HF + anti-arrhytmics

Question 1

ACE-I - HF MOA?

Answer 1

• MOA: Inhibits Angiotensin-I (Ang-I) → Angiotensin-II (Ang-II).
  
  • Ang-II is a potent vasoconstrictor and promotes cell growth.
• The reduction in vasoconstriction reduces the after-load on the heart + improvements in left ventricular remodelling (reduced hypertrophy) reduce the pre-load.

Question 2

Aldosterone antagonists?

Answer 2

MOA: Inhibit mineralocorticoid receptors in the distal convoluted tubule of the kidney nephron = sodium and water excretion and potassium retention ∴ reduces the circulating volume.

Question 3

Beta-blockers (βBs) - MOA?

Answer 3

MOA: Reducing heart rate → reduces myocardial energy expenditure, prolongs diastolic filling time + increases coronary perfusion time.

Question 4

Digoxin

Answer 4

• Digoxin inhibits the sodium-potassium ATPase, (removes intracellular sodium in exchange for extracellular potassium).
• Inhibition of this pump causes an increase in intracellular sodium, which is subsequently removed by the sodium-calcium exchanger.
• This results in an increase in intracellular calcium, which causes an increase in contractility and cardiac output.

Question 5

Ivabradine [Chronotropic

Answer 5

Ivabradine inhibits the If (pacemaker) current in the sino-atrial node that is activated during hyperpolarisation in early diastole = a reduction in heart rate

Question 6

LOOP DIURETICS?

Answer 6

MOA: Inhibit the sodium-potassium-chloride exchanger within the loop of Henle, thereby reducing water retention. The resulting diuresis reduces blood volume.

Question 7

Neprilysin inhibitor? AND WHAT TO COMBINE WITH

Answer 7

Neprilysins = family of enzyme (metallopeptidases)= degradation of peptides including natriuretic peptides, bradykinin, + Ang-II.

natriuretic peptides = beneficial effect in HF by causing vasodilation and inhibiting the renin-angiotensin-aldosteron system (RAAS).

NOTE :combined with valsartan (an angiotensin receptor blocker, ARB)

Question 8

DRUGS = RATE/rhymn control?

Answer 8

flecainide, sotalol (beta-blocker used mainly for rhythm rather than rate control) or amiodarone are indicated.

Question 9

flecainide?

Answer 9

Use dependant NA+ channel blocker = slows conduction through HIS-purkinje system +
Reduces upstroke depolarisation.

Question 10

Sotalol?

Answer 10

Blocks flow of current through AV node and ventricles.

• Low dose beta drenergic receptor antagonisty
• Higher doses blocks voltage gated K+ channels

Question 11

amioderone - MOA?

Answer 11

Blocks voltage gated K+ channels, beta adrenergic receptors and VG-CA2+ channels.