Pharmacological treatment of angina

Question 1

What is the window for coronary flow in the heart

Answer 1

Where the aortic pressure is greater than ventricular pressure (coronary arteries are compressed in systole)

Question 2

What shrinks the window for coronary blood flow?

Answer 2

• Shortening diastole
– e.g. increased heart rate

• Increased ventricular end diastolic pressure
– e.g. aortic valve stenosis

• Reduced diastolic arterial pressure
– e.g. mitral or aortic valve incompetence, heart failure

Question 3

Discuss coronary ischaemia and infarction

Answer 3

• Coronary ischaemia usually the result of atherosclerosis
– Causes angina
• Sudden ischaemia is usually caused by thrombosis
– May result in cardiac infarction
• Coronary spasms sometimes causes angina
– “variant” angina
• Cellular calcium overload results from ischaemia
– may cause cell death and dysrhythmias

Question 4

Discuss angina pectoris

Answer 4

• Chest pain due to inadequate supply of oxygen to the heart
– Typically severe and crushing
– “Tight, constricting, dull or heavy”
–SIGN Guidelines

• Characteristic distribution of pain
– Often retrosternal, or left side of chest and can radiate to left arm, neck, jaw and back
– Brought on by exertion, cold or excitement
– Thought chemical factors that cause pain in skeletal muscle (i.eK+,H+ and adenosine) are responsible

• Angina can accompany or be a precursor of a heart attack

Question 5

What are the three classes of angina and what type of ischaemia are they associated with

Answer 5

Printzmetal’s variant angina (vasospasm)
- Supply ischaemia

Chronic stable angina (fixed stenosis)
-Demand ischaemia

Unstable angina (thrombus)
-Supply ischaemia

Question 6

Discus the angina classes

Answer 6

• Stable Angina
– Predictable chest pain on exertion
– Caused by a fixed narrowing of the coronary arteries

• Unstable Angina
– 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)

• Variant (Prinzmetal) Angina
– Uncommon
– Caused by coronary artery spasm
– Not completely understood, but sometimes associated with atherosclerosis

Question 7

What are some treatments to reduce chest pain symptoms?

Answer 7

– Beta-blockers
– Nitrates
– Calcium channel antagonists
– Nirocandil (K+ channel activator)
– Ivabradine (HCN Channel blocker)
– Ranolazine (fatty acid oxygenation inhibitor(?))

(Don’t need to know brackets)

Question 8

What are some treatments to prolong survival in those with angina

Answer 8

– Beta-blockers
– Aspirin
– Statins
– (Angiotensin Converting Enzyme Inhibitors)
– (AngiotensinII Receptor Blockers) - (ACEI or ARBs)

Question 9

How do you treat symptoms of angina

Answer 9

• Offer short-acting nitrate for preventing/treating episodes of angina.

• Offer first-line treatment:
– Usually a β-blocker, but a calcium channel blocker (CCB)
can be considered.

• If control by β-blockers not optimal, addition of CCB can be considered.
• If beta blocker or CCB monotherapy ineffective and the other option is contraindicated, there are a few other drugs may be additionally used (e.g. nicorandil or ivabradine).

Question 10

What is a short acting nitrate

Answer 10

Glyceryl trinitrate (GTN) tablets/spray

Question 11

How do antianginal drugs work?

Answer 11

• Mainly work by ↓ the metabolic demand of the muscle

• Organic nitrates, nicorandil and calcium antagonists are vasodilators
– ↓ preload or afterload

• b-blockers and ivabradine slow down the heart
– ↓ the metabolic demand of the muscle

Question 12

Discuss organic nitrates

Answer 12

• Glyceryl trinitrate and isosorbide mononitrate
– Powerful vasodilators

– Work by being metabolised to nitric oxide (NO) and relax smooth muscle (particular vascular smooth muscle)

– Act on veins to ↓ cardiac preload
• Higher concentrations can affect arteries, therefore ↓afterload

– ↓ cardiac workload is helped by dilaIon of collateral coronary vessels
• therefore improves distribution of coronary blood flow towards ischaemic areas
• Dilation of constricted coronary vessels is particularly beneficial in variant angina
(basically increases flow in arteries that bypass og)

Question 13

Discuss clinical uses of organic nitrates in angina

Answer 13

• Stable Angina
– Prevention by sublingual glyceryl trinitrate shortly before
exertion or isosorbide mononitrate long before

• Unstable angina
– intravenous glyceryl trinitrate (GTN)

• Unwanted effects are common, headache and postural hypotension may occur

Question 14

What are some other uses of organic nitrates (not angina)

Answer 14

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

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

Question 15

Discuss b(beta)-blockers

Answer 15

• Important (first line treatment) in the prophylaxis and treatment of stable and unstable angina
• ↓cardiac oxygen consumption by slowing the heart
• Also have an antidysrhythmic action – reduce death after MI
• Bisoprolol, Atenolol

Question 16

Discuss calcium channel blockers (CCBs)

Answer 16

• Preventing opening of voltage-gated L-type Ca2+ channels
– Therefore block Ca2+ entry
– Mainly affect the heart and smooth muscle to inhibit calcium entry upon muscle cell depolarisation

• Two main types:
– Dihydropyridine derivatives, e.g. amlodipine and lercanidipine
– Rate-limiting, e.g. verapamil and diltiazem

• Vasodilator effect mainly on resistance vessels
– Therefore reduces afterload
– also dilate coronary vessels (important in variant angina)

• Verapamil and diltiazem can reduce and impair AV conduction and myocardial contractility

Question 17

What are the clinical uses of calcium channel blockers (CCBs) in angina

Answer 17

• Choice depends on comorbidity and drug interactions
– 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
– Diltiazem or verapamil used but contraindicated in heart failure, bradycardia, AV block or in presence of Beta-Blocker

• Side effects include:
– headache, constipation, ankle oedema

Question 18

What are some other (not angina) uses of CCBs?

Answer 18

• 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 lercanidipine

Question 19

Discuss potassium channel activators

Answer 19

• Nicorandil
– combines activation of potassium K+ATP channels
with nitrovasodilator actions
• Causes hyperpolarisation of vascular smooth muscle
– both an arterial and venous dilator
– causes headaches, flushing and dizziness
– used for patients who remain symptomatic despite optimal management with other drugs

Question 20

What are some other anti-anginals that don’t fall into the discussed categories

Answer 20

• Ivabradine
– Inhibits funny “f”-type channels in heart
– Reduces cardiac pacemaker activity
• Therefore inhibits heart rate

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

Question 21

Learning outcomes

Answer 21

Explain the pathology underlying the different categories of angina.
Categorise the drugs used to treat the symptoms of angina and those that prolong survival.
Relate the mechanism of action of drugs to used to treat the symptoms of angina to their therapeutic outcome and side-effects.