Drug Treatment of Angina Pectoris

Question 1

What angina pectoris?

Answer 1

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

Question 2

What is the ischaemia due to?

Answer 2

Increase myocardial O2 demand which is not met

Question 3

What are the 3 types of angina?

Answer 3

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

Question 4

What is stable angina?

Answer 4

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)

Question 5

What is unstable angina?

Answer 5

Attacks unpredictable

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

Question 6

What is variant angina?

Answer 6

Attacks unpredictable

Coronary artery occlusion by vasospasm

Question 7

What is dangerous in stable and unstable angina?

Answer 7

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)

Question 8

What is the difference in stable and variant angina?

Answer 8

Stable- occulusion

Variant- spasm

Question 9

What occurs in all forms of angina?

Answer 9

Decreased myocardial O2

Question 10

How can you reduce myocardial O2 demand?

Answer 10

By drugs acting directly on the heart

E.g. B1-adrenoceptor blockers

Question 11

What are B1-adrenoceptor blockers?

Answer 11

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

Question 12

What do B1-adrenoceptors do?

Answer 12

Decreases heart rate and force→ decreases myocardial work

Decrease myocardial O2 demand

Question 13

What types of angina are B1-adrenoceptors used?

Answer 13

All form

Question 14

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

Answer 14

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

Question 15

What does Ivabradine do?

Answer 15

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

Question 16

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

Answer 16

Dilatation of arteries
Dilatation of veins
Venous dilatation

Question 17

How do vasodilator drugs dilate arteries?

Answer 17

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

Question 18

How do vasodilator drugs dilate veins?

Answer 18

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

Question 19

How do vasodilator drugs cause venous dilatation?

Answer 19

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

Question 20

What is the Starling mechanism?

Answer 20

More blood, more contraction

Stretch heart further stronger contraction

Question 21

What is the Bainbridge (atrial) reflex?

Answer 21

A sympathetic reflex initiated by increased blood in the atria

Question 22

What does the bainbridge reflex cause stimulation of?

Answer 22

SA node

Stimulates baroreceptors in the atria causing increases SNS stimulation

Question 23

What are nitrovasodilators?

Answer 23

Most commonly used anti-anginals

E.g. GTN, amyl nitrite, isosobide dinitrate, isosobide mononitrate

Question 24

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

Answer 24

Taken as sub-lingual tablet or spray

Not orally active (destroyed by first-pass metabolism)

Question 25

How is Amyl nitrate (volatile liquid) taken?

Answer 25

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

Question 26

What are the uses of nitrovasodilators?

Answer 26

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

Question 27

How are isosobide dinitrate and isosobide mononitrate taken?

Answer 27

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

Question 28

What are all nitrovasodilators?

Answer 28

Pro drugs

Question 29

What are nitrovasodilators?

Answer 29

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

Question 30

What are nitrovasodilators termed?

Answer 30

"NO donors"

Question 31

What do nitrovasodilators mimic?

Answer 31

Action of endothelium- derived NO

Question 32

What does nitric oxide activate?

Answer 32

Soluble guanylate cyclase (sGC) | Cytoplasmic (soluble) enzyme

Question 33

What does the receptor on soluble guanylate cyclase contain?

Answer 33

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

Question 34

What does NO bind to?

Answer 34

Haem receptors

Question 35

What does the binding of NO to haem receptors cause?

Answer 35

Enzyme activation Converts GTP to cGMP Increased cGMP causes vasodilation

Question 36

What are anti anginal actions of nitrovasodilators?

Answer 36

Venous dilatation > arterial dilatation

Question 37

What are the side effects of nitrovasodilators?

Answer 37

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

Question 38

When do L-type voltage operated calcium channels open?

Answer 38

Upon membrane depolarisation

Question 39

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

Answer 39

Cardiac and vascular smooth muscle

Question 40

What is the mechanism of L-type channel block?

Answer 40

Open channel block Allosteric modulation Tissue selectivity

Question 41

What drugs use the open channel block mechanism?

Answer 41

Verapamil and diltiazem work this way

Question 42

What is allosteric modulation?

Answer 42

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

Question 43

What is tissue selectivity?

Answer 43

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

Question 44

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

Answer 44

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

Question 45

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

Answer 45

Decreases after-load | Decreases myocardial O2 demand

Question 46

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

Answer 46

Decreases myocardial O2 demand

Question 47

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

Answer 47

All forms

Question 48

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

Answer 48

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

Question 49

What is vasospasm?

Answer 49

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

Question 50

What is a coronary steel?

Answer 50

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

Question 51

What does Nifedipine cause?

Answer 51

Coronary steal in 10% of patients

Question 52

What are other uses of L-type blockers?

Answer 52

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

Question 53

What are adverse actions of L-type blockers?

Answer 53

Coronary steal Headache Constipation

Question 54

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

Answer 54

Heart block | Cardiac failure

Question 55

What are the steps following the diagnosis of stable angina?

Answer 55

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