Pharmacology: Hyperkalemia, Hypokalemia Flashcards
describe the ECG changes with hypokalemia
- flattened T waves
- ST segment depression
- prolonged QT interval
- U waves
- atrial arrhythmias
- v tach, v fib
describe the ECG changes with hyperkalemia
- tall T waves
- prolonged PR interval
- widened QRS interval
- flattened P waves
- arrhythmias – bradycardia, v tach, v fib
- sinus arrest or nodal rhythm w/ possible asystole
name the K-sparing diuretics
- triamterene, amiloride (Na channel blockers)
2. spironolactone (aldosterone agonist)
name the K-wasting diuretics
- thiazides (NaCl cotransporter blockers)
- loop diuretics (NaK2Cl cotransporter blockers)
- carbonic anhydrase inhibitors (rarely used)
- osmotic diuretics (non-reabsorbable solutes)
name the site of action:
carbonic anhydrase inhibitors
PCT
name the site of action:
osmotic diuretics
PCT, thin descending limb
name the site of action:
loop diuretics
TAL
name the site of action:
thiazide diuretics
DCT
name the site of action:
Na-channel blockers
cortical CD
name the site of action:
vaptans
CD
furosemide MOA
- 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
furosemide effects
increased excretion: Na, H2O, K, Cl, Mg, Ca
furosemide applications
- 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*)
furosemide pharmacokinetics
- 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
furosemide toxicities
- hypo: K, Na, Ca, Mg
- hypochloremic metabolic alkalosis
- ototoxicity
- sulfonamide, risk of HSN
- hyperglycemia; hyperuricemia; hyperlipidemia
sulfonamide similar to furosemide w/ longer t1/2, better oral absorption and evidence of higher effectiveness in HF
torsemide
sulfonamide similar to furosemide w/ more predictable oral absorption
bumetanide
non-sulfonamide loop diuretic
ethacrynic acid
*reserved for those w/ sulfa allergy
hydrochlorothiazide MOA
inhibits Na reabsorption in DCT via blockade NaCl cotransporter (K-wasting)
HCTZ effects
increases urinary excretion of Na and H2O; K, Mg
K-wasting
HCTZ applications
- HTN (alone, combo; not effective in pts w/ low GFR*)
- edema
- off-label: Ca nephrolithiasis, nephrogenic diabetes insipidus
HCTZ pharmacokinetics
- well absorbed via oral
- peak action 2 hrs, duration 6-12 hrs
- eliminated unchanged in urine (6-15 hr t1/2)
HCTZ toxicities
- hypo: K, Mg, Na, Ca
- orthostatic HTN
- sulfonamide
- hypochloremic metabolic alkalosis
- hyper: Ca, glycemia, uricemia
similar to HCTZ, poor oral absorption
chlorothiazide
similar to HCTZ, half-life 40-60 hrs
chlorthalidone
preferred by some HTN specialists
similar to HCTZ, long-acting and a favorite of cardiologists for adjunct diuretic in CHF
metolazone
is Mg loss greater with loop diuretics or thiazides?
- thiazides
- note: Mg primarily reabsorbed in TAL/distal nephron
in pts on thiazide diuretics, what is thought to be the primary mechanism for increased Ca reabsorption in PCT?
volume contraction
used to think it was TRPV5?
amiloride MOA
blocks ENaC channels in CD (NaK exchange; connecting tubule); K-sparing diuretic
amiloride effects
- small increase in Na excretion
- blocks major pathway for K elimination
- H, Mg and Ca excretion decreased indirectly
amiloride applications
- counteracts K loss induced by other diuretics in treatment of HTN, CHF
- off-label: ascites, pediatric HTN
amiloride pharmacokinetics
- 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
amiloride toxicities
- hyper: K (black box warning)
- hypo: Na
- hypochloremic metabolic alkalosis, hypovolemia
- dizziness, fatigue, HA
- NVD, bloating, constipation
similar to amiloride for edema and off-label for HTN, rapidly absorbed, duration of action 6-9 hrs, eliminated as drug metabolites
triamterene
spironolactone MOA
- competitive antagonist of aldosterone receptors (K-sparing, CD)
- partial agonist at androgen receptors (creates side effects)
spironolactone effects
K-sparing, blunts ability of aldosterone to promote NaK exchanged in CDs
(decreased Na entry through luminal Na channels, decreased basolateral NaK-ATPase)
spironolactone applications
- 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
spironolactone pharmacokinetics
- 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
spironolactone toxicities
- hyperkalemia
- amenorrhea, hirsutism, gynecomastia, impotence
- tumorigen in chronic animal toxicity studies
more selective aldosterone antagonist, approved for use post-MI heart failure and alone or in combo for treatment of HTN
eplerenone
what component allows licorice to potentiate aldosterone effects in the kidney? also dose-dependently increases systolic BP
glycyrrhizic acid
why must oral K be taken with water?
minimize GI irritation/laxative effect
name the drugs for treatment of hypokalemia
- KCl
- KP (hypoK and hypoP)
- KHCO3; or precursors, potassium citrate and potassium gluconate (acidosis)
what is the typical rate for IV K in hypokalemia?
10-20 mEq/hr
describe the three step treatment of hyperkalemia
- antagonize cardiac effects – IV Ca
- redistribute K into cells –
- insulin and glucose (reliable)
- B2-agonist albuterol
- bicarbonate (not recommended) - facilitate K excretion –
- K-wasting diuretic
- mineralocorticoid (if hypoaldosteronism)
- cation exchange resin
- dialysis - monitor intake <60 mEq/day; abx can be hidden source
