Clinical Pharmacology of the Stable Coronary Artery Disease

Question 1

What are epicardial arteries?

Answer 1

on surface

Question 2

What is microcirculation?

Answer 2

perforates through all muscle

Question 3

What is stable angina?

Answer 3

A clinical syndrome of predictable chest pain precipitated by exercise or emotional stress, which increase myocardial oxygen demand.

Question 4

Features of stable angina?

Answer 4

Predictable: The symptoms of stable angina usually occur with a predictable pattern, such as during exercise or exertion, and they tend toimprove or go away with rest.

Consistent: The symptoms of stable angina tend to be consistent over time, with similar frequency, intensity, and duration from episode toepisode.

Relieved by medication:Effective in both preventingand resolving acute attacks

Not an emergency: Although stable angina can be uncomfortable,it isnot usually a medical emergency anddoes notrequire immediatemedical attention.

Question 5

What is Atypical angina?

Answer 5

Defined as stable angina but with symptoms not clearly identifiable as ischaemic chest pain.
Breathlessness
Burning/reflux/burping

Question 6

Risk factors?

Answer 6

hypertension
smoking
diabetes
hyperlipidaemia

(modifiable)

family history
post menopausal females
other arterial disease
male

(non modifiable)

Question 7

Why does angina arise?

Answer 7

Angina arises because of a mismatch between myocardial oxygen supply and the myocardial demand.

Question 8

Cure for angina?

Answer 8

So, increase myocardial blood flow and reduce the demand

Question 9

What increases myocardial demand?

Answer 9

Heart rate
Preload
Afterload
Myocardial contractility – systolic function
Myocardial relaxation – diastolic function
Myocardial wall stress

Question 10

How do we treat?

Answer 10

Relieve symptoms
Reduce workload- beta blockers
Improve coronary blood flow

Slow/halt the disease process

Prevent myocardial infarction

Prevent premature death

Question 11

Pharmacotherapy for symptoms ?

Answer 11

Rate Limiting
Beta-adrenoreceptor antagonist
Calcium channel blocker (L-type)
Ivabradine (f-channel)

Vasodilators
Nitrates – nitric oxide
Calcium channel blocker
Potassium channel activator

Sodium channel activators
Ranolazine

Question 12

Pharmocotherapy for disease modifying?

Answer 12

Antiplatelets-
Aspirin
Clopidogrel
Ticagrelor
Prasugrel

Cholesterol lowering-
HMG-CoA reductase inhibitors
Fibrates
PCSK-9 inhibitors

Question 13

Mechanism of action of Beta Blockers (Beta-adrenoreceptor antagonist)
?

Answer 13

Reversible inhibitor of the beta1 and beta2 receptors
Block the sympathetic system
Selective vs Non-selective

Question 14

Cardio selective beta blockers?

Answer 14

Bisoprolol
Metoprolol – shorter acting
Atenolol (cardio selective-ish)

Question 15

Non selective beta blockers?

Answer 15

Carvedilol
Propranolol

Question 16

Side effects of beta blockers?

Answer 16

Asthma
Peripheral vascular disease
Raynaud’s syndrome
Acute heart failure
Bradycardia or heart block
Fatigue
Impotence

Question 17

Benefits of beta blockers?

Answer 17

Decrease major determinants of myocardial oxygen demand
Heart rate – reduce myocardial workload
Contractility
Systolic wall tension – improve relaxation
Increases diastolic perfusion time
Reduces rate of ischaemic events and mortality

Question 18

What are the rate limiting calcium channel blockers?

Answer 18

non dihydropyridine
Verapamil
Diltiazem

Question 19

What are the reducing systemic vascular resistance calcium channel blockers?

Answer 19

dihydropyridine
Amlodipine
Felodipine
Nifedipine

Question 20

Mechanism of calcium channel blockers?

Answer 20

Prevent calcium influx into myocytes and smooth muscle arteries/arterioles by blocking L-type Ca channel
Dihydropyridine mostly relax smooth muscle
Non-dihydropyridines mostly reduce heart rate

Question 21

Benefits of calcium channel blockers?

Answer 21

Heart rate - Exclusively NDHP like Verapamil/Diltiazem
Reduce contractility (NDHP)
Reduce afterload (DHP)
Increases diastolic perfusion time (NDHP)

Question 22

Side effects/ cautions of calcium channel blockers?

Answer 22

Peripheral oedema (DHP)
Bradycardia/heart block (NDHP)
Hypotension (Both)
Reduced LV function
Headache
Flushing

Question 23

What do nitrates (vasodilators ) do?

Answer 23

nitrates release nitric oxide which potentiates smooth muscle relaxation

Question 24

Mechanism of action of vasodilators?

Answer 24

Nitric Oxide mediated smooth muscle relaxation
Non-selective
Long-acting preparations most effective
Sublingual has utility for acute attacks

Question 25

Side effects of vasodilators?

Answer 25

Severe aortic stenosis Hypotension Headache

Question 26

Benefits of vasodilators?

Answer 26

Reduce preload and afterload – Therefore myocardial workload Improve coronary flow via vasodilation (Epicardial arteries and improve blood supply) Doesn't reduce mortality

Question 27

Mechanism of action of vasodilator (Nicorandil)- potassium channel activator?

Answer 27

Activates ATP sensitive potassium channels causing potassium influx Resultant inhibition of Calcium influx Negative inotrope Smooth muscle relaxation (coronary and peripher

Question 28

Side effects of nicorandil?

Answer 28

Hypotension GI ulceration

Question 29

Mechanism of action of second line - rate limiting "Ivabradine"?

Answer 29

Inhibits the 'funny' channels located in SA node. Only works when patient is in sinus rhythm

Question 30

Side effects of ivabradine?

Answer 30

Bradycardia SA node disease

Question 31

Benefits of Ivabradine?

Answer 31

Heart rate – when in sinus rhythm Reduces rates of infarction

Question 32

Mechanism of action of Ranolazine?

Answer 32

Inhibits late sodium current in myocardial cells  Inhibits rapid phase of delayed potassium rectifier current. Therefore, Na+/K+ balance across membrane).  This also reduces intracellular calcium. Theorised metabolic action via alpha 1 and beta 1 mediation of fatty acid oxidation

Question 33

Side effects/ cautions of Ranolazine?

Answer 33

Avoid use with CYP enzyme inhibitors Prolongs QTc

Question 34

Benefits of Ranolazine?

Answer 34

Reduced O2 demand due to reduced wall stress (easier to perfuse microcirculation) ? Beneficial antiarrhythmic effects via Na+/K+ channels (uncertain utility).  

Question 35

Slow disease progression- lipid lowering therapy?

Answer 35

HMG-CoA Reductase inhibitors Reduces cholesterol production Atorvastatin Simvastatin Rosuvastatin Reduce cholesterol absorption Ezetimibe – inhibits cholesterol uptake in the gut Liver forced to increase uptake from blood stream therefore lowing LDL levels Often used in conjunction with a statin Fibrates  Bezafibrate Fenofibrate Benefit Reduced rate of MI Plaque stabilisation Reduce LDL and increase HDL LDL Targets Low risk – 3.0 Moderate risk – 2.5 High risk (recent MI) – 1.8

Question 36

Antiplatelets?

Answer 36

Thromboxane A2 inhibitor Aspirin Inhibits platelet activation via TXA2 pathway P2Y12 inhibitors Clopidogrel Ticagrelor Prasugrel Inhibits platelet activation via ADP mediated pathway