Angina (Concepts) Flashcards Preview

Mechanism of Drug Action > Angina (Concepts) > Flashcards

Flashcards in Angina (Concepts) Deck (20)
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1
Q

What is angina pectoris?

A

Condition describing chest pain (and referred over left shoulders and upper arm) due to inadequate blood supply to the myocardium.

2
Q

Why does sympathetic stimulation reduce oxygenation of the myocardium?

A
  1. Increased heart rate, reducing duration of diastole and thus duration of myocardial perfusion.
  2. Increased force of contraction and work done by myocardium thus increasing O2 demand.
  3. Decreased efficiency of myocardium so that more O2 is used for same amount of work done.
3
Q

Why does sympathetic stimulation cause angina in individuals with atherosclerosis but not healthy individuals?

A
  1. In healthy individuals, increased O2 demand to the myocardium during sympathetic stimulation is met by arteriolar vasodilation.
  2. Atherosclerosis causes narrowing of coronary arteries so that arterioles are dilated normally to maintain adequate cardiac perfusion.
  3. During sympathetic stimulation, there is no extra capacity for increased blood supply by arteriolar vasodilation.
  4. Myocardium becomes ischaemic and causes angina.
4
Q

What changes in the myocardium occur in patients suffering from long-term angina?

A

Collateral vessels develop in coronary circulation and reduce the effects of ischaemia.

5
Q

What causes variant angina?

A

Coronary arterial spasms (unknown cause)

6
Q

What are the principles by which anti-anginal drugs function?

A
  1. Increase perfusion of myocardium
  2. Reduce O2 demand of myocardium
7
Q

What is the mechanism of action of nitrovasodilators in treating angina?

A

Organic nitrates act as substrates for eNOS, increasing production of NO, which has 3 effects:

  1. Vasodilation of coronary arteries/arterioles, increasing perfusion of myocardium.
  2. Dilation of larger muscular arteries reduces pulse wave reflection, thus reducing afterload. This reduces workload and O2 consumption of the heart.
  3. Dilation of veins reduce MSFP, reducing CVP, VR and thus preload. This reduces workload and O2 consumption of the heart.
8
Q

What is the fortuitous function of nitrovasodilators in terms of dilaton of coronary vessels?

A
  • They cause vasodilation of select collateral vessels in heart instead of general vasodilation of all vessels.
  • This allows blood to be diverted from less well perfused areas to better perfused areas.
  • General vasodilation would cause ‘coronary steal’ whereby blood is diverted away from less well perfused areas due to high resistance of narrowed vessels.
9
Q

What are the side effects of nitrovasodilators?

A
  1. Headaches: Vasodilation of cerebral vasculature
  2. Postural hypotension: Vasodilation of systemic vasculature
10
Q

What is the consequence of prolonged nitrovasodilator use?

A

Development of tolerance possibly as a result of depletion of -SH groups in body, which is required for their function.

11
Q

What is the mechanism of action of β-blockers in treating angina?

A

Reverses effects of sympathetic stimulation of increasing myocardium O2 demand.

12
Q

What is the mechanism of action of If blockers in treating angina?

A

Inhibition of If reduces heart rate which has 2 effects:

  1. Increases time spent in diastole and thus perfusion
  2. Decrease the work of the myocardium
13
Q

What type of Cav antagonists are used to treat angina and why?

A
  • Dihydropyridines
  • More selective for Cavs in VSM
14
Q

What is the mechanism of action of Cav antagonists in treating angina?

A
  1. Vasodilation in coronary vessels: Increases perfusion of the heart
  2. Vasodilation of systemic vessels: Decreases afterload and thus work of heart
15
Q

What are the contributions of the late Na+ current to angina?

A
  • Late Na+ current in cardiac myocytes increases intracellular [Na+] which decreases efficiency of NCX.
  • Causes increase in intracellular [Ca2+], which decreases the rate of relaxation of myocardium, increasing ventricular wall stiffness and end-diastolic pressure.
  • This causes increased compression of coronary vasculature, impairing perfusion of myocardium during diastole.
16
Q

What is ischaemic pre-conditioning?

A

Phenomenon whereby short periods of ischaemia protects the heart against ischaemic reperfusion injury.

17
Q

What are the mechanisms of action of KATP antagonists in preventing ischaemic reperfusion injury?

A
  1. Opening of mitoKATP channels may decrease the rate of ATP depletion within the mitochondria (possibly as a result of reduced ATP synthase activity that reverses in stoichiometry during ischaemia and causes ATP hydrolysis instead).
  2. Nicorandil may also act as NO donor and aid in NO-dependent ischaemic pre-conditioning.
  3. It may also open KATP channels in VSM cells, causing hyperpolarisation and relaxation. This leads to vasodilation and improved perfusion of myocardium.
18
Q

What are the surgical treatments for ischaemic heart disease?

A
  1. Coronary artery bypass grafting (CABG)
  2. Percutaneous coronary intervention (PCI)
19
Q

What are the problems with coronary angioplasty with insertion of stent?

A

Development of scar tissue around stent (neointimal proliferation) causing further narrowing of vessel.

20
Q

How is neointimal proliferation prevented after angioplasty?

A

Use of drug-eluting stents that inhibit cell growth