Diuretics

Question 1

Three basic renal fxns

Answer 1

filtration, reabsorption, secretion

-reabsorb substances that body needs, maintain acid-base balance, excrete waste and foreign products

Question 2

NaCl movement will result in

Answer 2

water movement- osmotic equilibrium

-increasing or decreasing Na+ reabsorption the kidney increases or decreases body fluid volume

Question 3

Diuretic drugs act by

Answer 3

blocking sodium and chloride reabsorption to inc osmotic pressure in tubules, which prevent osmotic reabsorption of water and increases urine volume

Question 4

Drugs acting early (loop diuretics) will produce

Answer 4

greatest diuresis

Question 5

Drugs acting late (potassium sparing diuretics) result in

Answer 5

weaker diuresis

Question 6

Clinical apps for diuretics

Answer 6

heart failure (loop diuretics), htn (thiazide diuretics), acute/chronic renal failure, nephrotic syndrome, cirrhosis

Question 7

Acetazolamide

Answer 7

• BlocksNaHCO3 reabsorption, and blocks Na reabsorption
• Effectiveness diminishes over several days because bicarbonate depletion enhances NaCl reabsorption
• Mainly used to treat glaucoma because ciliary body secretes bicarbonate to increase intraocular pressure– acetazolamide will decrease pressure

Question 8

Carbonic Anhydrase inhibitors

Answer 8

Act on proximal convuluted tubule
-Oral and opthalmic preparations available

Toxicities: hyperchloremic metabolic acidosis, alkalinizing urine can cause calcium phosphate salts. can cause renal potassium wasting because more Na reaches collecting duct, more K is secreted

Question 9

Sodium Glucose Cotransporter 2 (SGLT2) inhibitors

Answer 9

Not diuretics!

• 3rd line tx for type 2 DM
• Dapagliflozin, canagliflozin, empagliflozin
• Inhibits Na, Glucose reabsorption to reduce hbA1c
• Leads to weight loss

Question 10

Loop diuretics

Answer 10

Furosemide, butanemide, torsemide, ethacyrnic acid (not sulfonamide derivative)

• Inhibits Na/K/2Cl cotransporter- decreased NaCl reabsorption
• work on ascending limb of henle’s loop
• Also, additional Mg, Ca excretion because lower K potential difference cannot drive Mg and Ca to be reabsorbed paracellularly (Ca will be reabsorbed in distal tubule, but Mg will be excreted leading to hypomagnesemia)
• Most effective diuretics available
• Eliminated by tubular secretion and filtration

Question 11

Hypokalemia caused by loop diuretics

Answer 11

Inc delivery of Na to distal convoluted tubule–> enhances K and H secretion

Question 12

Loop diuretics and renin release

Answer 12

Reduced NaCl reabsorption– more Na in tubular fluid–> reduced NaCl influx into macula densa –> inc secretion of prostaglandins–> increased renin secretion (from juxtaglomerular cell)

Question 13

Clinical use of loop diuretics

Answer 13

• relief pulmonary edema
• Hypercalcemia
• htn (only if thiazides do not work)
• severe hyperkalemia (enhance K secretion)
• acute renal failure

Question 14

Loop diuretics AE

Answer 14

• ototoxicity (reversible) because Na/K/2Cl transporter in ear for transport for endolymph production in cochlea
• hyperuricemia and gout attacks- hypovolemia associated inc uric acid reabsorption in proximal tubule
• allergic reactions (more common with sulfonamides)
• hypokalemia (can lead to arrythmias)
• dehydration and hyponatremia

Question 15

Thiazide and Thiazide like diuretics

Answer 15

• names end in thiazide
• All are sulfonamides
• Inhibit Na/Cl- cotransport
• Enhanced Ca2+ reabsorption bc of inc Na gradient across basolateral membrane in distal convoluted tubule
• more effective antihtn in AA and elderly
• can lead to hyperuricemia because secreted by same system as uric acid
• inc K+ secretion in collecting duct- hypokalemia
• reduce Ca2+ excretion by enhancing reabsorption (decreased Na+ in)

Question 16

Thiazide like drugs

Answer 16

-Chlorthalidone, indapamide, metolazone, guinethazone

Question 17

Clinical uses for thiazides

Answer 17

• htn at low dose
• chf at higher dose second to loop diuretics
• nephrolithiasis for hypercalciuria
• nephrogenic diabetes insipidus to reduce polyuria and polydipsia (not known how it works bc pts already lose a lot of water)

Question 18

AE for thiazides

Answer 18

hyperuricemia, hypokalemic metabolic alkalosis, hyperglycemia, hyperlipidemia, hyponatremia

• allergic rxns- photosensitivity
• hemolytic anemia, thrombocytopenia, acute necrotizing pancreatitis
• weakness, fatigability, ED in elderly men

Question 19

Potassium sparing diuretics

Answer 19

• Act on collecting tubule
• Act on transport mechanisms that reabsorb Na (Na channel)- which is regulated by aldosterone
• high aldosterone, more Na reabsorbed, which causes K to be secreted
• both classes of drugs cause reduced K secretion
• weak diuretics, used in combination with loop or thiazide to reduce hypokalemia

Question 20

K sparing diuretics clinical uses

Answer 20

-used for chf, primary mineralocorticoid hypersecretion (ACTH), secondary aldosteronism

Question 21

aldosterone antagonists

Answer 21

• potassium sparing
• eplerenone, spironolactone
• aldosterone binds to receptors and increases Na+ reabsorption and K, H secretion– this mechanism will be blocked

Question 22

Na channel blockers

Answer 22

• potassium sparing
• Amiloride, triamterene
• block apical Na+ channels to cause loss of potential (decreases driving force for K secretion) and reduce K and H secretion

Question 23

Potassium sparing duretics toxicity

Answer 23

-hyperkalemia, hyperchloremic metabolic acidosis (H secretion reduced), gynecomastia (spironolactone), kidney stones with triamterene

Question 24

Vaptans: ADH antagonists

Answer 24

• conivaptam, tolvaptan
• ADH regulates number of aquaporins in luminal mmebrane of collecting tubule
• Dilutes urine
• vasopressin receptor antagonists
• inhibit effects of ADH
• Used to manage inappropriate ADH secretion, and added to drug regimen of CHF when ADH elevated
• Na needs to be monitored closely

Question 25

Osmotic diuretics

Answer 25

- Mannitol - Filtered by glomerulus but not reabsorbed--> inc osmolarity of ultrafiltrate and prevents water reabsorption--> promotes water diuresis - used for emergency situations- reduce intracranial pressure - IV - severe dehydration, hypernatremia, headache, nausea, vomiting

Question 26

In HF, diuretics will

Answer 26

reduce ECF volume--> reduce preload--> reduce cardiac work -first choice- furosemide (ethacrynic acid if allergic to sulfonamides) -

Question 27

Htn, diuretic use

Answer 27

Thiazides - chlorathalidone (longer 1/2 life) at low dose for htn (high dose for diuresis) - monotherapy for mild to moderate htn

Question 28

Which diuretic for GFR >30 ml/min

Answer 28

thiazide diuretics

Question 29

Which diuretic for GFR <30 ml/min

Answer 29

loop diuretics