3.2) Heart Failure

Question 1

Which 3 drug classes can induce the loss of urine?

Answer 1

-diuretic= increase production of urine
-natriuretic= loss of sodium in urine
-aquaretic= loss of water without electrolytes

Question 2

Which medical conditions are diuretics useful in treating?

Answer 2

Oedema
Primary hypertension
Heart failure
Nephrotic syndrome
CKD
Chronic liver disease

Question 3

What are some common adverse effects of diuretics?

Answer 3

Hypovolaemic and hypotension
AKI (in response to hypovolaemia- RAAS activated, when sustained causes renal injury)
Electrolyte disturbance (Na+, K+, Mg2+, Ca2+)
Metabolic abnormalities
Anaphylaxis (less common)

Question 4

Where do thiazide/thiazide-like diuretics act? Mechanism of action?

Answer 4

Inhibit Na+/Cl- co-transporter in apical membrane of distal convoluted tubule—-reduced sodium and water reabsorption.

Question 5

Adverse effects of thiazides may include?

Answer 5

Hyperuricaemia (gout)
Hyperglycaemia
Erectile dysfunction (mechanism unknown)
Increased LDL conc/ increased triglycerides
Hypercalcaemia
Hypokalaemia

Question 6

Indicate some contraindications to thiazide diuretics

Answer 6

Addison’s disease (will contribute to hyponatraemia)
Hypercalcaemia
Hyponatraemia
Refractory hypokalaemia
Symptomatic hyperuricaemia

Question 7

DDI with thiazides may include?

Answer 7

Alcohol
Amlodipine (increase risk of hypotension)

Question 8

Give examples of thiazide and thiazide like diuretics

Answer 8

Thiazide= Bendroflumethiazide
Thiazide like= indapamide

Question 9

Which type of diuretic acts on the NKCC2 transporter? Where in the nephron?

Answer 9

Loop diuretics
Acts on the thick ascending limb of the loop of henle

Question 10

Give an example of a loop diuretic

Answer 10

Furosemide
Bumetanide

Question 11

Adverse effects of loop diuretics include?

Answer 11

Dehydration
Hypotension
Hypokalaemia
Hyponatraemia
Hyperuricaemia (chronic treatment)
Arrhythmia
Tinnitus- otoxicity
Increased cholesterol and triglycerides

Question 12

Contraindications to loop diuretics?

Answer 12

Hypokalaemia
Hyponatraemia
Gout
Hepatic encephalopathy

Question 13

DDIs associated with use of loop diuretics include?

Answer 13

Aminoglycoside antibiotics ie gentamicin (increases risk of ototoxicity)
Digoxin/lithium (cause yellow/blurred vision—- excreted via kidneys therefore increased conc in plasma)

Question 14

Give an example of a drug that directly blocks ENac channels— how does this effect fluid status?

Answer 14

Amiloride— potassium sparing drug
Reduces Na+ reabsorption in DCT and reduces K+ excretion— reduces water reabsorption

Question 15

Adverse effects of amiloride?

Answer 15

Hyperkalaemia
Potential arrhythmia

Question 16

Contraindications to utilising amiloride (potassium sparing) may include?

Answer 16

Addison’s disease, anuria, hyperkalaemia

Question 17

DDIs with drugs like amiloride may include?

Answer 17

Other potassium sparing drugs (risk of hyperkalaemia)
ACEi/ARBs— reduce aldosterone therefore have same eventual effect

Question 18

What is the mechanism of action of Spironolactone or eplerenone?

Answer 18

Mineralocorticoid receptor antagonist aka aldosterone antagonist

No increased expression of ENac channels, reduced sodium reabsorption

Question 19

What is the drug class of spironolactone?

Answer 19

Potassium sparing drugs

Question 20

What are some of the possible adverse effects of Spironolactone use?

Answer 20

Gynaecomastia— (binds to androgen receptors, increases peripheral conversion of testosterone to oestradiol— proliferation of breast tissue)
Hyperkalaemia
Severe cutaneous adverse reactions

Question 21

What are some of the contraindications to using spironolactone?

Answer 21

Addison’s disease
Anuria
Hyperkalaemia

Question 22

Indicate some of the DDIs associated with Spironolactone

Answer 22

Alcohol
Amiloride (also potassium sparing, different mechanism)
ACEi
ARBs

Question 23

How do carbonic anhydrase inhibitors work?

Answer 23

Prevent absorption of HCO3- in the proximal convoluted tubule— increase urinary excretion bound to Na+

Question 24

Give an example of an osmotic agent
How does this work?

Answer 24

Mannitol
Osmotic agent draws water into the nephron lumen causing a reduced intracellular volume.

Question 25

What is the risk associated with osmotic agents?

Answer 25

Hypernatraemia risk
Concentration effect— proportional increase— increase in relative concentration of sodium ions due to loss of intracellular volume.

Question 26

Give an example of an SGLT2 inhibitor

Answer 26

Dapagliflozin

Question 27

Where do SGLT2 inhibitors work?
How do these agents work?

Answer 27

Proximal tubule
Prevent sodium and glucose from being co-transported into cells.
Prevent osmotic draw of fluid alongside reabsorption of sodium and glucose.

Question 28

How do ADH antagonists have an effect on circulating volume?

Answer 28

Diuretics not natriuretics—- inhibits inhibitor of the production of urine therefore removes inhibition.

Question 29

Examples of ADH antagonists include?

Answer 29

Tolvaptan
Lithium

Question 30

Which drinks can cause diuresis?

Answer 30

Alcohol— inhibits ADH release to allow more urine production.
Caffeine—- increases GFR and decreases tubular Na+ reabsorption- osmotic effect prevents reabsorption of water.

Question 31

What is heart failure?

Answer 31

Clinical syndrome of reduced cardiac output, tissue hypoperfusion, increased pulmonary pressures and tissue congestion.

Question 32

How do you treat heart failure?

Answer 32

1st line— diuretics
2nd line (with reduced ejection fraction)— ACEi