Diuretics

Question 1

What ions are usually excreted when using a diuretic? (2) What ion may be spared?

Answer 1

Sodium, Chloride

Potassium

Question 2

Where in the nephron is majority of water, potassium and sodium reabsorbed, and urine is isoosmotic with the blood?

Answer 2

The PCT

Question 3

In what part of the nephron are organic acids actively secreted into the urine? What is the driving force for this secretion?

Answer 3

PCT

Sodium/K+ ATPase on basolateral surface

Question 4

What 2 parts of the loop of henle are urea impermeable? What part is NaCl impermeable? What part is water impermeable?

Answer 4

Urea - Descending thin, ascending thick
NaCl - Descending thin
Water - Ascending thick

Question 5

Where is the macula found? What is its function? What is the name for the phenomenon it is critical for?

Answer 5

End of thick ascending limb
Sense osmolality of urine
Tubuloglomerular feedback

Question 6

What is actively transported out of the distal convoluted tubule? Describe fluid in the DCT relative to blood [hypo, hyper, iso-tonic]? What molecules are unable to pass through DCT? (2)

Answer 6

NaCl is actively transported out of DCT
Fluid is hypotonic
Urea and Water

Question 7

The DCT is considered the [concentrating/diluting] segment of the nephron

Answer 7

Diluting

Question 8

Under what circumstance is water able to leave the collecting ducts?

Answer 8

Only is vasopressin is present

Question 9

What is the only area of the nephron that is permeable to urea?

Answer 9

The collecting ducts

Question 10

What is the vasa recta? What two molecules escape the nephron and exit via the vasa recta to return to circulation?

Answer 10

Network of blood vessels surrounding the nephron

NaCl enter vasa recta, water follows

Question 11

What is a diuretic?

Answer 11

increases solute excretion to increase the volume of urine

Question 12

What is an aquaretic?

Answer 12

Increase water but not solute excretion

Question 13

What is a natriuretic?

Answer 13

Increases excretion of sodium

Question 14

What is a saluretic?

Answer 14

Increases the excretion of sodium and chloride

Question 15

What is a kaliuretic?

Answer 15

Increases the excretion of potassium

Question 16

What are 2 conditions that diuretics are used to treat?

Answer 16

Hypertension

Edema

Question 17

What are the primary and secondary sites of action of carbonic anhydrase inhibitors?

Answer 17

Primary - PCT lumen

Secondary - distal collecting duct

Question 18

What is the major effect of carbonic anhydrase inhibitors in the nephron?

Answer 18

Cause excretion of sodium bicarbonate. Usually sodium bicarb is reabsorbed to acidify urine, blocking carbonic anhydrase prevents that process

Question 19

What is carbonic anhydrase inhibitors expected to cause? Metabolic acidosis / alkalosis?

Answer 19

They cause acidosis, so can be used to treat metabolic alkalosis

Question 20

Carbonic anhydrase inhibitors affect the secretion of the following ions: Na, K, H, HCO3 and H2PO4. Which are increased and which are decreased?

Answer 20

Na, K, HCO3 and H2PO4 increased. 
H decreased (can't acidify urine, stays in system)

Question 21

What is the example of the carbonic anhydrase inhibitor provided? Why is it regarded as a potassium wasting drug?

Answer 21

Acetazolamide

A lot of Na+ reaches the distal nephron, K+ exchanged to absorb in. Exchanged K+ is excreted

Question 22

What are 4 uses of acetazolamide?

Answer 22

Open angle glaucoma
Presurgical pressure reduction in glaucoma
Altitude sickness
Treating diuretic induced metabolic alkalosis

Question 23

What are 4 side effects of acetazolamide?

Answer 23

Metabolic acidosis
Allergy
Kidney stones
Bone marrow depression, paresthesia, tingling

Question 24

What patients should not use acetazolamide?

Answer 24

Liver cirrhosis - Renal ammonia returns to system, can worsen cirrhosis

Question 25

What is the mechanism of osmotic diuretics? What is the effect on the medullary salt gradient? What is the primary site of action in the nephron?

Answer 25

Draws water from tissues into blood, increase renal blood flow It washes out the gradient Loop of Henle

Question 26

What is the effect of osmotic diuretics on ADH activity?

Answer 26

Prevents the action of ADH (water reabsorption) because salt gradient is disrupted

Question 27

Osmotic diuretics increase the excretion of essentially all ions. What is the exception?

Answer 27

Hydrogen (acid)

Question 28

What are the 2 examples of osmotic diuretics provided?

Answer 28

Glycerin | Mannitol

Question 29

What are 4 uses of osmotic diuretics?

Answer 29

Acute renal failure Acute tubular necrosis Dialysis disequilibrium (too much solute removal) Mannitol - Reduce brain swelling before neurosurgery

Question 30

What are 3 adverse effects associated with osmotic diuretics?

