A-27. Potassium excreting (wasting) diuretics

Question 1

Which solutes are reabsorbed in the Proximal Convoluted Tubules?

Answer 1

66% of sodium and potassium; 85% bicarbonate; almost all glucose and Amino Acids are reabsorbed

Question 2

In the Tall Ascending Limb how much sodium is reabsorbed?

Answer 2

20% sodium reabsorbed

Question 3

Which are the other two sites of Sodium reabsorption in the renal tubules

Answer 3

Distal Convoluted Tubule (10% Na reabs) and Collecting Tubules (3% Na reabsor)

Question 4

Classification of Diuretic Medication
3 K+ wasting diuretics
2 others

Answer 4

K+ wasting diuretics
1.) Carbonic Anhydrase inhibitors- work in PCT
2.) Loop diuretics- TAL
3.)Thiazide- DCT (main idication: hypertension, mild edemas)
Other diuretics
4.) K+-Sparing Diuretics- collecting tubules, in combo with K-wasting diuretics
5.) Osmotic Diuretics

Question 5

Carbonic anhydrase inhibitors cause

Answer 5

Bicarbonate, Na+, and H2O to be excreted causing lose of fluid and alkaline urine.
Later Na+ exchanged for K+ in collecting tubules causing hypokalemia
Also leads to more Cl- reabsorption and retention of H+ causing hypercholemic metabolic acidosis

Question 6

Carbonic anhydrase inhibitor drugs

Answer 6

Dorzolamide and Acetazolamide

Question 7

Dorzolamide used for?

Answer 7

Used topically to treat glaucoma since ciliary body normally secretes HCO3 from blood into aqueous humor

Question 8

Acetazolamide indications

Answer 8

1.) broad spectrum anti-epileptics
Slight acidosis inhibits neurons
Commonly used for women with seizures during mentruation
2.)Acute mountain sickness
-with dizziness, weakness, insomnia, HA, nausea +/- pulmonary and cerebral edema
-CA inhibition decrease CSF production and pH which increases ventilation and decreases hypoxia and symptoms
3.) Chronic metabolic alkalosis
4.)glaucoma
(idiopathic intracranial hypertension and cystine/urate stone prevention with increased urine pH)

Question 9

Side effects of Acetazolamide

Answer 9

1.) Hypercholermic metabolic acidosis with normal anion gap
2.)Hypokalemia
3.) Renal stones (Ca3(PO3)2 due to alkaline urine
(Type 2 Renal Tubular Acidosis and Hypersensitivity)

Question 10

Most effective diuretic

Answer 10

Loop Diuretics

Question 11

Where and how does loop diuretics act?

Answer 11

On the TAL (where 25% Na is reabs) by inhibiting the Na/K/2Cl cotransporter
(Does not cause an acidosis)

Question 12

What are the consequences of blocking the Na/K/2Cl cotransportor

Answer 12

• loss of water (diuresis)
• Na+ exchanged for K+ in the distal collecting tubule (hypokalemia)
• No electrochemical gradient made by K+ so Ca2+/Mg is not reabsorbed
• COX expression increases prostaglandins leading to direct vasodilation of vena cava to diminish pulmonary edema
• RBF and renin increased
• metabolic alkalosis in patient

Question 13

How is the loss of calcium later compensated by the body? Magnesium?

Answer 13

PTH allows for active reabsorption of Ca2+

Magnesium needs to be given orally

Question 14

Loop Diuretic Drugs (3)

Answer 14

Furosemide, Torsemide, and Ethacrynic Acid (not a sulfa drug)

Question 15

Indications of Loop diuretics

Answer 15

1.) Edema
2.) Hypertension
3.) Acute Renal Failure-except anuric patients
4.) Chronic Renal Failure
5.) Hypercalcemia-
6.)Intoxications (halogen/alkali metal poisoning except Li)
(Ascites?)

Question 16

Dosage of loop diuretics for Interstitial/pulmonary edema via chronic heart failure? Dosage for pulmonary edema from acute LV failure?

Answer 16

1. ) 20 mg furosemide oral daily
2. ) IV furosemide 40 mg, repeatable after half an hour acts first by dilating large veins such as vena cava, then by diuretic action)

Question 17

Drug and dosage for loop diuretic use in hypertension?

Answer 17

Torsemide 2-3 mg

Question 18

Drug and dosage for loop diuretic use in chronic renal failure?

Answer 18

Furosemide 200-2000 mg oral (binds protein so need high dosage to have effective dose)

Question 19

Contraindications for loop diuretics?

