10 - Diuretics

Question 1

What type of reabsorption occurs in the proximal tubule? What is reabsorbed?

Answer 1

Sodium and chloride reabsorbed isosmotically: 50-70% of the filtered load.

K+ reabsorbed
Bicarb reabsorbed

Bulk of the work done in the nephron occurs here.

Question 2

Which type of diuretic can target the proximal tubule? How does it work?

Answer 2

Carbonic anhydrase inhibitors.

Question 3

What is the function of the ascending limb loop of henle? What is reabsorbed?

Answer 3

Sodium and chloride reabsorbed (20-20%): active Chloride absorbed.

Impermeable to water.

Cam compensate for increased Na+ deliver from PT by increasing reabsorption.

Question 4

What is the function of the distal tubule and collecting duct? What is reabsorbed? What controls this?

Answer 4

Sodium reabsorbed (8-9%)

Potassium secreted.

Aldosterone regulation of Na and K exchange.

Water permeability regulated by ADH (vasopressin).

Question 5

Name the renal vasodilators? What is their mechanism of action?

Answer 5

Dopamine, Fenoldapam, and atriopeptins.

Selectively dilate the renal vasculature that modifies proximal tubular function.

Increase RBF without changing GFR.

Question 6

How are renal vasodilators given? How are they used clinically?

Answer 6

Some given orally.

Used to treat hypertensive crisis and shock to provide adequate blood flow to kidneys to prevent failure.

Weak diuretic effect due to compensation occurring later in the nephron.

Question 7

What is the filtration fraction and what effect do renal vasodilators have on it?

Answer 7

Renal vasodilators decrease filtration fraction:

There’s less protein in the plasma, which causes a decrease in reabsorption. This causes more drive for water to go back into the lumen and Na will follow.

End result is increase in Na and H2O excretion (diuretic effect).

Question 8

What is an osmotic diuretic and what is its mechanism of action? What does it cause the excretion of?

Answer 8

Mannitol.

Acts on tubular lumen as a non-reabsorbable solute (ie it keeps water in the lumen and doesn’t allow reabsorption).

It increases excretion of ALL electrolytes.

Question 9

What are the uses for mannitol (osmotic diuretic)?

Answer 9

Edema, glaucoma (reduces intraocular pressure), acute renal failure.

Question 10

What is a carbonic anhydrase inhibitor and what is its mechanism of action?

Answer 10

Acetazolamide

Inhibits CA in the PT and reduces HCO2 reabsorption which alkalinizes the urine.

Question 11

How is Acetazolamide (CA inhibitor) given? What is it inhibited by?

Answer 11

Orally active; weak diuretic Inhibited by acidosis

Question 12

What are side effects of Acetazolamide? What are uses?

Answer 12

Side effects: metabolic acidosis and hypokalemia

Uses: glaucoma, alkalinize the urine to decrease drug toxicity, altitude sickness, and an anticonvulsant.

Question 13

What are the loops diuretics?

Answer 13

Furosemide, bumetanide, and Ethacrynic acid.

Question 14

What is the mechanism of action of the loop diuretics? Where does it act? What ions are impacted?

Answer 14

Inhibit Na-K-Cl symporters.

Act on cortical and medullary segments of the ascending limb of the loop of henle.

Increase the excretion of sodium, potassium, cholride, and water.

Question 15

What are disadvantages of loop diuretics?

Answer 15

Hypokalemia, alkalosis, and hypovolemia.

Question 16

What are uses of loop diuretics?

Answer 16

Edema of cardiac, hepatic, or renal origin.

Acute pulmonary edema.

HTN.

Question 17

What are the thiazide and thiazide-like diuretics? How are they given?

Answer 17

Hydrochlorothiazide and metolazone.

Orally active, intermediate efficacy, long duration of action.

Question 18

What is the mechanism of action of thiazide and thiazide-like diuretics? What effect does it have on electrolytes?

Answer 18

Inhibits Na-Cl symporter and acts on the cortical segment of the distal tubule.

Increases the excretion of sodium, potassium, chloride, and water.

Urine is hypertonic - unable to dilute.

Question 19

What effect do thiazides and thiazide-like diuretics have on potassium? What are the side effects?

Answer 19

Increase potassium secretion.

Can cause hypokalemia and alkalosis.

Question 20

What are uses of thiazide and thiazide-like diuretics?

Answer 20

Edema due to CHF, HTN, and hypercalciuria.

Question 21

What are the two types of K sparing diuretics? What drugs are examples of each?

Answer 21

Aldosterone antagonists: spironolactone and eplerenone

Sodium channel inhibitors: amiloride and triamterene

Question 22

What is the mechanism of action of potassium sparing diuretics?

Answer 22

Mineralocorticoid (aldosterone) receptor antagonists: block action of aldosterone on collecting duct

Sodium channel inhibits: block sodium entry into principal cells of collecting duct

Both increase sodium excretion and reduce potassium excretion.

Question 23

What are the disadvantages of potassium sparing diuretics such as aldosterone antagonists and sodium channel inihbitors?

Answer 23

Low efficacy (2-3% of filtered sodium load excreted).

Hyperkalemia can occur due to K sparing.

Question 24

What are uses of K sparing diuretics? Who have they been shown to be effective in?

Answer 24

Edema, HTN, seldom used alone but can be used in conjunction with a thiazide or loop diuretic to enhance natriuresis without K ions.

