Lecture 6.5: Drugs influencing cardiac function

Question 1

What is the function of digoxin?

Answer 1

Blocks Na-K ATPase. Results in higher background levels of Na. Because of this, another channel, the Na-Ca channel, cannot pump out Ca because it relies on a low intracellular Na concentration.

As such, increased Ca intracellularly leads to increased reuptake of Ca by the SR. The next contraction would increase Ca release, resulting in a larger contractility.

However, overuse can result in dysrrhythmias, and can alter RMP.

Question 2

How is the toxicity of digoxin increased?

Answer 2

Increased Ca, low potassium, renal impairment.

Question 3

How does stimulating SNS increase contractility? What drugs do this?

Answer 3

Stimulating SNS will prolong/increase cAMP, prolonging PKA, which results in increase of Ca influx.

Amrinone inhibits phosphodiesterase which intrinsically breaks down cAMP.

B-adrenoceptor agonists activate SNS. Dobutamine is a selective B1 agonist, so increases contractility without increasing peripheral resistance. This is also why adrenaline is better than NA.

This can increase cardiac work, a bad thing.

Question 4

What can over stimulation of SNS result in?

Answer 4

Reduced B1 expression (tolerance). Overtime, a loss of pump function.

Question 5

What are the three things we have to target in heart failure?

Answer 5

Decrease afterload, preload, increase contractility.

Question 6

How do we reduce preload?

Answer 6

Decrease blood volume via diuretics (frusemide, loop diuretic).

Dilate veins: GTN (acute).

Aldosterone receptor antagonists, such as spironolactone, inhibits aldosterone action on distal tubules, also a diuretic.

Question 7

How do we reduce afterload?

Answer 7

Arterial vasodilators (but can stimulate tachycardia).

ACE inhibitors (first line therapy) as they can inhibit cardiac remodelling, decrease constriction, decrease fluid retention. But can result in first dose hypotension.

AT1 antagonists, another alternative to ACE inhibitors.

Question 8

What is the paradox behind the use of B-adrenoceptor antagonists?

Answer 8

Decreases heart function. But despite this, it apparently increases SV, reduces afterload. Can cause hypotension, fatigue, bronchoconstriction.

Also can mask signs of hypoglycaemia, OR fake signs of it.

Examples include propranolol.