Pharmacology: Hyperkalemia, Hypokalemia

Question 1

describe the ECG changes with hypokalemia

Answer 1

1. flattened T waves
2. ST segment depression
3. prolonged QT interval
4. U waves
5. atrial arrhythmias
6. v tach, v fib

Question 2

describe the ECG changes with hyperkalemia

Answer 2

1. tall T waves
2. prolonged PR interval
3. widened QRS interval
4. flattened P waves
5. arrhythmias – bradycardia, v tach, v fib
6. sinus arrest or nodal rhythm w/ possible asystole

Question 3

name the K-sparing diuretics

Answer 3

1. triamterene, amiloride (Na channel blockers)

2. spironolactone (aldosterone agonist)

Question 4

name the K-wasting diuretics

Answer 4

1. thiazides (NaCl cotransporter blockers)
2. loop diuretics (NaK2Cl cotransporter blockers)
3. carbonic anhydrase inhibitors (rarely used)
4. osmotic diuretics (non-reabsorbable solutes)

Question 5

name the site of action:

carbonic anhydrase inhibitors

Answer 5

PCT

Question 6

name the site of action:

osmotic diuretics

Answer 6

PCT, thin descending limb

Question 7

name the site of action:

loop diuretics

Answer 7

TAL

Question 8

name the site of action:

thiazide diuretics

Answer 8

DCT

Question 9

name the site of action:

Na-channel blockers

Answer 9

cortical CD

Question 10

name the site of action:

vaptans

Answer 10

CD

Question 11

furosemide MOA

Answer 11

• directly inhibits reabsorption of Na and Cl in TAL via blocking NaK2Cl cotransporter (loop diuretic; K-wasting)
• indirectly inhibits paracellular reabsorption of Ca and Mg by TAL d/t loss of K backleak responsible for lumen + transepithelial potential

Question 12

furosemide effects

Answer 12

increased excretion: Na, H2O, K, Cl, Mg, Ca

Question 13

furosemide applications

Answer 13

• edema from CHF, hepatic disease, renal disease
• acute pulmonary edema (decrease preload; rapid dyspnea relief)
• HTN (alone or combo; will work in pts w/ low GFR*)

Question 14

furosemide pharmacokinetics

Answer 14

• onset: IV ~5 mins, PO and IM 30 mins
• duration: 6-8 hrs oral, 2 hrs IV
• half life: ~0.5-2 hrs, longer if low GFR
• eliminated unchanged in urine

Question 15

furosemide toxicities

Answer 15

• hypo: K, Na, Ca, Mg
• hypochloremic metabolic alkalosis
• ototoxicity
• sulfonamide, risk of HSN
• hyperglycemia; hyperuricemia; hyperlipidemia

Question 16

sulfonamide similar to furosemide w/ longer t1/2, better oral absorption and evidence of higher effectiveness in HF

Answer 16

torsemide

Question 17

sulfonamide similar to furosemide w/ more predictable oral absorption

Answer 17

bumetanide

Question 18

non-sulfonamide loop diuretic

Answer 18

ethacrynic acid

*reserved for those w/ sulfa allergy

Question 19

hydrochlorothiazide MOA

Answer 19

inhibits Na reabsorption in DCT via blockade NaCl cotransporter (K-wasting)

Question 20

HCTZ effects

Answer 20

increases urinary excretion of Na and H2O; K, Mg

K-wasting

Question 21

HCTZ applications

Answer 21

• HTN (alone, combo; not effective in pts w/ low GFR*)
• edema
• off-label: Ca nephrolithiasis, nephrogenic diabetes insipidus

Question 22

HCTZ pharmacokinetics

Answer 22

• well absorbed via oral
• peak action 2 hrs, duration 6-12 hrs
• eliminated unchanged in urine (6-15 hr t1/2)

Question 23

HCTZ toxicities

Answer 23

• hypo: K, Mg, Na, Ca
• orthostatic HTN
• sulfonamide
• hypochloremic metabolic alkalosis
• hyper: Ca, glycemia, uricemia

Question 24

similar to HCTZ, poor oral absorption

Answer 24

chlorothiazide

Question 25

similar to HCTZ, half-life 40-60 hrs

Answer 25

chlorthalidone preferred by some HTN specialists

Question 26

similar to HCTZ, long-acting and a favorite of cardiologists for adjunct diuretic in CHF

Answer 26

metolazone

Question 27

is Mg loss greater with loop diuretics or thiazides?

