Pharmacological Treatment of Angina Flashcards
What is angina pectoris?
- Chest pain due to inadequate supply of oxygen to the heart.
- Typically severe and crushing.
- Feeling of pressure and suffocation behind the breastbone.
Describe the characteristics of pain distribution in angina.
- Chest
- Arm
- Neck
- Jaw
What brings on angina?
- Exertion
- Cold
- Excitement
What is thought to cause the pain associated with angina?
- It is thought that chemical factors that cause pain in skeletal muscle (i.e K+, H+ and adenosine) are responsible.
- Angina can accompany or be a precursor to MI.
List the treatments used to reduce chest pain symptoms associated with angina.
- Beta-blockers
- Nitrates
- Calcium channel antagonists
- Nicorandil
- Ivabradine
- Ranolazine
List the treatments used to prolong survival in patients with angina.
- Beta-blockers
- Aspirin
- Statins
- Angiotensin converting enzyme inhibitors
- Angiotensin II receptor blockers
Describe the coronary blood flow through the left vetricle.
- Left and right coronary arteries feed the blood supply to the heart.
- Most tissues are perfused when the heart contracts.
- Anything that changes the duration of diastole (window for coronary flow) changes the opportunity for perfusion and causes a change in diastolic pressure.
- If the window is short enough, the base diastolic level rises as the level of blood in the ventricle rises.
What factors shrink the window for perfusion?
- Shortening diastole
- Eg. increased heart rate.
- Increased ventricular end diastolic pressure
- Eg. a progressive decline in ventricular emptying; aortic valve stenosis.
- Reduced diastolic arterial pressure
- Eg. mitral or aortic vlve incompetence; heart failure.
Describe the issues with coronary blood flow.
- Myocardium cannot function anaerobically
- Anaerobic glycolysis increases in lactic acid production.
- Arterioles close mechanically during systole.
- Decreased diastolic filling period during exercise.
- Increased oxygen demand and increased metabolic demand during exercise.
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Work output of the heart increases by 6-9x during strenuous exercise
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Uses 70-80% of coronary blood flow oxygen at rest
- Increased demand must be met by increased flow
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Uses 70-80% of coronary blood flow oxygen at rest
Describe the autoregulation of arteriolar radius.
- It matches the demand to blood flow by altering flow at arteriolar level.
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Metabolic control:
- Muscle cell produces byproducts (eg. adenosine) which trigger vascular smooth muscle cells to relax (potentially via an intermediate produced by endothelial cells).
Describe what causes coronary ischaemia.
- Coronary ischaemia is usually the result of atherosclerosis.
- This causes angina.
Describe what causes sudden ischaemia.
- Sudden ischaemia is usually caused by thrombosis.
- This may result in cardiac infarction.
What is variant angina?
- Angina caused by coronary spasms.
- This is the smooth muscle of the heart spontaneously contracting and relaxing.
What is the cellular effect of ischaemia?
- Cellular calcium overload results from ischaemia.
- This may cause cell death and dysrhythmias.
Describe the progression of atherosclerosis.
What are the classes of angina?
- Chronic stable angina
- Fixed stenosis
- Demand ischaemia
- Fixed stenosis
- Unstable angina
- Thrombus
- Supply ischaemia
- Thrombus
- Printzmetal’s variant angina
- Vasospasm
- Supply ischaemia
- Vasospasm
Describe stable angina.
- Predictable chest pain on exertion.
- Caused by a fixed narrowing of the coronary arteries.
- Treated by decreased workload of the heart and therefore decreased oxygen requirement.
- Also use drugs to prolong survival (eg. aspirin, statins, ACE inhibitors).
Describe 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).
Describe variant (Prinzmetal) angina.
- Uncommon
- Caused by coronary artery spasm
- Not completely understood, but sometimes associated with atherosclerosis.
Describe the main mechanism of action of antianginal drugs.
Mainly work by reducing the metabolic demand of the heart.
Which antianginal drugs are vasodilators?
Describe their mechanism of action.
- Organic nitrates
- Nicorandil
- Calcium antagonists
- These are vasodilators!
- They work by reducing preload or afterload of the heart.
Which antianginal drugs slow the heart?
Describe their mechanism of action.
- β-blockers
- Ivabradine
- These slow down the heart.
- They work by decreasing the metabolic demand of the muscle.
Define preload.
Venous pressure and venous return to the heart (end diastolic pressure / volume) (EDP/EDV).
Define afterload.
Aortic / pulmonary artery pressure.
Describe the action of β-blockers in the treatment of angina.
Give examples.
- Important (first line) treatment in the prophylaxis and treatment of stable and unstable angina.
