Treatment of Angina

Question 1

Define angina pectoris.

Answer 1

Chest pain due to inadequate supply of oxygen to the heart.
– Typically severe and crushing
– Feeling of pressure and suffocation behind the breastbone

Question 2

Identify classes of drugs/drugs used to reduce chest pain symptoms.

Answer 2

– Beta-blockers
– Nitrates
– Calcium channel antagonists
– Nirocandil (Potassium Channel Activator) 
– Ivabradine (If channel inhibitor)
– Ranolazine

Question 3

Identify classes of drugs/drugs used to prolong survival.

Answer 3

– Beta-blockers
– Aspirin
– Statins
– (Angiotensin Converting Enzyme Inhibitors) 
– (Angiotensin II Receptor Blockers)

Question 4

Relate the coronary window to angina.

Answer 4

Closing window for coronary flow will increase the risk of angina.

Question 5

Identify factors which may cause a closing of the window for coronary flow (explain what physiological or pathological change could give rise to each factor).

Answer 5

1. Shortening diastole (e.g. increased HR)
2. Increased ventricular end diastolic pressure (e.g. aortic valve stenosis)
3. Reduced diastolic arterial pressure (e.g. mitral or aortic valve incompetence, heart failure)

Question 6

Will increasing HR lead to angina in normal healthy people ?

Answer 6

No

Question 7

Identify possible causes of angina, explaining the causes of each.

Answer 7

• Coronary ischaemia (usually due to atherosclerosis and will lead to angina. If sudden ischaemia, probably due to thrombus and leads to cardiac infarction which in turn will lead to angina)
• Coronary spasms (spontaneous, causes variant angina)

Question 8

Define cardiac infarction.

Answer 8

“Death of the cells of an area of the heart muscle (myocardium) as a result of oxygen deprivation, which in turn is caused by obstruction of the blood supply”

Question 9

Name other clinical issues related to cardiac ischemia, other than angina.

Answer 9

Cellular Calcium Overload, may cause cell death and dysrhythmias.

Question 10

Describe the distribution of pain in angina.

Answer 10

Chest, arm, neck, jaw

Question 11

List any exacerbating factors for angina.

Answer 11

Exertion, cold or excitement

Question 12

What is the pain aspect of angina due to ?

Answer 12

Thought chemical factors that cause pain in skeletal muscle (i.e K+, H+ and adenosine) are responsible

Question 13

How is angina related to heart attacks ?

Answer 13

Angina can accompany or be a precursor of a heart attack

Question 14

Categorize the different types of angina. What is this classification based on ?

Answer 14

Printzmetal’s variant angina (vasospasm)- Supply Ischemia (reduced oxygen supply)

Chronic stable ischemia (fixed stenosis i.e. atherosclerotic plaque causing reduced blood flow)- 
Demand Ischemia (oxygen demand increases)

Unstable angina (thrombus)- 
Supply Ischemia (reduced oxygen supply)

Partly based on what’s causing it.

Question 15

Does the occlusion response for unstable angina (thrombus) have to be complete ?

Answer 15

No, can be either complete or incomplete

Question 16

Describe stable angina.

Answer 16

– Predictable chest pain on exertion (because it’s a O2 demand problem) but NOT presenting immediate risk (hence, will mainly treat using drugs to relieve chest pain)
– Caused by a fixed narrowing of the coronary arteries
– Treated by ↓ workload of the heart and ↓oxygen requirement
– Also use drugs to prolong survival (e.g. aspirin, statins, ACE inhibitors)

Question 17

Describe unstable angina.

Answer 17

–Occurs at rest and with less exertion than stable angina
–Associated with a thrombus around a ruptured atheromatous plaque but without complete occlusion of the vessel (similar to MI)

Question 18

Describe Variant (Prinzmetal) Angina.

Answer 18

– Uncommon
– Caused by coronary artery spasm
– Not completely understood, but sometimes associated with atherosclerosis

Question 19

How do antiaginal drugs work, in general ?

Answer 19

Mainly work by ↓ the metabolic demand of the muscle (By decreasing the preload or after-load, or by addressing metabolic demands of the muscle itself)

Question 20

Give examples of antiaginal drugs, explaining how they reduce angina.

Answer 20

Organic nitrates, nicorandil and calcium antagonists are vasodilators
–↓preload or a fterload

b-blockers and ivabradine slow down the heart
– ↓ the metabolic demand of the muscle (increase window for coronary flow)

Question 21

Which types of angina are beta blockers used for ?

Answer 21

Important (first line treatment) in the prophylaxis and treatment of stable and unstable angina.

Question 22

How do beta blockers work in reducing angina ? Give examples of beta blockers.

Answer 22

• Decrease Oxygen consumption by slowing down the heart (block adrenaline or NA binding to beta 1 receptors, hence increase window of coronary flow)
• Also have an anti-dysrhythmic action (reduce risk of death after MI)

Bisoprolol, Atenolol

Question 23

How do Calcium antagonists work in reducing angina ? Give examples of Calcium antagonists.

