide diuretic for management of edema/HTN. Safe for use w/ impaired renal function.

Front 12

Indapamide

Back 12

Thiazide diuretic used as oral antihypertensive/diuretic. Half-life 10-22 hrs. Indapamide is less likely to accumulate in pt's w/ renal failure and may be useful in their treatment.

Front 13

Carbonic Anhydrase Inhibitors mentioned?

Back 13

Acetazolamide, Dichlorphenamide, Methazolamide, Dorzolamide.

Front 14

Mechanism for Carbonic Anhydrase Inhibitors?

Back 14

Carbonic Anyhraseis located in the proximal tubule and acts in Bicarbonate resorption.

Inhibition results in decreased Na/H exchange causing mild diuresis. Also causes an elevation in urinary pH and can cause a hyperchloremic metablolic acidosis

Front 15

Therapeutic Uses of Carbonic Anhydrase inhibitors

Back 15

Treatment of HF (use loops/thiazides)
**Acetazolamide reduces high intraocular pressure in open angle glaucoma.
Epilepsy
Acute mountain sickness (prophylaxis better)
Familial Hypokalemic Periodic paralysis
**Dorzolamide used for Glaucoma/Ocular HTN
***Methazolamide:gluacoma

Front 16

What are the adverse effects of Carbonic Anhydrase Inhibitors?

Back 16

Metabolic Acidosis. Hepatic Encephalopath in pt's w/ cirrhosis? Allergy, skin toxicity, bone-marrow depression (sulfonamides)

Front 17

What are the loop diuretics mentioned?

Back 17

Bumetanide, Furosemide, Torsemide, Ethacrynic Acid (E.A does not contain sulfur, very toxic)

Front 18

Mechanism of action of Loop Diuretics

Back 18

Loop diuretics act in the Ascending Loop of Henle and inhibit a couple Na/K/2Cl symport. Loop diuretics are the most efficacious diuretic drugs.

Front 19

What effect do Loop diuretics and Thiazide diuretics have on Caclium levels in Urine?

Back 19

Thiazide diuretics decrease Ca content in urine

Loop Diuretics increase Ca content in urine

Front 20

What effect do loop diuretics have on Uric Acid excretion?

Back 20

Acutely: increase uric acid excretion

Chronicly: decrease Uric acid excretion

Front 21

Uses of Loop Diuretics:

Back 21

**Drugs of choice in Acute Pulmonary Edema of CHF
Treatment of Hypercalcemia
HTN when other drugs don't work
**Edema of Nephrotic Syndrome, only Loop diuretics work
Edema of Cirrhosis

Front 22

What are the adverse effects of Loop Diuretics?

Back 22

Abnormalities in fluid/electrolytes
Ototoxicity (Ethacrynic acid!, specially w/ Aminoglycosides)
Hyperuricemia: (cause gouty attacks)
Acute hypovolemia:
Increase LDL
Skin rashes/photosensitivity/bone marrow depression
Potassium Depletion (increased exchange of Na for K, loss of K results in hypokalemic alkalosis)

Loop Diuretics have many drug interactions

Front 23

Bumetanide

Back 23

used in management of edema due to CHF, cirrhosis, renal disease.

Loop Diuretic

Front 24

Torsemide:

Back 24

Oral/IV. Longer duration of action w/ 24 hr dosing

loop diuretic

Front 25

List the potassium sparing diuretics

Back 25

Triamterene, Amiloride, and Spironolactone (inhibits aldosterone) [eplerenone is in same class as spironolactone]

Front 26

Mechanism for Triamteren and Amiloride

Back 26

Potassium Sparing DIuretics

Block Na channels in late distal tubule/collecting duct which decreases K excretion. Action does not depend on Aldosterone and works in Addison's disease.

Not very good diuretics, used in combo's

Front 27

Side effects of Triamteren and Amiloride

Back 27

Leg cramps, increased BUN, uric acid/K retention.

Front 28

Action/Mech of Spironolactone

Back 28

Anatgonize aldosterone in cortical collecting tubule and late distal tubule. Inhibits Na reabsorption, K and H secretion.

Major use: HTN in combo w/ thiazide.

Front 29

Does Spironolcatione work in pt's w/ Addison's disease?

Back 29

No, w/ no aldosterone circulatin no diuretic effects will be seen.

Front 30

Uses if spironolactone

Back 30

Diuretic: given w/ thiazide/loop diuretic.
Primary Hyperaldosteronism: Conn's syndrome
Secondary Hyperaldosteronism
Severe Heart Failure
Hepatic Cirrhosis

Front 31

Adverse effects of spironolactone

Back 31

Life threatening Hyperkalemia. Gynecomastia, menstrual irregularites.

Front 32

Osmotic Diuretics mentioned in class

Back 32

Mannitol, Sorbitol, Glycerin, Isosorbide, urea

Front 33

Which agent is used in pt's w/ cerebra edema?

Back 33

Osmotic Agent (mannitol)

Front 34

Mechanism of action

Back 34

Limited resorption in kidney causing increased diuretics. Major site of action Loop of Henle. Not useful in pt's w/ increased Na Retention. Can given Urea for Glaucoma.

Front 35

Side effects of Osmotic Diuretics/

Back 35

Headache, Blurred Vision