Management of Stable Angina with Drugs

Question 1

When is the myocardium perfused with oxygenated blood

Answer 1

During diastole (as the coronary vessels are squished during systole)

Question 2

What is myocardial oxygen demand a function of

Answer 2

How hard the heart is having to work (heart rate increases) and ventricular wall tension (determined by the pressure, chamber volume and wall thickness)

Question 3

Describe the vasculature of the heart

Answer 3

Aorta, anterior surface: left coronary artery (LCA) initially branches to yield the left anterior descending (LAD) or anterior interventricular artery, the LCA then progresses to become he left marginal artery (LMA) and left circumflex artery (Cx- left posterior surface). Right coronary artery (RCA) comes from the aorta and branches to form the right marginal artery (RMA) anf the posterior interventricular artery (Plc) posteriorly (right posterior surface)

Question 4

What is coronary blood flow determined by

Answer 4

Myocardial oxygen demand

Question 5

What is resting coronary blood flow

Answer 5

c.224 ml/min

Question 6

What can vigorous exercise flow be

Answer 6

c.800+ ml/min

Question 7

Why is there a factor 4 increase in coronary blood flow during vigorous exercise

Answer 7

The heart requires a lot of oxygen

Question 8

What does compromised coronary artery flow have major implications for

Answer 8

The myocardium

Question 9

What are risk factors for coronary artery disease

Answer 9

Obesity, hypercholesterolaemia, family history of CAD, hypertension, smoking, diabetes, kidney disease (>men, >65 women), physical inactivity and psychosocial stress

Question 10

What does the fact that many of the risk factors for coronary artery are lifestyle related mean

Answer 10

There is need for primary intervention and empowering patients to take care of their own health

Question 11

What does normal blood flow rely on

Answer 11

Vessels elastically expanding after pulsatile ejections

Question 12

What can make artery walls less elastic and more rigid and what impact does this have

Answer 12

Age and risk factors make artery walls less elastic and more rigid, increasing cardiac inotropy to compensate

Question 13

What can increasing cardiac inotropy lead to

Answer 13

Ventricle hypertrophy and increased myocardial oxygen demand

Question 14

What does the fact that you have a pulse wave mean

Answer 14

That vessels dilate after each heart beat which males the job of the heart less hard which reduces afterload

Question 15

What happens if the vessels are stiffer and more rigid

Answer 15

They can’t accommodate meaning that the heart has to work harder which increases the amount of muscle resulting in left ventricular hypertrophy which is pathological

Question 16

What are the main features of atherosclerosis

Answer 16

The growth of LDL-cholesterol laden plaques in the sub-endothelium

Question 17

Describe the process of atherosclerosis and what it leads to

Answer 17

The process is multi-factorial and leads to tissue ischaemia

Question 18

What effects do the plauques have on the vessel

Answer 18

The plaques narrow the bore of the vessel resulting in a lack of oxygenated blood that can pass as the vessels are partially occluded

Question 19

When is ischaemia inevitable

Answer 19

If oxygenated blood cannot meet the myocardial demand

Question 20

What happens in myocardial anaerobic glycolysis

Answer 20

Large quantities of lactate are generated from pyruvate

Question 21

When does myocardial ischaemia occur

Answer 21

When the vessel bore id reduced

Question 22

Why is it formed and what does lactate trigger

Answer 22

Lactate is produced during ischaemia as there is a lack of oxygenated blood and this can trigger pain

Question 23

What are the signs and symptoms of angina

Answer 23

Crushing, burning or ‘tight’ chest pain often accompanied by shortness of breath, nausea and sweating

Question 24

What determines the nature/ severity of angina symptoms

Answer 24

Which coronary arteries and how narrowed they are

Question 25

What are angina symptoms precipitated by

Answer 25

Physical exertion or emotional stress

Question 26

What are angina symptoms relieved by

Answer 26

By rest (relieved within minutes)

Question 27

What are examples of physical exertion that can bring on angina pain

Answer 27

Gardening, walking for the bus and lifting shopping

Question 28

When is transient ischaemia resolved

Answer 28

When you stop exertion and rest

Question 29

What do angina symptoms warrant

Answer 29

Further investigation and conformation that it is stable angina

Question 30

When do acute coronary symptoms appear

Answer 30

At rest, although may be due to vasospasm

Question 31

What does ACS usually indicate

Answer 31

Unstable (vulnerable) plaque ruture (whcih coronary arteries and how long determine the nature of the nature of the symptoms and severity) with thrombus fragments adding to the narrowing of the coronary vessels

Question 32

What did acute coronary syndrome used to be called

Answer 32

Unstable angina

Question 33

What does a thrombus do

Answer 33

Further occlude a blood vessel resulting in transient narrowing of a vessel

Question 34

What does the fact that acute coronary syndrome is acute mean

Answer 34

It can lead to a full on MI depending on the nature of plaque rupture

Question 35

What ECG changes are seen during exertion with someone with angina

Answer 35

Characteristic 'ST depression' seen on a 12-lead ECG in a patient taking an exercise stress (treadmill) test. People tend to display a relatively normal ECG at rest with normal P, Q, R, S, T waves at rest. Atfer 7 minutes of walking on a treadmill people with angina display characteristic ST depression. When the treadmill is stopped the ECG returns back to normal. People are also asymptomatic at rest