Answer 30

Hyponatremia Hyponatremia and dehydration Hyperglycemia (Glycerin metabolism)

Question 31

What are 3 populations that should be cautious about using osmotic diuretics?

Answer 31

Pulmonary congestion - Can become pulmonary edema Patients with Anuria Patients with intracranial bleeding (Mannitol)

Question 32

What is the primary site of action of the loop diuretics? How do they enter the urine?

Answer 32

Thick ascending limb of loop of Henle | Organic ion transporters in proximal tubules

Question 33

What is the specific transporter inhibited by the loop diuretics? What is its effect on the medullary ion gradient? What is its effect on urine volume and concentration?

Answer 33

Na, K, Cl Symporter Diminishes the ion gradient Increases urine volume, Increased concentration

Question 34

What is the effect of loop diuretics on ion excretion? Which are spared?

Answer 34

All ion excretion is increased. None are spared

Question 35

What are the 4 examples of loop diuretics provided? Which is uniquely metabolized in the kidney (glucuronidation)?

Answer 35

Furosemide (Glucuronidation in kidney) Bumetanide Ethacrynic acid Torsemide

Question 36

Among the loop diuretics, which is also a weak carbonic anhydrase inhibitor and can increase venous capacitance? Being able to increase venous capacitance makes this drug useful for what 2 conditions?

Answer 36

Furosemide | Heart failure, pulmonary edema

Question 37

How do loop diuretics circumvent limits of salt excretion i.e. referred to as high ceiling diuretics?

Answer 37

Prevent salt transport into the macula, therefore no tubuloglomerular feed back to alter excretion rates

Question 38

What are 4 uses of loop diuretics?

Answer 38

Acute pulmonary edema Congestive heart failure Nephrotic Syndrome Edema and ascites from cirrhosis

Question 39

What class of diuretic is likely to cause hyponatremia, hypokalemia, volume depletion and metabolic alkalosis?

Answer 39

Loop diuretics

Question 40

Regarding mechanism, how thiazide diuretics work?

Answer 40

They block the sodium chloride symporter. No effect on potassium symport

Question 41

How do the thiazide diuretics get to the urine? What part of the nephron do they act on?

Answer 41

Enter urine via organic ion transporters in proximal tubule | Act in distal convoluted tubule

Question 42

What is the difference between the symporters targeted by loop diuretics and thiazide diuretics?

Answer 42

Loop - Na, Cl, K symporter | Thiazide - Na, Cl symporter

Question 43

What is the source of energy for the NaCl symporter?

Answer 43

basolateral Na+/K+ antiporter

Question 44

What is the one ion whose excretion is decreased during use of thiazide diuretics? Why?

Answer 44

Calcium excretion is decreased | Activity of the Na-Ca antiporter

Question 45

Why are thiazide diuretics not limited by tubuloglomerular feedback? What can happen to plasma calcium with prolonged use of thiazide diuretics?

Answer 45

They act distal to the macula | Plasma calcium can go up

Question 46

What are the two examples of thiazide diuretics provided? What is the example of thiazide like provided (1)?

Answer 46

Thiazide - Hydrochlorothiazide and Chlorothiazide | Thiazide like - Metolazone

Question 47

How does half life influence the use of thiazide and thiazide like diuretics?

Answer 47

Long half like (metolazone) - Hypertension | Short half life (Hydrochlorothiazide and Chlorothiazide) - acute diuresis

Question 48

What are 4 uses of thiazide diuretics?

Answer 48

Hypertension Edema from CHF Nephrogenic diabetes Calcium nephrolithiasis

Question 49

Hypotension, hypokalemia, hyponatremia, metabolic alkalosis, hypercalcemia and hyperuricemia. These are all potential side effects of _

Answer 49

Thiazide diuretics

Question 50

What patient population should not use thiazide diuretics? What drug class decreases diuretic response? What drug increases the effective dose?

Answer 50

People with sulfonamide sensitivity NSAIDs Probenecid

Question 51

What are the 2 examples of inhibitors of renal sodium channels provided? Where do the function? What is their net effect?

Answer 51

Amiloride and Triamterene Distal convoluted tubule, collecting duct Slight increase in sodium excretion, Potassium SPARING

Question 52

Renal sodium channel blockers are diuretics that decrease the secretion of most ions. What are the 2 exceptions i.e. what 2 ions are secreted more with sodium channel blockers?

Answer 52

Sodium and chloride

Question 53

Where is triamterene metabolized?

Answer 53

Liver

Question 54

What is the effect of amiloride and triamterene on potassium reabsorption?

Answer 54

Strongly increases K+ reabsorption

Question 55

How can the effects of the renal sodium channel blockers be enhanced?

