Heart failure treatment

Question 1

Classes of drugs for HF

Answer 1

1. positive inotropic drugs: increase HR and contractility (for late stages where pt dies without this)
   - Glycosides
   - B agonists, PDE inhibitors
2. vasodilators: reduce cardiac load for earlier stages
   - nitroprusside, nitrates
   - ACE inhibitor, AT1 blocker
3. miscellaneous
   - Diuretics
   - B blockers
   - aldosterone antagonists

Question 2

sodium nitroprusside is a

Answer 2

NO donor

Question 3

nitroprusside MOA

Answer 3

vasodilation (arterioles and veins) –> reduce cardiac load –> reduce work demand of heart

Question 4

nitroprusside PK

Answer 4

IV

can give off NO + cyanide + methemoglobin

Question 5

nitroprusside clinical uses

Answer 5

chronic or refractory HF

Question 6

nitroprusside adverse effects

Answer 6

1. hypotension
2. cyanide poisoning
3. cellular hypoxia - methemoglobin (poor O2 carrying capacity)

Question 7

What does thin descending limb of LOH do

Answer 7

reabsorption of water by osmosis

Question 8

what does thick ascending limb of LOH do

Answer 8

active reabsorption of NaCl, impermeable to water (the loop has some passive reabsorption of NaCl)
- via Na/K/2CL cotransporter on luminal membrane

• also results in K accumulation in cell –> diffusion of K back into tubular lumen –> electric potential allows reabsorption of cations like Mg and Ca via paracellular pathway

Question 9

Is DCT permeable to water

Answer 9

impermeable to water, most water reabsorption at collecting ducts

Question 10

Name 3 loop diuretics

Answer 10

sulfonamide derivatives:

furosemide, bumetanide, ethacrynic acid

Question 11

loop diuretics MOA

Answer 11

• inhibit luminal Na/K/2Cl cotransporter in thick ascending limb of LOH –> reduce Na reabsorption –> reduce water reabsorption –> reduce BV, reduce cardiac load

Question 12

which loop diuretic increases renal blood flow

Answer 12

furosemide

Question 13

what drugs interfere with loop diuretics

Answer 13

NSAIDs

- loop diuretics induce renal PG synthesis, NSAIDs reduce PG synthesis

Question 14

How do loop diuretics affect Mg and Ca

Answer 14

increase Mg and Ca excretion
- reduced absorption of K –> reduced diffusion of K back into tubular lumen –> reduce reabsorption via paracellular pathway

Question 15

loop diuretics PK

Answer 15

IV, readily absorbed, diuretic response rapid

eliminated by tubular secretion and glomerular filtration

Question 16

loop diuretics duration of action?

Answer 16

2-3 hours for furosemide

Question 17

loop diuretics clinical uses

Answer 17

1. acute PE and other edema
2. acute hyperkalemia
3. acute renal failure
4. anion overdose (due to toxic ingestion of Br, F, I)

Question 18

loop diuretics adverse effects

Answer 18

1. hypokalemic metabolic alkalosis
2. ototoxicity (cannot take with some antibiotics, eg. aminoglycosides)
3. hyperuricemia (upset of ion balance affects urea secretion)
4. hypomagnesemia (Ca not as affected as still can be reabsorbed in DCT)

Question 19

What happens at DCT (3)

Answer 19

1. electrically neutral Na/Cl cotransporter –> NaCl reabsorption
2. Ca actively reabsorbed via apical Ca channel and basolateral Na/Ca exchanger
3. PTH has (significant) influence here

Question 20

What are thiazides

Answer 20

diuretics that work at DCT

Question 21

Name 3 thiazides

Answer 21

hydrochlorothiazide, indapamide, chlorthalidone

Question 22

Thiazide MOA

Answer 22

inhibit Na/Cl cotransporter on apical surface of DCT –> inhibit NaCl reabsorption –> reduce water reabsorption –> reduce BV, reduce cardiac load

Question 23

Thiazide effect on Ca

Answer 23

enhance Ca absorption (due to reduced intracellular Na)

Question 24

What drug affects thiazides

Answer 24

NSAIDs (reduce PG synthesis which is needed for thiazide action)

Question 25

thiazide clinical uses

Answer 25

1. hypertension 2. CHF 3. nephrolithiasis due to idiopathic hypercalciuria 4. nephrogenic diabetes insipidus

Question 26

thiazide adverse effects

Answer 26

1. hypokalemic metabolic alkalosis 2. hyperuricemia 3. hyperglycemia, hyperlipidemia 4. hyponatremia

Question 27

what happens at collecting tubule (3)

Answer 27

1. final site of NaCl reabsorption --> determines final conc of NaCl --> determines water reabsorption 2. site of K secretion 3. mineralocorticoids have significant influence here

Question 28

cells at collecting tubule

Answer 28

Principle cells: - reabsorption of Na coupled to secretion of K - regulated by aldosterone - water permeability increased by ADH induced fusion of vesicles containing preformed water channels with apical membranes Intercalated cells: - proton secretion

Question 29

Name 4 potassium sparing diuretics

Answer 29

spironolactone, triamterene, amiloride, eplerenone

Question 30

potassium sparing diuretics MOA

Answer 30

Act at collecting tubule - spironolactone, eplerenone: inhibit aldosterone receptor --> inhibit Na channel - triamterene, amiloride: inhibit Na channel => reduce Na reabsorption, reduce K secretion

Question 31

which potassium sparing diuretic has slow onset of action

Answer 31

spironolactone | - need time for product of genes that have their expression upregulated by aldosterone to get degraded

Question 32

why is triamterene given more frequently than amiloride

Answer 32

triamterene is metabolised in liver and has shroter half life

Question 33

how is amiloride excreted

Answer 33

excreted unchanged in urine

Question 34

which potassium sparing diuretic is excreted unchanged in urine

Answer 34

amiloride

Question 35

potassium sparing diuretics clinical uses

Answer 35

1. diuretic (CHF, hypertension, etc.) | 2. hyperaldosteronism

Question 36

potassium sparing diuretics adverse effects

Answer 36

1. hyperkalemic metabolic acidosis 2. gynecomastia (except eplerenone) 3. acute renal failure (esp triamterene + indomethacin) 4. kidney stones (for triamterene)

Question 37

which potassium sparing diuretics causes kidney stones

Answer 37

triamterene

Question 38

which potassium sparing diuretic when used with indomethacin causes acute renal failure

Answer 38

triamterene

Question 39

general contraindications

Answer 39

CHF: Ca channel blockers cannot Asthma: B blockers (esp non selective) cannot Diabetes: B blockers (masks symptoms of hypoglycemia) Pregnancy: ACEI/AT1 blocker (affect fetus renal function)