Question 36

What causes ST depression

Answer 36

Ventricular tissue becoming ischaemic

Question 37

What can coronary angiography be used to diagnose

Answer 37

Angina

Question 38

Describe angiography

Answer 38

It is an x-ray based imaging technique that can identify narrowing or partial occlusion of coronary arteries. A radio-opaque contrast dye is injected into the coronaries via a catheter. The catheter goes through the femoral artery and terminates at the start of the coronary vessels. Any narrowing= cardiac ischaemia

Question 39

Describe echocardiography

Answer 39

A non-invasive ultrasound imaging technique that can identify chamber wall motion abnormalities that may indicate coronary artery disease. Can identify problems in walls or valves. Ischaemic conditions give rise to wall motion abnormalities

Question 40

What are drugs being used for symptomatic relief of angina used for

Answer 40

Can be used to reduce/ relieve angina symptoms associated with an episode of ischaemic stress which is symptomatic relief

Question 41

What are prophylactic angina drugs used for

Answer 41

To reduce incidence of angina episodes which is preventative

Question 42

What drug provides symptomatic relief of angina

Answer 42

Glyceryl trinitrate

Question 43

What forms does glyceryl trinitrate come in

Answer 43

IV, sub-lingual spray (goes under the tongue because there are lots of blood vessels which means it quickly dilates coronary vessels) and patch

Question 44

What drug provides preventative relief of angina

Answer 44

Bisoprolol

Question 45

What form does Bisoprolol come in

Answer 45

Tablets

Question 46

What are organic nitrate drugs like isiosorbide mononitrate and glyceryl trinitrate reduced to in the body

Answer 46

Nitric oxide (NO)

Question 47

What is NO

Answer 47

A potent vasodilator

Question 48

Describe the MOA of NO

Answer 48

1. NO activated guanylyl cyclase (GC) in vascualr smooth muscle cells. 2. cGMP increases which activates protein kinase G (PKG). 3. PKG activity prevents Ca2+ entry into smooth muscle cells. 4. Coronary vessels dilate (reducing angina symptoms)

Question 49

What does the fact that calcium can't enter the muscle mean

Answer 49

The muscle can't contract as forcefully

Question 50

What is nitrate tachpylaxis

Answer 50

The body gets used to NO which means that it doesn't work because you become desensitised to NO

Question 51

What are common ADRs of NO

Answer 51

Postural hypotension, tachycardia, throbbing headache

Question 52

What are uncommon ADRs of NO

Answer 52

Flushing, heartburn, nausea, rash, syncope, temporary hypoxaemia, vomiting

Question 53

What are very rare ADRs of NO

Answer 53

Angle-closure glaucoma

Question 54

What are contraindications of NO

Answer 54

Aortic stensosis, cardiac tamponade, constrictive pericarditis, hypertrophic cardiomyopathy, hypotensive conditions, hypovolaemia, marked anaemia, mitral stenosis, raises intracranial pressure due to cerebral haemorrhage, raised intracranial pressure due to head trauma, toxic pulmonary oedema

Question 55

What is the MOA of β1-adrenoreceptor antagonists

Answer 55

Effective means of reducing onset of angina episodes/ attacks. β1-adrenoreceptor antagonists competitively inhibit β1-adrenoreceptors in cardiac tissue, preventing binding of agonists noradrenaline and adrenaline. This has a negative chronotropic an negative ionotropic effect that reduces cardiac output

Question 56

What are ADRS of β1-adrenoreceptor antagonists

Answer 56

Dry eyes, rashes

Question 57

What are contraindications of β1-adrenoreceptor antagonists

Answer 57

Asthma; cardiogenic shock; hypotension; marked bradycardia; metabolic acidosis; phaeochromocytoma (apart from specific use with alpha-blockers); Prinzmetal’s angina; second-degree AV block; severe peripheral arterial disease; sick sinus syndrome; third-degree AV block; uncontrolled heart failure

Question 58

What is the method of action of calcium channel blockers

Answer 58

Impede Ca2+ traffic through L-type voltage-gated channels. The CCB crosses the membrane, binds to the channel and induces a conformational change which forces the channel to remain inactive stopping Ca2+ traffic. Electrical conduction through the heart is dependent on calcium cations. CCB block intracellular Ca2+ channels meaning that Ca2+ is inactive resulting in the tissue being kept in the refractory period and Ca2+ can't get into the contractile myocytes

Question 59

If CCB don't fix the problem what do they do

Answer 59

They stop the problem from happening/ keep a patient stable/ CCB therapeutically keep a patient stable meaning that they stay healthier for longer

Question 60

What is an example of a CCB

Answer 60

Verapamil

Question 61

What do CCB do

Answer 61

Cause vasodilation by preventing smooth muscle cell contraction plus they reduce the force of ventricle contraction and rate-limit the heart reducing cardiac output

