Diuretics DSA I

Question 1

topical ophthalmic CAIs

Answer 1

brinzolamide

dorzolamide

Question 2

diuretics

Answer 2

increase sodium excretion and amount of urine produced by kidney

Question 3

diuretic

Answer 3

increases urine volume

Question 4

natriuretic

Answer 4

increased renal sodium excretion

Question 5

K in proximal tubule

Answer 5

paracellular pathway

Question 6

HCO3 reabsorption in PCT

Answer 6

initiated by action of Na/H exchanger
-luminal membrane of proximal tubule epithelial cell

membrane and cytoplasm carbonic anhydrase catalyze
> H2CO3 to CO2 and H2O at luminal membrane
> and CO2 and H2O H2CO3 in cytoplasm

Question 7

straight segment of proximal tubule

Answer 7

acid secretory systems

-organic acids to lumen from blood

Question 8

thin descending loop

Answer 8

water reabsorption

Question 9

thin ascending loop

Answer 9

water and ion/solute impermeable

Question 10

thick ascending limb

Answer 10

Na/K/2Cl cotransporter

NKCC2 or NK2Cl

dilutes luminal fluid

Question 11

thick ascending loop potassium?

Answer 11

increased K in cell - back diffusion of K out of cell

• lumen positive charge - drive reabsorption of Mg and Ca
• paracellular pathway

Question 12

distal convoluted tubule

Answer 12

Na/Cl cotransporter
calcium channels (regulated by PTH)

Question 13

diuretic induced changes in K

Answer 13

occur in collecting tubule

Question 14

ENaC

Answer 14

Na channels in collecting tubule

-more Na to CT > more K out of cell > hypokalemia

Question 15

aldosterone

Answer 15

increases ENaC and Na/K ATPase

-more Na reabsorption and K secretion

Question 16

ADH

Answer 16

aquaporins to apical membrane in collecting tubule
-V2 receotpr

regulated by serum osmolality and volume status

Question 17

alcohol

Answer 17

decreased ADH release and increases urine production

Question 18

CAI pharmacy

Answer 18

• oral administration
• secreted prox tubule (dosing change renal insufficiency)
• no first pass
• carbonic anhydrase (-) and NHE3 (-)
• 45% bicarb reabsorption inhibited > acidosis (30 mins)
• decreased efficiency after multiple days of use

Question 19

CAI toxicity

Answer 19

• metabolic acidosis and bicarbonatirua
• renal stones - calcium salts insoluble basic pH
• hypokalemia
• drowsiness and parasthesias
• sulfa allergy

Question 20

CAI contraindications

Answer 20

-cirrhosis - decreased urine pH - less ammonia released-
>hyperammonemia and hepatic encephalopathy

-hyperchloremic acidosis or COPD
>worsen metabolic or respiratory acidosis

Question 21

CAI clinical use

Answer 21

-rarely as diuretics
-glaucoma - reduces aqueous humor formation
> decreased IOP
>topical formulations

-also used for urinary alkalinization, metabolic alkalosis, acute mountain sickness, epilepsy

Question 22

loop diuretic pharmacy

Answer 22

• oral administration
• eliminated by kidney - flitration/secretion
• half life correlates with secretion (act luminal side)
• coadmin with acids - reduced activity (same secretion)

Question 23

loop diuretic mechanism

Answer 23

(-) Na/K/2Cl cotransporter

• block Na, K, Cl, Mg, Ca transport
• induce prostaglandin synthesis
• increased K excretion

Question 24

loop diuretic toxicity

Answer 24

• overuse - hyponatremia, reduced GFR, circ collapse, thrombohemolysis, hepatic encephalopathy
• hypokalemic metabolic alkalosis (K and H loss)
• precipitate gout attacks (hyperuricemia)
• hearing loss (ototoxicity)
• sulfa allery (furosemide, bumetanide, torsemide)
• hypomagnesemia

Question 25

sulfa loop diuretics

Answer 25

furosemide, bumetanide, torsemide | -cause sulfa allergies

Question 26

contraindications for loop diuretics

Answer 26

- sulfa allergy - hepatic cirrhosis, renal failure, heart failure - postmenopause osteopenia - hypocalcemia - aminoglycoside interaction - lithium interaction - digoxin interaction

Question 27

loop diuretic drug interactions

Answer 27

aminoglycoside - ototoxicity lithium digoxin

Question 28

loop diuretics clinical use

Answer 28

- edematous states - HTN and heart failure - mild hyperkalemia - ARF - anion overdose - bromide fluoride, iodide - hypercalcemic states

Question 29

thiazide diuretics pharmacy

Answer 29

- oral admin - secreted in PCT (competes uric acid) - enhanced Ca reabsorpion (PCT volume contraction/DCT enhanced Na/Ca basolateral exchange) - weak CAI

Question 30

chlorothiazide

Answer 30

not lipid soluble - given IV

Question 31

chlorthalidone

Answer 31

long acting thiazide diuretic | -T1/2 - 47 hours

Question 32

thiazide diuretic toxicity

Answer 32

hypokalemic metabolic acidosis and hyperuricemia - decrease glucose tolerance - hyperglycemia (impaired insulin release from pancreas) - hyperlipidemia - hyponatremia - weak, fatigable, paresthesia, impotence - sulfa allergy

Question 33

contraindiciations for thiazide diuretics

Answer 33

- diabetics - efficacy reduced when NSAIDs and COX-2 inhibitors co-administered - hepatic cirrhosis, renal failure, heart failure

Question 34

thiazide diuretic clinical use

Answer 34

- HTN and heart failure - nephrolithiasis (due to hypercalciuria) - diabetes insipidus

Question 35

HCTZ in diabetes insipidus

Answer 35

nephrogenic -inhibits Na/Cl tranport in DCT > increased diuresis and reduce ECF volume > decreased GFR > tubuloglomerular feedback > less sodium and water to collecting duct (decrease urine output)

Question 36

K-sparing - MR antagonists pharmacy

Answer 36

spironolactone and eplerenone - oral admin - first pass effect - eplerenone - greater affinity for MR

Question 37

K-sparing - Na channel inhibitor pharmacy

Answer 37

amiloride and triamterene - oral admin - triamterene - first pass (give more than amiloride) - amiloride - no first pass

Question 38

K-sparing MR antagonist mechanism

Answer 38

competitive (-) of aldosterone binding to MR - decreased ENaC and Na/K ATPase activity - reduced Na reabsorption in collecting tubule - reduced K secretion****

Question 39

only diuretics not requiring access to lumen

Answer 39

MR antagonists - K sparing

Question 40

K-sparing ENaC (-)

Answer 40

block ENaC in collecting tubule | -reduced K secretion****

Question 41

K-sparing toxicity

Answer 41

hyperkalemia - increased w/ renal disease, RAAS (-), or when combined with other K-sparing diuretics - metabolic acidosis - gynecomastia, impotence, BPH (bc MR antagonists are steroids) - triamterene > kidney stones with indomethacin

Question 42

K-sparing contraindications

Answer 42

chronic renal insufficiency - use with NSAIDs, beta-blockers, ACE (-), ARB - liver disease - strong (-) of CYP3A4 - increased levels of eplerenone

Question 43

K-sparing clinical use

Answer 43

hyperaldosteronism -Conn's syndrome, heart failure, hepatic cirrhosis, nephritic -thiazides and loop diuretics can cause secondary hyperaldosteronism (use K-sparing to stop this) MR antagonists - heart failure