Drug Treatment of Angina Pectoris Flashcards Preview

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Flashcards in Drug Treatment of Angina Pectoris Deck (55):
1

What angina pectoris?

Chest pain due to myocardial ischaemia
Build up of metabolites (adenosine, CO2, lactate, K+ ions) activates sensory nerves
Not a disease itself

2

What is the ischaemia due to?

Increase myocardial O2 demand which is not met

3

What are the 3 types of angina?

Stable angina (most common)
Unstable angina
Variant angina (least common)

4

What is stable angina?

Attacks predictable, e.g. exercise, stress
Myocardial O2 demand not met
Involvement of chronic occlusive coronary artery disease, i.e. atherosclerosis (use of cholesterol-lowering drugs-stains)

5

What is unstable angina?

Attacks unpredictable
Coronary artery occlusion due to platelet adhesion to ruptured atherosclerotic plaque (use of anti-platelet drugs)

6

What is variant angina?

Attacks unpredictable
Coronary artery occlusion by vasospasm

7

What is dangerous in stable and unstable angina?

May cause coronary steal (where dilation can occur, this sends more blood to already well perfused areas, but where dilatation cannot occur, less blood is delivered because of the fall in input pressure)

8

What is the difference in stable and variant angina?


Stable- occulusion
Variant- spasm

9

What occurs in all forms of angina?

Decreased myocardial O2

10

How can you reduce myocardial O2 demand?

By drugs acting directly on the heart
E.g. B1-adrenoceptor blockers

11

What are B1-adrenoceptor blockers?

Competitive reversible antagonists of adrenaline and noradrenaline at cardiac beta1-adrenoceptor

12

What do B1-adrenoceptors do?

Decreases heart rate and force→ decreases myocardial work
Decrease myocardial O2 demand

13

What types of angina are B1-adrenoceptors used?

All form

14

What are the adverse effects of beta-adrenoceptor blockers in angina?

Exacerbate asthma (block of beta2-adrenoceptors in bronchi- avoid by use of alternative drug class)
Intolerance to exercise
Hyoglycaemia
Blockade of beta-adrenoceptors may uncover alpha1-mediated constriction in coronaries

15

What does Ivabradine do?

Blocks If (Na+) current that contributes to SA node depolarisation towards threshold
Sinoatrial node (where heart beat begins)
Decreases heart rate but not force
Decreases myocardial O2 demand

16

What are vasodilator drugs aiming to do to reduce myocardial O2 demand?

Dilatation of arteries
Dilatation of veins
Venous dilatation

17

How do vasodilator drugs dilate arteries?

Decreases after-load (force against which left ventricle contracts)
Decreases myocardial work
Decreases myocardial O2 demand

18

How do vasodilator drugs dilate veins?

Decreases pre-load (diastolic pressure that distends the relaxed left ventricle)

19

How do vasodilator drugs cause venous dilatation?

Decreases venous return
Decreases pre-load
Decreases stretch of ventricle and atria
Decreases strength of contraction
Decreases myocardial work
Decreases myocardial O2 demand

20

What is the Starling mechanism?

More blood, more contraction
Stretch heart further stronger contraction

21

What is the Bainbridge (atrial) reflex?

A sympathetic reflex initiated by increased blood in the atria

22

What does the bainbridge reflex cause stimulation of?

SA node
Stimulates baroreceptors in the atria causing increases SNS stimulation

23

What are nitrovasodilators?

Most commonly used anti-anginals
E.g. GTN, amyl nitrite, isosobide dinitrate, isosobide mononitrate

24

What is GTN (nitroglycerine, 10% in inert lactose base)?

Taken as sub-lingual tablet or spray
Not orally active (destroyed by first-pass metabolism)

25

How is Amyl nitrate (volatile liquid) taken?

Vials opened and inhaled
Not now used clinically but has become drug of abuse (poppers)
Both drugs rapid in onset, but action short-lived

26

What are the uses of nitrovasodilators?

Prophylaxis in stable angina (i.e. taken immediately before exercise)
Rapid relief of ongoing angina attack (all forms)

27

How are isosobide dinitrate and isosobide mononitrate taken?

Taken orally
Slower in onset and more prolonged in duration than GTN
Used for sustained prophylaxis in all forms of angina

28

What are all nitrovasodilators?

Pro drugs

29

What are nitrovasodilators?

Lipophilic- readily enter smooth muscle cells and are reduced to nitric oxide

30

What are nitrovasodilators termed?

"NO donors"

31

What do nitrovasodilators mimic?

Action of endothelium- derived NO

32

What does nitric oxide activate?

Soluble guanylate cyclase (sGC)
Cytoplasmic (soluble) enzyme

33

What does the receptor on soluble guanylate cyclase contain?

A ferrous (Fe2+) haem moiety (like O2 binding site of haemoglobin)

34

What does NO bind to?

Haem receptors

35

What does the binding of NO to haem receptors cause?

Enzyme activation
Converts GTP to cGMP
Increased cGMP causes vasodilation

36

What are anti anginal actions of nitrovasodilators?

Venous dilatation > arterial dilatation

37

What are the side effects of nitrovasodilators?

Headache (dilataton of cerebral arteries)
Tolerance on prolonged use- need drug free “washout” period to restore efficacy

38

When do L-type voltage operated calcium channels open?

Upon membrane depolarisation

39

Where does calcium enter in L-type voltage operated calcium channels?

Cardiac and vascular smooth muscle

40

What is the mechanism of L-type channel block?

Open channel block
Allosteric modulation
Tissue selectivity

41

What drugs use the open channel block mechanism?

Verapamil and diltiazem work this way

42

What is allosteric modulation?

Bind at allosteric site and reduce channel opening
Nifedipine work this way

43

What is tissue selectivity?

Smooth muscle: nifedipine > dilitiazem > verapamil
Cardiac muscle: verapamil > dilitiazem > nifedipine

44

What is the anti-anginal action of L-type blockers?

Dilate arteries (little effect on veins)
Decreases heart rate and decreases force

45

What does the dilation of arteries by L-type blockers cause?

Decreases after-load
Decreases myocardial O2 demand

46

What does the decrease in heart rate and force by L-type blockers cause?

Decreases myocardial O2 demand

47

What types of angina can L-type blockers be used in?

All forms

48

What is dilatation of coronary arteries useful for? And what it is harmful in?

Valuable in variant angina (vasospasm)
Dangerous and may cause coronary steel in stable unstable angina

49

What is vasospasm?

A condition in which an arterial spasm leads to vasoconstriction. This can lead to tissue ischemia and tissue death (necrosis).

50

What is a coronary steel?

Where an alteration of circulation patterns lead to a reduction in the blood directed to the coronary circulation.

51

What does Nifedipine cause?

Coronary steal in 10% of patients

52

What are other uses of L-type blockers?

Anti-hypertensive agents (decreases TPR; Decreases HR and decreases SV→ decrease in CO
Anti-dysrhythmic agents (Class IV)

53

What are adverse actions of L-type blockers?

Coronary steal
Headache
Constipation

54

What can occur in an extreme overdose of L-type blockers?

Heart block
Cardiac failure

55

What are the steps following the diagnosis of stable angina?

1. Short-acting nitrovasodilator (GTN) plus Beta blocker or calcium channel blocker plus drugs for secondary prevention (antiplatelet, lipid-lowering, or anti-hypertensive drugs, as appropriate)
2. Combine beta blockers and calcium channel blockers
3. Consider adding long-acting nitrovasodilator or ivabradine
4. Consider surgical intervention: stenting or coronary artery bypass grafting