9. Diuretics PHARM

Question 1

what are some causes of edema?

Answer 1

heart failure, hepatic cirrhosis, renal disease, sympathetic activation, hypoalbuminemia

Question 2

how does sympathetic activation contribute to edema?

Answer 2

contributes to Na retention, vasoconstriction of the efferent arteriole (same as AtII). also, renin release via B1 receptor

Question 3

how are diuretics delivered to their site of activity? three methods

Answer 3

• glomerular filtration of drugs –> tubule
• prox tubule secretion by carriers
• reabsorption by diffusion

Question 4

why do diuretics that work more proximally have a higher max capacity?

Answer 4

more Na is absorbed proximally than distally

Question 5

Example of an osmotic diuretic? how does it work?

Answer 5

Mannitol.

filtered, but not reabsorbed. reduces tonicity of the renal medulla, decreases water reabsorption

Question 6

what are OATs?

Answer 6

organic anion transporter proteins. can carry drugs from blood into the prox tubule

Question 7

Mannitol: mechanism?

Answer 7

can pull water out of cells, into vasculature, and then diurese through kidney. contrast with albumin, which can maintain vasculature volume but cannot cause osmotic diuresis (too big to filter, stays in serum)

Question 8

mannitol: therapeutic uses?

Answer 8

glaucoma, cerebral edema

Question 9

carbonic anhydrase inhibitors: example medication?

Answer 9

acetazolamide

Question 10

CA inhibitor: location of action? mechanism?

Answer 10

prox tubule. block bicarb reabsorption, reduce Na reabsorption as a result. increase urinary excr of bicarb, Na

Question 11

CA inhibitors: why limited use/short term effect?

Answer 11

they cause metabolic acidosis (due to bicarb loss). once you have lost enough bicarb, they are less effective

Question 12

Ca inh: how do they cause hypokalemia?

Answer 12

at collecting duct, Na is reabsorbed in exchange for K – since there is more Na present, more is reabsorbed here and more K is wasted. Increased urinary K secretion/excretion.

Question 13

CA inhibitors: side effects?

Answer 13

hypoK
calcium stones due to alkalization of urine
hypersensitivity reactions due to sulfonamide residue

Question 14

Thiazide: mechanism of action

Answer 14

• inhibits NaCl symporter in distal convoluted tubule
• increases Na/Cl excretion
• blocks urinary diluting capacity
• some degree of carbonic anhydrase inhibition

Question 15

Thiazide: name of drug?

Answer 15

hydrochlorothiazide

Question 16

Thiazide: side effects? how does it cause these?

Answer 16

hypokalemia, hyponatremia
prevents reabsorption of Na at the Na/Cl symporter, so more Na arrives at the collecting duct. More is reabsorbed there so K is wasted. But overall more Na is excreted than usual.
Hypersensitivity reactions: not sure how, but know it anyway.

Question 17

Thiazide: impact on calcium?

Answer 17

can cause hyperCa. because less Na reabsorbed at distal tubule, so Ca is reab in order to maintain electroneutral cytosol

Question 18

Therapeutic uses for thiazides

Answer 18

hypertension, increasing bone density in elderly women, edema, calcium stones

Question 19

loop diuretic: prototypical drug?

Answer 19

furosemide

Question 20

loop diuretic: mechanism?

Answer 20

blocks Na-K-Cl symporter in ascending LOH
increases Na/Cl excretion
increases K excretion

Question 21

what effect do loop diuretics have on Ca and Mg excretion?

Answer 21

increase excretion of Ca, Mg due to decreased paracellular absorption in ascending limb

Question 22

what diuretic class has the highest max efficacy?

Answer 22

loop diuretics

act at the site of highest Na reabsorption

Question 23

loop diuretics: therapeutic use?

Answer 23

acute pulmonary edema
edema from other causes
HTN refractory to other diuretics

Question 24

side effects of loop diuretics?

Answer 24

volume depletion (because they are so effective)
hypoK
excess Ca and Mg excretion

Question 25

effect of loop diuretics on tubuloglomerular feedback?

Answer 25

decr Na arrival at macula densa | --> renin secretion goes up, GFR goes down because of less Na concentration at macula densa (counter to diuretic effect)

Question 26

how does furosemide travel through the bloodstream?

Answer 26

95% bound to albumin | only 5% cleared through glomerulus and available for activity

Question 27

duiretic efficacy in chronic renal insufficiency?

Answer 27

decreased renal blood flow and anionic metabolites reduce diuretic renal excretion rate, can decr concentration of drug

Question 28

diuretic efficacy in nephrotic syndrome?

Answer 28

hypoalbuminemia decr renal excretion rate

Question 29

do thiazides and loop diuretics both cause hypocalcemia?

Answer 29

no, only loop diur

Question 30

are thiazides and loop diur both uricosurics?

Answer 30

no, only loop

Question 31

do thiazides and loop diur have the same natriuretic emax?

Answer 31

no, loop are more potent

Question 32

do thiazides and loop diur both cause hypokalemia?

Answer 32

yes

Question 33

do thiazides and loop diur both decrease renin release?

Answer 33

loop diur increase renin release

Question 34

where is the location of action for K sparing diuretics?

Answer 34

the collecting duct

Question 35

how do K sparing diuretics work?

Answer 35

inhibit Na reabsorption by principal cells of late distal tubule and collecting duct decr K excretion

Question 36

which K sparing diuretic blocks the mineralocorticoid receptor?

Answer 36

spironolactone

Question 37

which K sparing diuretic blocks the ENaC?

Answer 37

amiloride

Question 38

why are K sparing diuretics used in combination with lithium?

Answer 38

to block Li uptake into principal cell, inhibit Li-induced diabetes insipidus

Question 39

what is the mechanism of the K sparing effect?

Answer 39

antagonism of mineralocorticoid receptor, blocks aldosterone effect blocks ENaC expression, insertion blocks activation of ENaC blocks Na/K ATPase expression

Question 40

what diuretic is a common add-on with heart failure patients?

Answer 40

spironolactone. showed to prolong survival

Question 41

side effects of spironolactone?

Answer 41

hyperK gynecomastia impotence

Question 42

what is the med that is an alternative to spironolactone, and does not cause gynecomastia and impotence?

Answer 42

eplerenone

Question 43

do both ENaC and MR blockers cause hyperkalemia?

Answer 43

yes

Question 44

what is the braking phenomenon?

Answer 44

diuretic resistance: decreased potency over time

Question 45

ways to manage diuretic resistance?

Answer 45

incr dose use in combination restrict fluid, Na

Question 46

what meds are used to prevent renal impairment?

Answer 46

ACE inhibitors, ARBs

Question 47

what meds are indicated for prevention of diabetic nephropathy?

Answer 47

ACE inhibitors, ARBs

Question 48

what is the mech by which ACE Inhs and ARBs prevent diabetic nephropathy?

Answer 48

selective efferent arteriolar vasodilation --> decr glo cap pressure

Question 49

treatment of central DI?

Answer 49

desmopressin. selective for V2 receptor

Question 50

what receptor does ADH use?

Answer 50

V2

Question 51

treatment of nephrogenic DI?

Answer 51

thiazides, amiloride. cannot use desmopressin because it is the ADH receptor (V2) that is the problem

Question 52

excessive vasopressin secretion leads to what?

Answer 52

hyponatremia

Question 53

morphine toxicity may occur in patients with renal impairment because morphine...

Answer 53

is converted into an active glucoronide, which is cleared by the kidney