Answer 23

• Prevent opening of voltage gated L-type Calcium channels (i.e. block Calcium inflow upon muscle depolarisation)
Mainly affect the heart and smooth muscle
-vasodilator effect mainly on resistance vessels (i.e. reduces afterload)
-also dilate coronary vessels (important in variant angina)

• Verapamil and diltiazem can reduce and impair AV conduction and myocardial contractility
• Amlodipine and lercanidipine more involved with vasculature (i.e. arteries etc) than the heart itself

Two types:

• Dihydopyridine derivatives (e.g. amlodipine and lercanidipine)
• Rate-limiting (e.g. verapamil and diltiazem)

Question 24

Describe the clinical uses of Calcium antagonists in angina (which calcium antagonists to use for certain situations ? which not to use for certain situations ?)

Answer 24

• Choice depends on comorbidity and drug interactions:

1) Amlodipine or lercanidipine:
- safe in patients with heart failure
- used instead of a Beta-Blocker in Prinzmetal angina or alongside beta-blockers in most angina

2) Diltiazem or verapamil:
- used but contraindicated in heart failure, bradycardia, AV block or in presence of beta-blocker

Question 25

Identify side effects of calcium antagonists.

Answer 25

headache, constipation, ankle oedema

Question 26

Identify other clinical uses of calcium antagonists .

Answer 26

• Antidysrhythmics (mainly verapamil)

• Slows ventricular rate in rapid atrial fibrillation
• Prevents recurrence of supraventricular tachycardia (SVT)
• No effect on ventricular arrhythmias

• Hypertension
– Mainly amlodipine or lercanidpine

Question 27

How do Organic Nitrates work in reducing angina ? Give examples of Calcium antagonists.

Answer 27

• Powerful vasodilators

• Work by being metabolised to NO and relax smooth muscle (particularly vascular smooth muscle)
• Therefore, act on veins to reduce cardiac preload
• At higher concentrations, dilates arteries (decreases afterload)
• Dilation of collateral coronary vessels helps reduce cardiac workload, which improves distribution of coronary blood flow toward ischemic area (Dilation of constricted coronary vessels is particularly beneficial in variant angina)

EXAMPLES: Glyceryl trinitrate (GTN) and isosorbide mononitrate

Question 28

How are organic nitrates administered ?

Answer 28

Normally sublingually/through spray

To achieve arterial dilation, need high concentration given intravenously

Question 29

Identify Clinical Uses of Organic Nitrates in Angina.

Answer 29

• Stable angina
– Prevention by sublingual glyceryl trinitrate (GTN) shortly before exertion or isosorbide mononitrate long before

• Unstable angina
– intravenous GTN

Question 30

Are there any side effects to organic nitrates ?

Answer 30

Yes, unwanted effects are common, headache and postural hypotension may occur

Question 31

List any other clinical uses of organic nitrates (besides angina).

Answer 31

• Acute heart failure (in specific circumstances)
– intravenous GTN

• Chronic Heart Failure (CHF)
– isosorbide mononitrate with hydralazine in patients of African American origin especially (or patient who cannot tolerate more commonly used CHF drugs)

Question 32

What kind of drug is Nicorandil ?

Answer 32

Potassium Channel Activator

Question 33

How does Nicorandil work in reducing angina ?

Answer 33

• combines activation of potassium K+ATP channels (causes hyperpolarisation of vascular smooth muscle, lower force generated) with nitrovasodilator actions (donator of NO)
- both an arterial and venous dilator (hence, mainly decreases pre-load but may also decrease afterload)

Question 34

Identify Clinical Uses of Nicorandil in Angina.

Answer 34

Used for patients who remain symptomatic despite optimal management with other drugs

Question 35

Identify any side effects of Nicorandil.

Answer 35

Headaches, flushing and dizziness

Question 36

Identify other antianginals besides Nicorandil, organic nitrates, Calcium antagonists and beta blocker. Explain how each of these works.

Answer 36

• Ivabradine
– Inhibits funny “f”-type channels in SAN
– Reduces cardiac pacemaker activity (i.e. inhibits heart rate, but does not affect contractility of the heart so no risks associated with that)

• Ranolazine
– Unique anti-anginal used as a last resort

Question 37

Explain the pharmacological management involved in angina.

Answer 37

FIRST LINE THERAPY

• Beta blockers (to relieve symptoms of stable angina)
• Patients intolerant to that can be treated using rate-limiting calcium antagonists, long-acting nitrates, or nicorandil

NITRATES
-Sublingual GNT tablets (short-acting) or spray should be used for the immediate relief of angina and before performing activities that are known to bring on angina (in addition to first line therapy)

COMBINATION THERAPY

• When adequate control of anginal symptoms is not achieved with beta-blockers, a calcium antagonist should be added (rate-limiting calcium antagonists should be used with caution when used with beta blockers)
• Patients whose symptoms are not controlled on max therapeutic doses of two drugs should be considered for referral to a cardiologist

DRUG INTERVENTIONS TO PREVENT NEW VASCULAR EVENTS

• All patients with stable angina due to atherosclerotic disease should receive long term standard aspiring and statin therapy
• All patients with stable angina should be considered for treatment with angiotensin-converting enzyme inhibitors (ACE inhibitors).