Question 62

ADRs of CCB

Answer 62

Common- constipation. Uncommon-ankle oedema, dizziness, fatigue, flushing, headache, nausea, vomiting. Rare- Allergic reactions; angioedema; arthralgia; asystole; bradycardia; erythema; erythromelalgia;gingival hyperplasia after long-term treatment; gynaecomastia after long-term treatment ;heart block; heart failure; hypotension; increased prolactin concentration; myalgia; paraesthesia; pruritus; Stevens-Johnson syndrome; urticaria

Question 63

Contraindications of CCB

Answer 63

Acute porphyrias; atrial flutter or fibrillation associated with accessory conducting pathways (e.g. Wolff-Parkinson-White-syndrome); bradycardia; cardiogenic shock; history of heart failure (even if controlled by therapy); history of significantly impaired left ventricular function (even if controlled by therapy); hypotension; second- and third-degree AV block; sick sinus syndrome; sino-atrial block

Question 64

Describe the MOA of nicorandil

Answer 64

It is a vasodilator. 1. stimulates guanylyl cyclase to increase cGMP this reduce Ca2+ entry into vascualr smooth muscle cells. 2 Activates K+ATP channel effluxer, hyperopolarising cells thus preventing coltage-gated Ca2+ channel activity (cell us hyperpolarised and therefore can't depolarise and switch on voltage-gated Ca2+ channels)

Question 65

What are ADRs of nicorandil

Answer 65

Common or very common- Cutaneous vasodilation with flushing; dizziness; headache (especially on initiation, usually transitory); increase in heart rate (at high doses); nausea; rectal bleeding; vomiting; weakness. Uncommon- angioedema; hypotension; myalgia; oral ulceration. Rare- Abdominal pain; anal ulceration; cholestasis; gastrointestinal ulceration; hepatitis; jaundice;pruritus; rash; skin ulceration. Very rare- eye ulceration.

Question 66

What are contraindications of nicorandil

Answer 66

Acute pulmonary oedema; cardiogenic shock; hypovolaemia; left ventricular failure with low filling pressures; severe hypotension

Question 67

What is the MOA of ivabradine

Answer 67

Rate limiter. : Dose-dependently inhibits the mixed Na+/K+ inward ion current that constitutes the ‘funny current’ in the SA node, reducing pacemaker automaticity. The ‘funny current’ is phase 4 so a rate limiter decreases the frequency of impulse firing in the SA node and therefore decreases pacemaker activity

Question 68

ADRs of ivabradine

Answer 68

Common or very common- Atrial fibrillation; blurred vision; bradycardia; dizziness; first-degree heart block; headache; phosphenes; ventricular extrasystoles; visual disturbances. Uncommon- angioedema; constipation; diarrhoea; dyspnoea; eosinophilia; hyperuricaemia; muscle cramps; raised plasma-creatinine concentration; rash; supreventricular extrasystoles; vertigo. Very rare- second and third-degree heart block; sick sinus syndrome.

Question 69

Contraindications of ivabradine

Answer 69

Acute myocardial infarction; cardiogenic shock; congenital QT syndrome; do not initiate for angina if heart rate below 70 beats per minute; do not initiate for chronic heart failure if heart rate below 75 beats per minute; immediately after cerebrovascular accident; patients dependent on pacemaker; second- and third-degree heart block; severe hypotension; sick-sinus syndrome; sino-atrial block; unstable angina; unstable or acute heart failure

Question 70

What is the MOA of statins

Answer 70

Inhibit hydroxymethyl glutaryl (HMG) CoA reductase (required for cholesterol synthesis), therefore statins limit how much cholesterol we produce.

Question 71

What is one of the best pharmacologicalmeans of reducing CAD risk

Answer 71

Lowering serum LDL cholesterol if >5.2 mmol/L with statins

Question 72

Why are statins not a treatment for angina

Answer 72

Reduce the risk from hypercholesterolaemia. Statins are preventative

Question 73

What are the ADRs of statins

Answer 73

Rare- hepatitis; jaundice. Very rare- hepatic failure; interstitial lung disease; lupus erythematosus-like reactions; pancreatitis

Question 74

What are the contraindications of statins

Answer 74

Elderly; high alcohol intake; history of liver disease; hypothyroidism; patients at increased risk of muscle toxicity, including myopathy or rhabdomyolysis (e.g. those with a personal or family history of muscular disorders, previous history of muscular toxicity and a high alcohol intake)

Question 75

What is the best way to avoid developing coronary artery disease

Answer 75

A healthy lifestyle

Question 76

What type of drugs are nitrates

Answer 76

Symptomatic relief

Question 77

What type of drugs are β1-adrenoreceptor blockers and CCBs

Answer 77

Prophylactic

Question 78

What best describes how Glyceryl trinitrate (GTN) spray relieves angina symptoms

Answer 78

De-nitration of GTN yields nitric oxide (NO) a potent vasodilator in the coronary arteries, relieving ischaemia-induces symptoms

Question 79

What is a voltage-gated calcium channel blocker suitable for treating angina

Answer 79

Nicorandil- both increases cGMP and efflux K+ATP channel activity