Answer 55

Co-admin with loop or thiazide diuretics. This also reduces the loss of potassium

Question 56

In what sub-population are the renal sodium channels particularly effective? Why? What syndrome is it used to treat? How can it be used in cystic fibrosis

Answer 56

5% African Americans They have a mutation in ENaC beta subunit Liddle syndrome Used to clear mucus in CF patients (aerosol)

Question 57

What are 2 serious side effects of renal sodium channel blockers? What class of drug may reduce their diuretic efficiency?

Answer 57

Hyperkalemia (can lead to cardiac arrhythmia/death) Megaloblastic anemia (triamterene) NSAIDs

Question 58

What are the 2 examples of mineralocorticoid antagonists provided? How do they work? Where do they work?

Answer 58

Spironolactone and Eplerenone They antagonize the mineralocorticoid receptor (Aldosterone) Distal convoluted tubule and collecting duct

Question 59

What is they function of aldosterone? How does it work? What is a major trigger for its signalling?

Answer 59

Salt and water retention, increased secretion of K+ and protons Induces transcription of proteins that activate silent sodium channels to increase sodium retention Dehydration

Question 60

In addition to the renal sodium channel blockers, what other group of drugs are potassium sparing?

Answer 60

Mineralocorticoid receptor antagonists

Question 61

Mineralocorticoid receptor blockers are diuretics that decrease the secretion of most ions. What are the 2 exceptions i.e. what 2 ions are secreted more with mineralocorticoid receptor blockers?

Answer 61

Sodium and chloride

Question 62

To mitigate the great increase in potassium secretion by loop and thiazide diuretics, what is usually coadministered with these drug?

Answer 62

Mineralocorticoid antagonists | Renal sodium channel blockers

Question 63

What are 3 uses for spironolactone?

Answer 63

``` Primary hyperaldosteronism Secondary hyperaldosteronism (heart failure, cirrhosis, ascites, nephrotic syndrome) Ascites and edema ```

Question 64

What is the major side effect associated with the use of mineralcorticoid antagonists? What is a second concern regarding other hormones?

Answer 64

Hyperkalemia | Can cross react with other steroid receptors (feminization, menstrual irregularities)

Question 65

What class of drug decrease the diretic effect of mineralocorticoid receptor blockers

Answer 65

NSAIDs (same effect on renal sodium channel blockers)

Question 66

Because of its ability to cause diarrhea, gastritis, gastric bleeding, for what group of patients is mineralocorticoid receptor blockers contra-indicated?

Answer 66

Patients with peptic ulcers

Question 67

What is a draw back from the prolonged use of spironolactone?

Answer 67

Development of malignancies

Question 68

What are the 2 examples of antidiuretic drugs provided? How are they related?

Answer 68

Vasopressin (ADH) and Desmopressin (DDAVP) | DDAVP is synthetic analog of vasopressin

Question 69

What receptor subtypes do vasopressin and desmopressin bind?

Answer 69

Vasopressin - V1 and V2 | Desmopressin - V2 mainly

Question 70

What is arginine vasopressin?

Answer 70

Synthetic intranasal or subQ form of vasopressin

Question 71

What is the effect of activating the V1 subtype of the vasopressin receptor?

Answer 71

Reduced medullary blood flow, increased medullary salt gradient and more water reabsorption

Question 72

What is the effect of activating the V2 subtype of the vasopressin receptor? (3)

Answer 72

- More aquaporins in membrane - More urea permeability (distal duct) - Increased Na, K and Cl symporter activity (thick ascending limb)

Question 73

What is vasopressin used for?

Answer 73

Diabetes insipidus

Question 74

What are 2 side effects of vasopressin?

Answer 74

Coronary artery constriction | Water intoxication

Question 75

What is the effect of chlorpropamide?

Answer 75

Increases the secretion of ADH

Question 76

Beyond its use as a diuretic, what is another use for amiloride?

Answer 76

Used to treat lithium induced diabetes insipidus, blocks sodium channel uptake of lithium

Question 77

What causes the pain associated with gout? What are 3 drugs that can be used to treat it?

Answer 77

Presence of urate crystals in tissues and joints | Probenecid, allopurinol, colchicine

Question 78

What is the mechanism of action of allopurinol?

Answer 78

Blocks conversion of xanthine to uric acid by inhibiting xanthine oxidase

Question 79

What is the effect of colchicine?

Answer 79

Blocks neutrophil activity

Question 80

What is the biphasic effect of uricosuric agents?

Answer 80

First - decrease uric acid secretion | Second - In lumen, block uric acid reabsorption, increased excretion rate

Question 81

What are 2 major considerations / side effects of probenecid?

Answer 81

Increased risk of kidney stones | Interferes with renal excretion of several drugs (e.g. thiazide diuretics)