Answer 27

- thiazides | - note: Mg primarily reabsorbed in TAL/distal nephron

Question 28

in pts on thiazide diuretics, what is thought to be the primary mechanism for increased Ca reabsorption in PCT?

Answer 28

volume contraction used to think it was TRPV5?

Question 29

amiloride MOA

Answer 29

blocks ENaC channels in CD (NaK exchange; connecting tubule); K-sparing diuretic

Question 30

amiloride effects

Answer 30

- small increase in Na excretion - blocks major pathway for K elimination - H, Mg and Ca excretion decreased indirectly

Question 31

amiloride applications

Answer 31

- counteracts K loss induced by other diuretics in treatment of HTN, CHF - off-label: ascites, pediatric HTN

Question 32

amiloride pharmacokinetics

Answer 32

- oral, onset <2 hrs but small effects - t1/2 6-9 hrs, increased w/ low GFR - excreted unchanged in urine and feces - DDI: enhancing effects of other K-sparing drugs (ACEi, ARB) and exacerbating hypotensive effects

Question 33

amiloride toxicities

Answer 33

- hyper: K (black box warning) - hypo: Na - hypochloremic metabolic alkalosis, hypovolemia - dizziness, fatigue, HA - NVD, bloating, constipation

Question 34

similar to amiloride for edema and off-label for HTN, rapidly absorbed, duration of action 6-9 hrs, eliminated as drug metabolites

Answer 34

triamterene

Question 35

spironolactone MOA

Answer 35

- competitive antagonist of aldosterone receptors (K-sparing, CD) - partial agonist at androgen receptors (creates side effects)

Question 36

spironolactone effects

Answer 36

K-sparing, blunts ability of aldosterone to promote NaK exchanged in CDs (decreased Na entry through luminal Na channels, decreased basolateral NaK-ATPase)

Question 37

spironolactone applications

Answer 37

- counteracts K loss induced by other diuretics in treatment of HTN, CHF, ascites - treatment of primary hyperaldosteronism (Conn) - **off-label: reduce fibrosis post-MI heart failure** - off-label: hirsutism, treatment of androgenic alopecia in females

Question 38

spironolactone pharmacokinetics

Answer 38

- t1/2 ~20 hrs - steroid effects slow on and slow off, single dose lasts 2-3 days - DDIs: enhancing effects of K-sparing drugs (ACEi, ARB) and exacerbating hypotensive effects of others

Question 39

spironolactone toxicities

Answer 39

- hyperkalemia - amenorrhea, hirsutism, gynecomastia, impotence - tumorigen in chronic animal toxicity studies

Question 40

more selective aldosterone antagonist, approved for use post-MI heart failure and alone or in combo for treatment of HTN

Answer 40

eplerenone

Question 41

what component allows licorice to potentiate aldosterone effects in the kidney? also dose-dependently increases systolic BP

Answer 41

glycyrrhizic acid

Question 42

why must oral K be taken with water?

Answer 42

minimize GI irritation/laxative effect

Question 43

name the drugs for treatment of hypokalemia

Answer 43

- KCl - KP (hypoK and hypoP) - KHCO3; or precursors, potassium citrate and potassium gluconate (acidosis)

Question 44

what is the typical rate for IV K in hypokalemia?

Answer 44

10-20 mEq/hr

Question 45

describe the three step treatment of hyperkalemia

Answer 45

1. antagonize cardiac effects -- IV Ca 2. redistribute K into cells -- - insulin and glucose (reliable) - B2-agonist albuterol - bicarbonate (not recommended) 3. facilitate K excretion -- - K-wasting diuretic - mineralocorticoid (if hypoaldosteronism) - cation exchange resin - dialysis 4. monitor intake <60 mEq/day; abx can be hidden source