Answer 19

Cirrhosis since there is a risk of hepatic encephalopathy.
Ammonia level increases due to metabolic alkalosis in the body that inhibits ammonia transformation into ammonium.
Ammonia crosses the BBB leading to encephalopathy

Question 20

Side effects of loop diuretics

Answer 20

1. )Hypokalemia
2. ) Hypomagnesium
3. ) Metabolic alkalosis
4. ) Ototoxicity (transient deafness)
5. ) Hyperuricemia
6. ) Impaired glucose tolerance
7. ) Hyperlipidemia (increased LDL)
8. ) Interstitial Nephritis

Question 21

Metabolic alkalosis mechanism

Answer 21

Hypovolemia increases renin and aldosterone. Aldosterone causes K+ and H+ excretion; increases angiotensin II also which directly increases Na/H exchange in PCT

Question 22

Is the loop diuretic ototoxicity reversible?

Answer 22

Yes to a point, then can cause definite ototoxicity. Don’t combine with other ototoxic drugs like aminoglycosides

Question 23

How is hyperuricemia caused by loop diuretics?

Answer 23

hypovolemia associated increase of uric acid reabsorption in PCT. May cause gouty arthritis. Avoidable by starting lower doses then increasing dosage

Question 24

Impaired glucose intolerance in loop diuretics can be explained by?

Answer 24

Hypokalemia causes decreased insulin secretion and peripheral glucose uptake

Question 25

Which structural component of loop diuretics causes interstitial nephritis?

Answer 25

Sulfonamide structure of many loop diuetics leading to hypersensitivity reaction including interstitial nephritis, rash, and eosinophilia

Question 26

Loop diuretics interactions

Answer 26

NSAIDS due to COX inhibition interferes with high PGs which increases effects of loop diuretics

Question 27

K+ wasting diuretic that acts at the DCT (10% of Na)

Answer 27

Thiazide diuretics which inhibit the Na/Cl cotransporter

Question 28

Main indication of Thiazide diuretics are?

Answer 28

hypertension with moderate diuretic effect

Question 29

Typically in the DCT what ions are reabsorbed?

Answer 29

Usually a a Na/Cl cotransporter reabsorbs both and Calcium channel causes reabsorption with a basolateral Ca/Na exchange

Question 30

Less Na sodium reabsorption causes

Answer 30

osmotic diuresis and enhanced activity of basal Na/Ca exchanger (limited by PTH-regulation)

Question 31

Thiazide drugs (4)

Answer 31

Hydrochlorothiazide
Clopamide
Indapamide
Chlorthalidone

Question 32

Hydochlorothiazide 3 drug dosage and uses

Answer 32

(Diuretic use 5 mg)??
hypertension (25-100 mg)??
CHF (25-100 mg)
look at dosage list

Question 33

Indications of thiazide drugs

Answer 33

1. ) Hypertension
2. ) Edema
3. ) Idiopathic Nephrogenic Calciuria/ renal Ca stones
4. ) Osteoporosis (calcium reabsorption)
5. ) Nephrogenic DI
6. ) Heart failure

Question 34

How long til thiazide diuresis effect fades? Why

Answer 34

2-3 weeks
This is due to decrease in EC space which increases diameter of vessels, maybe due to decreased Na
Secondary decrease in Ca

Question 35

Why do thiazide drugs help in CHF? Are they used in severe hypertensive emergencies?

Answer 35

They decrease preload of heart and are NOT used in hypertensive emergencies (use loop diuretics instead)

Question 36

Mechanism of treating renal Ca stones/ Idiopathic Nephrogenic Calciuria

Answer 36

Decreased Urine Calcium via increased calcium reabsorption in DCT

Question 37

Nephrogenic DI treatment mechanism

Answer 37

Li treatment; work via hypovolemia-induced increase of Na/water reabsorption in proximal nephron
Also decreases hypertonicity of plasma which decreases thirst

Question 38

Heart failure thiazide drugs are combined with what other drugs?

Answer 38

Loop diuretics

Question 39

Side effects thiazide drugs

Answer 39

1.) Hypokalemia
2.) Metabolic Alkalosis
3.) Impaired Glucose Tolerance
4.) Acute hypouricemia (urea wasting) and chronic hyperuricemia (more transporters?)
5.) Hyperlipidemia (LDL)
(rarely hypercalcemia + Hyponatremia, more water loss + hypersensitivity since they are also sulfa drugs)

Question 40

Thiazide interations

Answer 40

Lithium causes they decrease Li renal clearance increasing risk of lithium toxicity