Diuretics

Question 1

Things reABS in PCT

Answer 1

glucose, 60-70% of Na+, NaHCO3, AA
Carbonic anhydrase must be present on the lumenal membrane for the reabsorption of HCO3
action site of acetazolamide

Question 2

Loop of Henle activities

Answer 2

H2O is lost in the descending limb into the medullary space by osmotic pull (action site of osmotic diuretics)

Ascending limp is impermeable to H2O but active NaCl reabsorption happens via Na-K-2Cl co transporter (action site of loop diuretics)

Question 3

DCT Activities

Answer 3

Impermeable to H2O.
NaCl reabs occurs via Na/Cl cotransporter.
Ca++ reabs via Na/Ca exchange on basal membrane (regulated by parathyroid hormone)

action site of Thiazide diuretics

Question 4

Collecting Tubule Activity

Answer 4

Site of regulation via aldosterone.

Weak diuretic action due to small amount of NaCl reABS here, but large role in final urinary K+, Na+ and H+ content.

Question 5

Principal Cell Activity (CT)

Answer 5

Na+ and K+ channels exist on the luminal side. driving force of Na INTO cell exceeds the force driving K OUT of a cell. SO K excretion is coupled to Na reABS

Any diuretic that increases Na delivery to this area of the nephron will enhance K excretion (K+ wasting)

Potassium SPARING diuretics act by blocking this Na+ channel (decreasing Na+ reABS) OR antagonize the aldosterone receptor

Question 6

Aldosterone activity

Answer 6

Increases number and activity of Na+ and K+ luminal channels and the Na/K pump on principal cells

Question 7

Antidiuretic hormone (CT)

Answer 7

CTs are impermeable to H2O w/o ADH (vasopressin)
When ADH is present, AQP2 (aquaporin) channels are inserted on the luminal membrane, allowing for H2O absorption

Ethanol is an ADH release inhibitor

Question 8

Thiazides MOA

Answer 8

inhibits NaCl reABS by inhibiting the Na+/Cl- cotransporter in the early segment DCT

overall effect: NaCl diuresis and decreased Ca++ excretion

Question 9

Thiazide Uses

Answer 9

Hypertension (esp. in blacks and elderly)
CHF
Hypercalcuria - reduces urinary excretion of calcium adn therefore incidence of kidney stones

Question 10

Thiazide adverse reactions

Answer 10

Hypokalemia - not advised in patients with arrhythmias, MI hx
hyperuricemia - avoid in patients with gout

Question 11

Loop of Henle Agents (high ceiling diuretics)

Answer 11

Inhibits NaCl transport via Na+/K+/2Cl- transporter in ascending loop.
Have the greatest diuretic effect due to the length of the portion of nephron they act upon
Associated w/ increase in Mg++ and Ca++ excretion.
Effects RAAS and prostaglandin systems and therefore increases renal blood flow

Question 12

Loop Diuretic Uses

Answer 12

Acute pulmonary edema - rapid reduction of extracellular fluid and venous return
Refractory edema - used if no response to Na+ restriction or thiazide diuretic
Hypercalcemia
CHF - if THZs are not strong enough in action

Question 13

Loop Diuretic Adverse Reactions

Answer 13

Hypokalemic metabolic alkalosis –> enhances secretion of K+ and H+
Ototoxicity –> esp ethacrynic acid
Hyperuricemia/hyperglycemia
hypomagnesemia
Overdose –> rapid blood volume depletion

Question 14

Potassium-Sparing Diuretic Drugs

Answer 14

Spironolactone*
Eplerenone*
Triamterene*
Amiloride*

Question 15

Loop of Henle Drugs

Answer 15

Lasix (furosemide)*
Demadex (torsemide)
Ethacrynic acid (non-sulfonamide options)

Question 16

Thiazide Duretic Drugs

Answer 16

Hydrochlorothiazide*

Chlorthalidone

Question 17

Potassium Sparing Diuretics

Answer 17

Only mild diuresis possible if used alone due to their action site - Collecting Tubules

very small NaCl rabs here, weak diuretic effect

Question 18

Spironolactone/Eplerenone

Answer 18

Competitive antagonist at the aldosterone receptor, blocks ALDO effects at collecting tubule, NOT allowing Na+ to be reabs –> lumen potential is more positive –> less K+ and H+ move into the urine

Question 19

Triamterene/Amiloride

Answer 19

Directly blocks Na+ channels on collecting duct lumen to decrease Na+ reabs. (thus decreases coupled K+ secretion)

Question 20

Spironolactone Clinical Use

Answer 20

primary hyperaldosteronism, hypokalemia, hypertension (in combo w/ thiazides), hirsutismof PCOS (blocks androgen receptor)

BOTH spironolactone and Eplerenone - CHF and HTN

Question 21

Triamterene/Amiloride Clinical Use

Answer 21

CHF and edema of secondary hyperaldosteronism

Question 22

Potassium Sparing Diuretics Adverse Reactions

Answer 22

Hyperkalemia and metabolic acidosis (H+ comes along with K+)

Spironolactone can block androgen receptor causing gynecomastia

Question 23

Carbonic Anhydrase Inhibitor Drugs

Answer 23

Acetazolamide (Diamox)

Dorzolamide (Trusopt)

Question 24

Carbonic Anhydrase Inhibitor MOA

Answer 24

Inhibition of enzyme depresses NaHCO3 reabsorption in PCT

Inhibits formation of aqueous humor that is dependent on HCO3 transport

Question 25

Carbonic Anhydrase Clinical Uses

Answer 25

major uses NOT as diuretic

Glaucoma, urinary alkalinization, chronic metabolic alkalosis, acute mountain sickness

Question 26

Osmotic Diuretic Drugs

Answer 26

Mannitol - given parenterally, poor oral absorption.

Question 27

Osmotic Diuretics MOA

Answer 27

Limits H2O reabsorption in PCT and descending LOH and CT by overcoming osmotic force for H2O to leave

DOES NOT effect Na+ reabsorption

Question 28

Osmotic Diuretics Clinical Use

Answer 28

increase urine volume in acute renal failure
Rapidly reduce ICP in head injury (decr. ECV, cant cross BBB)
acutely reduces intraoccular pressure in glaucoma

Question 29

Osmotic Diuretics Adverse reaction

Answer 29

Initial hyponatremia as an acute effect of expansion of ECV by pulling water out of cells initially

chronic use w/o water replacement can cause hypernatremia (Na+ loss in the urine is less than water loss)