Aldosterone antagonists improve survival in pts with heart failure.

Question 25

Which factors are important when determining which diuretic to give a pt?

Answer 25

1. Intrinsic activity (loop>thiazide>K sparing) 2. Cost (thiazide>loop>K sparing) 3. Route of admin: IV vs. oral 4. Speed of onset: loops faster than thiazides 5. Risk to benefit ratio 6. Effects on renal hemodynamics (edema is a consequence of cardiac or hepatic disease and primary disease much be treated).

Question 26

True or false: if you keep increasing the amount of diuretic given, you will continue to improve your pts edema/condition with higher doses?

Answer 26

FALSE. There's a ceiling that can be reached for diuretic dosing at which giving a higher dose won't make any difference. Exceeding this dose can have no effect or cause adverse effects.

Question 27

Compare the ceiling effect of diuretics, what does it depend on?

Answer 27

Depends on diuretic and disease. Loop > thiazide > K sparing Diminished nephron response in nephrotic syndrome, cirrhosis, and heart failure.

Question 28

What factors contribute to edema?

Answer 28

Decreased plasma oncotic pressure: not much pulling fluid back into capillaries Increased capillary hydrostatic pressure: pushes fluid out into the interstitial space

Question 29

What is the effect of diuretic drugs in edema? Which drugs do this?

Answer 29

Increase salt and water excretion by reducing renal tubular sodium and water reabsorption. 1. reduce intravascular volume 2. reduce ECF and edema Hydrochlorothiazide, furosemide

Question 30

Describe the compartmentalization of fluids and the action of diuretics; in what order are spaces impacted by diuretics? What is the last place that fluid is drained from?

Answer 30

Diuresis first effects the vasculature, then edematous tissue, and then compartments like the peritoneum or pleural spaces. In loculated fluid ascites, fluid is mobilized slowly at a rate of 0.5 kg/d a day with diuretics.

Question 31

What are the effects of potassium imbalance? What does K loss parallel?

Answer 31

Hypokalemia rarely life-threatening, hyperkalemia can be fatal (this is why K sparing diuretics rarely given alone). K loss parallels Na excretion.

Question 32

What effect do diuretics have on acid-base balance? Which can cause metabolic acidosis, which can cause metabolic alkalosis?

Answer 32

Acidosis: CA inhibitors Alkalosis: loop diuretics and thiazide diuretics

Question 33

What effect do diuretics have in HTN? Which drugs do this?

Answer 33

Increase Na and H2O excretion by reducing renal tubular sodium and water reabsorption: 1. Lower BP 2. Prevent Na and H2O retention and enhance BP lowering by other anti-HTN drugs. Hydrochlorothiazide and furosemide

Question 34

What are the long-term effects of diuretic therapy?

Answer 34

Peripheral vascular resistance initially goes up and then later goes down, plasma volume creeps up over time, and cardiac output comes back up after initially dropping. Basically, it's complicated.

Question 35

How do diuretics have their antihypertensive effects?

Answer 35

Through vasodilation.

Question 36

What was the result of the study that looked at effects of antihypertensive drugs in pts of different races?

Answer 36

That combining Enalapril with Hydrocholorothiazide was very effective across all races in treating HTN (as opposed to either drug on its own).

Question 37

What are risk factors for heart failure?

Answer 37

``` HTN Coronary artery disease Valvular disease Obesity Diabetes Kidney disease ```

Question 38

What occurs with heart failure? What symptom is present?

Answer 38

Remodeling and ventricular enlargement occur. Increased sodium retention causing fluid overload (edema).

Question 39

What effect do diuretics have on management of chronic heart failure?

Answer 39

Reduce fluid volume and ventricular preload. Reduction in heart size improves efficiency. Reduces edema and its symptoms. Not associated with reduced mortality. (Furosemide and hydrochlorothiazide).

Question 40

What effects does AngII have on the heart?

Answer 40

Vasoconstriction(increased BP), cell growth (LVH vascular remodeling), and aldosterone production (increase in Na and H2O retention and increased BP).

Question 41

What are long term effects of Angiotensin II?

Answer 41

Cardiac fibrosis: both ventricles Left ventricular hypertrophy

Question 42

What is the vicious cycle associated with heart failure?

Answer 42

It causes a decreased CO, which increases renin and thus AngII. AngII causes vasoconstriction which increases afterload, and aldosterone which increases preload. Now the heart must work harder to overcome the vasocontriction AND aldosterne causes more volume to be brought back to the heart making it need to work even harder.

Question 43

What is the compensatory mechanism in congestive heart failure?

Answer 43

Expanded activaton of the sympathetic NS. Activation of the renin-angiotensin-aldosterone axis. Maintain perfusion of vital organs by increasing preload, stimulating contractility, and increasing arterial load.

Question 44

What are the CV actions of aldosterone?

Answer 44

Cardiac fibrosis Left ventricular hypertrophy HTN

Question 45

What improves mortality rates and reduces symptoms in pts with chronic heart failure? How do they do this?

Answer 45

Aldosterone antagonists (spironolactone and eplerenone) 1. weak diuretics have small effect on preload 2. reduce K loss and hypokalemia and enhance natriuresis due to other diuretics 3. block cardiac effects of aldosterone to decrease fibrosis, hypertrophy, and arrhythmias.