Pharm #6 - Diuretics

Question 1

What drugs are CA inhibitors? (4)

Answer 1

1. Acetozolamide
2. dorzolamide
3. methazolamide
4. dichlorophenamide

Question 2

MOA of CA inhibitors

Answer 2

inhibit CA in luminal membrane of PROXIMAL TUBULE

- reduce proximal HCO3- reabsorption

Question 3

Indications (main 3) of CA inhibitors

1. Acetozolamide
2. dorzolamide
3. methazolamide
4. dichlorophenamide

Answer 3

1. reduce intraocular pressure in glaucoma
2. lower HCO3- in mountain sickness
3. raise urine pH in cystinuria

OTHER:

• hypokalemic periodic paralysis
• adjunctive therapy in epilepsy
• solid hypoxic tumors

Used as a backup diuretic (weak);

Glaucoma (reduction of aqueous humor),

urinary alkalinization (to treat overdose or some kidney stones),

high-altitude sickness (dec serum pH lowers Hb affinity for O2 increasing O2 delivery to tissues)

Question 4

Side effects of CA inhibitors (2 main, 4 others)

1. Acetozolamide
2. dorzolamide
3. methazolamide
4. dichlorophenamide

Answer 4

1. Metabolic acidosis
   - due to HCO3- depletion with prolonged treatment
2. Hypokalemia (acute)
3. Drowsiness, fatigue, CNS depression, parasthesia

Question 5

What is the only osmotic diuretic

MOA

Answer 5

mannitol

• freely filterable, non-reabsorable osmotic agents like mannitol, glycerol & urea
• act primarily on the PT to reduce the reabsorption of H20 and solutes including NaCl

Question 6

Indication for mannitol

2 other uses?

Answer 6

Treat or prevent ACUTE RENAL FAILURE
(ARF)

other:

• reduce intracranial or intraocular pressure
• enhance urinary excretion of chemical toxins

Question 7

name the 4 loop diuretic

which is not a sulfa drug?

Answer 7

• furosemide
• bumetanide
• torsemide
• ethacrynic acid (not a sulfa drug)

Question 8

MOA of LOOP DIURETICS (where and what does it inhibit)

• furosemide
• bumetanide
• torsemide
• ethacrynic acid (not a sulfa drug)

Answer 8

Inhibit the Na/K/Cl cotransport system in THICK ASCENDING LIMB

Question 9

Side effects of mannitol (osmotic diuretic)

3 main (distinguish between normal and abnormal GFR changes)

Answer 9

• acute expansion of ECF volume and increased risk of pulmonary edema
• hyponatremia *with impaired renal function
• hypernatremia (prolonged use with normal GFR)
• nausea, vomiting, headache

Question 10

Indications of LOOP diuretics (6)

• furosemide
• bumetanide
• torsemide
• ethacrynic acid (not a sulfa drug)

Answer 10

1. Acute Pulmonary edema
2. CHF in presence of renal insufficiency
3. ARF,
4. CRF
5. ascites
6. nephrotic syndrome

Question 11

What drug can be used to treat hypercalcemia due to its inhibition of Calcium reabsorption?

Answer 11

LOOP DIURETICS

• furosemide
• bumetanide
• torsemide
• ethacrynic acid (not a sulfa drug)

Question 12

Adverse effects of loop diuretics

1 main, 6 others

Answer 12

1. HYPOVOLEMIA
2. Hypokalemia
3. hypomanesemia
4. Hyponatremia
5. HYPERURICEMIA
6. metabolic alkalosis
7. ototoxicity & diarrhea (mainly with ethacrynic acid)

Question 13

Which loop diuretic is mainly associated with ototoxicity and diarrhea?

Answer 13

ethacrynic acid

Question 14

State the thiazide diuretics (5)

Answer 14

1. chlorothiazide
2. hydrochlorothiazide
3. chlorthalidone
4. metolazone
5. indapamide

Question 15

1. chlorothiazide
2. hydrochlorothiazide
3. chlorthalidone
4. metolazone
5. indapamide

MOA of drug class

Answer 15

thiazide diuretics:

• inhibit NaCl cotransport in early DISTAL CONVOLUTED TUBULE (DCT)

Question 16

Indications for thiazide diuretics (5)

1. chlorothiazide
2. hydrochlorothiazide
3. chlorthalidone
4. metolazone
5. indapamide

Answer 16

1. hypertension
2. EDEMA due to CHF
3. HEPATIC CIRRHOSIS*
4. Renal disease
5. Idiopathic Hypercalciuria

Question 17

Which drug class can be used to treat idiopathic hypercalcuria? Renal caliculi

• state the drugs in this class

Answer 17

thiazide diuretics

1. chlorothiazide
2. hydrochlorothiazide
3. chlorthalidone
4. metolazone
5. indapamide

Question 18

What drug class can be used for the following:

1. Nephrogenic Diabetes Insipidus

Answer 18

THIAZIDE diuretics

• prevent further urine dilution in DCT

Question 19

Adverse affect of thiazide diuretics (6)

1. chlorothiazide
2. hydrochlorothiazide
3. chlorthalidone
4. metolazone
5. indapamide

Answer 19

1. Hypokalemia, hyonatremia, hypovolemia
2. Hyperuricemia due to increased rate reabsorption
3. hypercalcemia due to enhanced Ca reabsorption
4. metabolic alkalosis
5. hyperglycemia
6. hypersensitivity & interstitial nephritis

Question 20

What drug is contraindicated for high plasma calcium levels of primary hyperparathyroidism?