- Decreases cardiac oxygen consumption by slowing the heart.
- Also have an antidysrhythmic action.
- Reduces death after MI.
- Bisoprolol
- Atenolol
Describe the action of calcium antagonists in the treatment of angina.
Give examples.
- Preventing opening of voltage-gated L-type Ca2+ channels
- Therefore block the entry of Ca2+ entry.
- Mainly affect the heart and smooth muscle to inhibit calcium entry upon muscle cell depolarisation.
- Two main types:
- Dihydropyridine derivatives
- Amlodipine
- Lercanidipine
- Rate-limiting
- Verapamil
- Diltiazem
- Dihydropyridine derivatives
- Vasodilator effect mainly on resistance vessels
- Therefore reduces afterload
- Also dilates coronary vessels (important in variant angina)
- Verapamil and diltiazem can reduce and impair AV conduction and myocardial contractility.
Describe the depolarisation of the SA node.
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Phase 1
- Gradual drift upwards in resting membrane potential due to increased gNa+ as ‘funny’ F-type Na+ channels open and decreased gK+ as K+ channels slowly close.
- Transient (T) Ca2+ channels help with the final push.
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Phase 2
- Moderately rapid depolarisation due to Ca2+ entry via slow (L) channels.
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Phase 3
- Rapid repolarisation as elevated internal Ca2+ stimulates opening of K+ channels and an increase in gK+.
What are the clinical uses of calcium antagonists in angina?
- Choice depends on comorbidity and drug interactions.
- Amlodipine or lercanidipine safe in patients with heart failure; used instead of a β-blocker in Prinzmetal angina or alongside β-blockers in most angina.
- Diltiazem or verapamil used but contraindicated in heart failure, bradycardia, AV block or in presence of β-blocker.
- Side effects include:
- Headache
- Constipation
- Ankle oedema
What are the other clinical uses of calcium antagonists?
- Antidysrhythmics
- Mainly verapamil
- Slows ventricular rate in rapid atrial fibrillation.
- Prevents recurrence of supraventricular tachycardia (SVT).
- No effect on ventricular arrhythmias.
- Mainly verapamil
- Hypertension
- Mainly amlodipine or lercanidipine.
Describe the action of organic nitrates in the treatment of angina.
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Glyceryl trinitrate and isosorbide mononitrate
- Powerful vasodilators
- Work by being metabolised to nitric oxide (NO) and relax smooth muscle (particularly vascular smooth muscle).
- Act on veins to decrease cardiac preload.
- Higher concentrations can affect arteries, therefore decrease afterload.
- Decreased cardiac workload is helped by dilation of collateral coronary vessels.
- This therefore improves distribution of coronary blood flow towards ischaemic areas.
- Dilation of constricted coronary vessels is particularly beneficial in variant angina.
Describe the role of the endothelial cells in regulating vascular tone.
What are the clinical uses of organic nitrates in angina?
- Stable angina:
- Prevention by sublingual glyceryl trinitrate shortly before exertion or isosorbide mononitrate long before.
- Unstable angina:
- Intravenous glycerly trinitrate (GTN)
- Unwanted effects are common; headache and postural hypotension may occur.
What are the other clinical uses of organic nitrates?
- 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 cannot tolerate more commonly used CHF drugs).
Describe the action of potassium channel activators in the treatment of angina.
Give an example.
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Nicorandil
- Combines activation of potassium K+ATP channels with nitrovasodilator actions (has a NO donation effect).
- 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.
- Combines activation of potassium K+ATP channels with nitrovasodilator actions (has a NO donation effect).
Give examples of other anti-anginals and state their mechanism of action.
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Ivabradine
- Inhibits F-type channels in the heart.
- Reduces cardiac pacemaker activity.
- Therefore inhibits heart rate.
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Ranolazine
- Unique anti-anginal used as a last resort.
What is the first-line therapy in pharmacological management of angina?
- β-blockers should be used as first-line therapy for the relief of symptoms of stable angina.
- Patients who are intolerant of β-blockers should be treated with either rate limiting calcium channel blockers, long-acting nitrates or nicorandil.
Describe drug interventions to prevent new vascular events.
- All patients with stable angina due to atherosclerotic disease should receive long-term standard aspirin and statin therapy.
- All patients with stable angina should be considered for treatment with angiotensin-converting enzyme inhibitors.
Describe combination therapy in pharmacological management of angina.
- When adequate control of anginal symptoms is not achieved with β-blockade, a calcium channel blocker should be added.
- Rate-limiting calcium channel blockers should be used with caution when combined with β-blockers.
- Patients whose symptoms are not controlled on maximum therapeutic doses of 2 drugs should be considered for referral to a cardiologist.
