Clinical Pharmacology of Stable coronary disease

Question 1

How does angina arise

Answer 1

mismatch between myocardial oxygen supply and myocardial demand

Question 2

What increases myocardial demand

Answer 2

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

Question 3

How is angina treated

Answer 3

1. Relieve symptoms
   * Reduce workload
   * Improve coronary blood flow
2. Slow/halt the disease process
3. Prevent myocardial infarction
4. Prevent premature death

Question 4

What are the different pharmacotherapy for angina

Answer 4

Rate limiting
Vasodilators
Sodium channel activators

Question 5

What are the different rate limiting options

Answer 5

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

Question 6

What are the different vasodilator options

Answer 6

Nitrates – nitric oxide
Calcium channel blocker
Potassium channel activator

Question 7

What are the sodium channel activator options

Answer 7

Ranolazine

Question 8

What are the disease modifying pharmacotherapies

Answer 8

Antiplatelets
Cholesterol lowering

Question 9

What are the different antiplatelet drugs

Answer 9

Aspirin
Clopidogrel
Ticagrelor
Prasugrel

Question 10

What are the different cholesterol lowering drugs

Answer 10

HMG-CoA reductase inhibitors
Fibrates
PCSK-9 inhibitors

Question 11

What is the mechanism of action of beta-adrenoreceptors antagonists

Answer 11

Reversible inhibitor of beta 1 and 2 receptors
Blocks sympathetic system
Selective vs Non-selective

Question 12

What are the benefits of beta blockers

Answer 12

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

Question 13

What are the side effects of beta blockers

Answer 13

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

Question 14

What are the selective and non-selective beta blockers

Answer 14

Cardio selective:
* Bisoprolol
* Metoprolol – shorter acting
* Atenolol

Non-selective:
* Carvedilol
* Propranolol

Question 15

What is the mechanism of action of calcium channel blockers

Answer 15

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 16

What are the benefits of calcium channel blockers

Answer 16

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

Question 17

What are the side effects of calcium channel blockers

Answer 17

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

Question 18

What are the side effects of calcium channel blockers

Answer 18

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

Question 19

What are the dihydropyridine and non-dihydropyridines

Answer 19

Dihydropyridine (DHP)
* Amlodipine
* Felodipine
* Nifedipine

Non-dihydropyridine (N-DHP)
* Verapamil
* Diltiazem

Question 20

What is the mechanism of action of nitrates

Answer 20

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

Question 21

What are the benefits of nitrates

Answer 21

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

Question 22

What are the side effects of nitrates

Answer 22

Severe aortic stenosis
Hypotension
Headache

Question 23

What is the mechanism of action of potassium channel activator

Answer 23

Activates ATP sensitive potassium channels
causing potassium influx

Resultant inhibition of Calcium influx:
1. Negative inotrope
2. Smooth muscle relaxation (coronary and peripheral)

Question 24

What are the side effects of potassium channel activators

Answer 24

Hypotension
GI ulceration

Question 25

What is the mechanism of action of ivabradine

Answer 25

Inhibits channels located in SA node
Only works when patient is in sinus rhythm

Question 26

What are the benefits of ivabradine

Answer 26

Heart rate – when in sinus rhythm
Reduces rates of infarction

Question 27

What are the side effects of ivabradine

Answer 27

Bradycardia
SA node disease

Question 28

What is the mechanism of action of ranolazine

Answer 28

Inhibits late sodium current in myocardial cells
Inhibits rapid phase of delayed potassium rectifier current, (Na+/K+ balance across membrane)
Reduces intracellular calcium
Metabolic action via alpha 1 and beta 1 mediation of fatty acid oxidation

Question 29

What are the benefits of ranolazine

Answer 29

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

Question 30

What are the side effects of ranolazine

Answer 30

Avoid use with CYP enzyme inhibitors
Prolongs QTc

Question 31

What is the function of HMG-CoA reductase inhibitors

Answer 31

Reduces cholesterol production:
Atorvastatin
Simvastatin
Rosuvastatin

Question 32

How is cholesterol absorbtion reduced

Answer 32

Ezetimibe – inhibits cholesterol uptake in gut
Liver forced to increase uptake from blood stream therefore lowing LDL levels
Often used in conjunction with statin

Question 33

What are the benefits of lipid lowering therapy

Answer 33

Reduced rate of MI
Plaque stabilisation
Reduce LDL and increase HDL

Question 34

What are the LDL targets

Answer 34

Low risk – 3.0
Moderate risk – 2.5
High risk (recent MI) – 1.8