Answer 20

THIAZIDE!!!
- increase Ca reabsorption!

• use LOOP DIURETICS for hypercalcemia

Question 21

What are the 4 K+ sparing diuretics

Answer 21

1. spironolactone
2. eplerenone
3. amiloride
4. triamterene

Question 22

MOA of spironolactone and eplerenone (K+ sparing)

MOA of Amiloride and triamterene (K+ sparing)

Answer 22

• comp. block action of aldosterone on CT

- reduce Na+ entry across luminal membrane of principal cells of CT

Question 23

Indications for K+ sparing diuretics (3)

1. spironolactone
2. eplerenone
3. amiloride
4. triamterene

Answer 23

1. Chronic liver disease
   - treat secondary hyperaldosteronism due to hepatic cirrhosis complicated by ascites (spironolactone and eplerenone)
2. prevent the hypokalemic effects of other diuretics
3. Primary hyperaldosteronism (Conn’s syndrome -> spironolactone & eplerenone)

Question 24

Which drugs are used for:

1. Chronic liver disease
   - treat secondary hyperaldosteronism due to hepatic cirrhosis complicated by ascites (spironolactone and eplerenone)

Answer 24

spironolacton and eplerenone (K+ sparing and inhibit aldosterone in CT)

Question 25

``` Which drug is responsible for the following adverse effects What class of drugs do these belong to? ``` 1. HYPERKALEMIA, gynecomastia, hirsutism, mentrual irregularities, testicular atrophy 2. HYPERKALEMIA, glucose intolerance in diabetics 3. HYPERKALEMIA, megaloblastic anemia in patients with liver cirrhosis

Answer 25

K+ SPARING! 1. spironolacton: HYPERKALEMIA, gynecomastia, hirsutism, mentrual irregularities, testicular atrophy 2. Amiloride: HYPERKALEMIA, glucose intolerance in diabetics 3. triamterene: HYPERKALEMIA, megaloblastic anemia in patients with liver cirrhosis

Question 26

ADH antagonists, list the drugs (5) which blocks V1 and V2 receptors

Answer 26

1. Doxycycline 2. Lithium 3. Tolvaptan 4. conivaptan (blocks both V1 and V2 receptors) 5. Mozavaptan

Question 27

MOA of ADH antagonists - state the drugs in this class

Answer 27

- doxycycline - lithium - conivaptan - tolvaptan - mozavaptan MOA: prevent ADH induced water reabsorption in the prinicipal cells of the collecting tubule

Question 28

What drugs are indicated for the following: 1. SIADH 2. Euvolemic/hypervolemic 3. hyponatremia and CHF

Answer 28

ADH antagonists! - doxycycline - lithium - conivaptan - tolvaptan - mozavaptan

Question 29

Adverse effects of ADH antagonists: 1. lithium & doxycycline 2. tolvaptan, conivaptan, mozavaptan(5)

Answer 29

1. lithium & doxycycline: NEPHROTOXIC 2. tolvaptan, conivaptan, mozavaptan: - hypernatremia - thirst - dry mouth - hypotension* - dizziness

Question 30

Which ADH antagonists are nephrotoxic

Answer 30

lithium & doxycyline

Question 31

Which two types of drugs decrease uric acid excretion and increase net uric acid reabsorption, causing hyperurecemia and possible gout?

Answer 31

1. THIAZIDE | 2. Loop diuretics

Question 32

What drugs interact with the following: 1. ACE inhibitors 2. AG's 3. Anticoagulants

Answer 32

1. ACE inhibitors - K+ sparing diuretics (increase hyperkalemia monitor serum K+) 2. AG's - LOOP diuretics (ototoxicity & nephrotoxicity) 3. Anticoagulants - THIAZIDE AND LOOP - increased anticoagulant activity with loop - decreased anticoagulant with THIAZIDE

Question 33

Which drugs should not be used with ACE inhibitors?

Answer 33

K+ sparing diuretics!!

Question 34

Drugs ending in -amide are what type of inhibitors?

Answer 34

CA inhibitors - acetozolamide - dischorphenamide - methazolamide - dorzolamide

Question 35

What are the 2 main adverse effects of CA inhibitors?

Answer 35

1. metabolic acidosis | 2. hypokalemia

Question 36

Which drug is NOT orally absorbed and must be given via IV?

Answer 36

MANNITOL - do not give for patients with CHF or renal failure - worsens condition by pulling water out of cells into ECF!!! (also causes hyponatremia since Na follows H20 out of cells)

Question 37

which 2 drug classes are used for reduced intracranial and intraocular pressure

Answer 37

MANNITOL | CA inhibitors

Question 38

Which diuretic class is most efficacious?

Answer 38

