Pharmacotherapy of Cardiac Disease

Question 1

What are the principles of treatment for acute coronary syndromes?

Answer 1

Increase oxygen supply of the myocardium

• Increase coronary blood flow
• Give oxygen

Reduce oxygen demand of myocardium

• Reduce heart rate and contractility
• Reduce cardiac afterload
• Reduce cardiac preload

Question 2

Describe the treatment strategies for chronic heart failure

Answer 2

Improve contractility:

• Positive inotropes e.g. sympathomimetics (and modulate with beta blocker)

Reduce oedema:

• Diuretics

Reduce preload and afterload:

• ACE-Inhibitors
• Angiotensin II receptor blocker

Question 3

Why does the use of positive inotropes in heart failure often need to be modulated with a beta blocker?

Answer 3

Inotropes can cause enhanced and sustained cardiac adrenergic drive

Question 4

What are the principal targets for treatment of heart failure?

Answer 4

Heart:

• Cardiomyocytes
• Coronary arteries

Kidney:

• Renal tubular epithelial cells

Peripheral arteries:

• Vascular smooth muscle cells

Question 5

What classes of drug used for HF act directly on the heart itself?

Answer 5

ACE-inhibitors

Sympathomimetics

Inotropes

Calcium channel blockers

Beta blockers

Anticholinergics

Angiotensin receptor blockers

Aldosterone antagonists

Question 6

What classes of drugs used for HF target the kidney?

Answer 6

Diuretics

Aldosterone antagonists

ACE-inhibitors

Angiotensin II receptor blockers

Question 7

What classes of drugs used in HF act on the vascular smooth muscle cells?

Answer 7

Calcium channel blockers

ACE-inhibitors

Question 8

Describe the actions of angiotensin II on vascular smooth muscle cells

Answer 8

1. Angiotensin II binds to and activates angiotensin II receptor.
2. Angiotensin II receptor releases IP₃ which stimulates Ca²⁺ release from sarcoplasmic reticulum
3. Intracellular calcium modulated by calmodulin
4. Calcium activates myosin light chain kinase (MLCK)
5. MLCK phosphorylates myosin light chain to induce contraction.

Question 9

Describe how the stimulation of B₁ adrenoceptors in cardiac muscle drives contraction

How does this differ to the activation of B₂ adrenergic receptors in smooth muscle of the lung?

Answer 9

1. Activation of B₁ adrenoceptor activates cAMP
2. cAMP activates protein kinase A
3. Protein kinase A releases Ca²⁺ from intracellular stores
4. Increased intracellular Ca²⁺ in the cytoplasm induces muscle contraction

Opposite effects in smooth muscle- in smooth muscle protein kinase A reduces intracellular Ca²⁺ by driving it into storage therefore reducing contraction.

Question 10

Which 2 classes of drugs can be used to prevent cardiovascular disease without affecting blood pressure?

Answer 10

HMG-CoA Reductase inhibitors (Atorvastatin, Simvastatin)

Antiplatelets (Aspirin, Clopidogrel)