Heart failure medications

Question 1

Pharmacodynamics of Digoxin

Answer 1

Inhibits Na/K ATPase
At therapeutic doses digoxin is;
- a positive inotrope
- shortens AP duration
At low doses has predominately parasympathomimetic effects

Question 2

How does Digoxin cause positive inotropy

Answer 2

Na/K ATPase inhibition increases intracellular Na.
This increase consequently reduces Ca expulsion by the Na/Ca exchanger.
The net result is increased intracellular Ca, which:
- Increases contractility
- Increases stroke volume/CO per beat
It increases ventricular excitability

Question 3

Pharmacokinetics of Digoxin

Answer 3

Bioavailability 65-80%
Large volume of distribution, widely distributed to all tissues including CNS
25% plasma protein bound
Half-life 36-40 hours in normal renal function
2/3 excreted unchanged in urine
Renal clearance is proportional to creatinine clearance

Question 4

Drugs that increase effect of Digoxin

Answer 4

Amiodarone
Macrolide antibiotics (due to increased bioavailability)
Quinidine
K depleting drugs (increases likelihood of digitalis toxicity)
Ca channel blockers

Question 5

Drugs that decreased the effect of Digoxin

Answer 5

Acid reducing agents

Question 6

What are the two mechanisms of action of furosemide

Answer 6

1. Inhibits Na/K/2Cl pump in thick ascending limb of Loop of Henle
   Decreases NaCl reabsorption
   Decreases lumen positive potential from potassium recycling, which increases Magnesium and Calcium excretion
2. Increases COX-2 and therefore prostaglandins
   Increases renal blood flow
   Subsequent increased urine output, decreases pulmonary congestion and decreases left ventricular filling pressure in congestive cardiac failure

Question 7

Pharmacokinetics of furosemide

Answer 7

Rapid absorption
Bioavailability 50%
Peak effect at 30 mins IV or 1 hour PO
95% protein bound
Urinary excretion of mostly unchanged drug
Half-life normally 1.5-2 hours, depends on renal function
Duration of action 2-3 hours

Question 8

Clinical uses of furosemide

Answer 8

Acute pulmonary oedema and other oedematous conditions
Hypertension
Hypercalcaemia
Hyperkalaemia (response enhanced by simultaneous NaCl and water administration)
Anion overdose

Question 9

Adverse effects of furosemide

Answer 9

Hypokalaemic metabolic alkalosis
Ototoxicity, usually reversible
Hypomagnesaemia
Hyperuricaemia
Allergic reactions

Question 10

Examples of aldosterone antagonists

Answer 10

spironolactone, eplerenone

Question 11

Mechanism of action spironolactone

Answer 11

Potassium sparing diuretic
Synthetic steroid
Competitive antagonist to aldosterone at the mineralocorticoid receptor
Reduces K secretion –> reduces Na absorption in collecting duct
Also inhibits H secretion

Question 12

Pharmacokinetics of spironalactone

Answer 12

Slow onset and offset of effect
Hepatic metabolism to active metabolites canrenone and 7-alpha-spirolactone (long half lives of 12-20 hours)
Duration of action 24-48 hours

Question 13

Clinical uses of spironalactone

Answer 13

Primary hyperaldosteronism
Secondary hyperaldosteronism:
CCF
Cirrhosis
Nephrotic syndrome