LOOP diuretics

Question 39

State which loop diuretic is described by the following: 1. 40x more potent than furosemide & shorter half life 2. better oral absorption & LONGER half life than furosemide? 3. last resort, only used when others exhibit hypersensitivity (since it is not a sulfa drug) - nephrotoxic and ototoxic!

Answer 39

1. Bumetanide 2. Tosemide 3. ETHACRYNIC ACID

Question 40

Which drug interacts with digoxin?

Answer 40

LOOP DIURETICS -adverse effects more common in patients with hypokalemia since digoxin normally competes with K+ ions for the same binding site on Na/K ATPase

Question 41

What drug is associated with the following adverse effects: 1. hyperglycemia 2. hyperlipidemia 3. metabolic alkalosis 4. hypokalemia

Answer 41

HYDROCHLOROTHIAZIDE - thiazides make you THICK

Question 42

Which drug is: 10X more potent than Hydrochlorothiazide; most EFFICACIOUS, only one for RENAL INSUFFICIENCY!! Half-life of 4-5 hrs 1. Which thiazide has a half life of 10 -22 hrs 2. which has a half life of 44hrs? (longest)

Answer 42

METOLAZONE 1. indapamide 2. CHLORTHALIDONE is the longest

Question 43

Which drug results in increased Ca reabsorption?

Answer 43

HYDROCHLOROTHIAZIDE Hypertension Congestive heart failure Reduce Ca2+ excretion to prevent kidney stones - LOOP DIURETICS = increase CA EXCRETION! (remember test)

Question 44

Which distal nephron diuretic should be given for patients with renal insufficiency?

Answer 44

METOLAZONE

Question 45

Loop and Thiazide diuretics cause metabolic alkalosis or acidosis? Why?

Answer 45

Metabolic Alkalosis - incease Na and Cl- in tubule leads to increased lumen negative potential - lumen negative potential enhances H+ efflux from intercalated cells!

Question 46

What drug class is contraindicated for patients with the following: ``` diabetes mellitus, multiple myeloma, tubulointerstitial renal disease, and renal insufficiency on ACE inhibitors ```

Answer 46

Spironolactone, eplerenone and other K+ sparing diuretics should not be given for patients with hyperkalemia NOOOOO

Question 47

What drug can cause gynecomastia and amenorrhea? What drug can be substituted for this?

Answer 47

SPIRONOLACTONE EPLERANONE -Eplerenone is considerably more expensive than spironolactone, but it does not inhibit testosterone binding and therefore it does not induce gynecomastia or other related anti-androgenic side effects.

Question 48

How does spironolactone cause metabolic acidosis

Answer 48

***block aldosterone bindign to MR decreased Na channels & Na/K atpase = Decreased lumen negative potential (more K+ spared) Reduced driving force for H+ Decreased expression of H+ pumps

Question 49

WHAT IS THE DOC for liver cirrhosis?

Answer 49

SPIRONOLACTONE | ``` - also used for Primary hyperaldosteronism Secondary hyperaldosteronism Renin-AT system activated ```

Question 50

What drugs can exacerbate the hyperkalemia associated with AMloride?

Answer 50

NSAIDS

Question 51

Demeclocycline & Lithium are both associated with what adverse effect

Answer 51

NEPHROTOXICITY

Question 52

IV loop diuretics are used for (left/right HF) Oral Loop diuretics are used for (left/right HF)

Answer 52

1. IV = LEFT (life threatening so needs quick IV!!!) | 2. ORAL = RIGHT

Question 53

Hypernatreamia is defined as serum sodium concentration less than ____

Answer 53

136 mEq/l

Question 54

What drugs are approved for hyponatremia associated with euvolemia, hypervolemia or hypovolemia

Answer 54

AVP receptor antagonists have been shown to increase the serum [Na+] and urine output while decreasing urine osmolality. do not use furosemide! FUROSEMIDE  dramatically increases Na excretion Na sparing diuretic = VAPTANS (treat hyponatremia)

Question 55

For uncomplicated hypertension, _____ diuretic should be used in drug treatment for most, either alone or combined with drugs from other classes. This drug can also be used for what other condition?

Answer 55

thiazide - for the following conditions associated with hypertension: 2. thiazide use to reduce polyuria and increase urine osmolality in Diabetes insidious