28-09-22 - Pharmacological Treatment of Angina Flashcards
Learning outcomes
- 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.
What 3 factors that shrink the window for coronary flow?
What are examples of things that can alter these 3 factors?
- 3 factors that shrink the window for coronary flow:
1) Shortening diastole e.g increase heart rate
2) Increased ventricular end diastolic pressure e.g aortic valve stenosis will cause incomplete emptying which increases ventricular pressure
3) Reduced diastolic arterial pressure e.g mitral or aortic valve incompetence (stenosis) can cause blood to go back into ventricles, which can lead to heart failure
What is coronary ischaemia usually a result of?
What does it cause?
What is sudden ischaemia usually a result of? What does it cause?
What do coronary spasms sometimes cause?
What effect can calcium overload caused by ischemia have?
- Coronary ischaemia is usually the result of atherosclerosis and causes angina
- Sudden ischaemia is usually cause by thrombosis and may result in cardiac infarction
- Coronary spasms sometimes cause variant angina
- Ischaemia can lead to a cellular calcium overload, which can cause cell death and dysrhythmias
What is Angina Pectoris?
What is it caused by?
How can it be described by patients?
What are SIGN guidelines of angina?
Typically, where is angina located?
What 3 things can it be brought on by?
What is thought to be the chemical cause of angina?
How Is angina linked to heart attacks?
- Angina pectoris is chest pain due to inadequate supply of oxygen to the heart
- Angina can be described as severe or crushing
- SIGN guidelines for angina are ‘tight, constricting, dull or heavy’
- Angina is often retrosternal, or left of the chest and can radiate to the left arm, neck, jaw and back
- Angina can be brought on by exertion, cold, or excitement
- Chemically, angina is thought to be caused by the build-up of chemical factors (e.g adenosine) due to increased metabolism of the tissue and lack of blood supply to give nutrients and take away waste products produced by this increased metabolism
- Angina can accompany or be a precursor of a heart attack
What are the 3 classifications of angina?
What are alternative names for each?
What type of ischaemia is associated with each type?
How are each of them caused?
- 3 classifications of angina:
1) Stable angina
* Aka chronic stable angina
* Stable angina is caused by demand ischaemia
* Demand ischemia is a specific type of ischemia where the oxygen requirements of the myocardium are not being met due to some increased need
* Stable angina presents with predictable pain on exertion
* It is caused by a fixed narrowing (fixed stenosis) of the coronary arteries
2) Unstable angina
* Unstable angina is caused by supply ischaemia, as it occurs at rest
* Unstable angina occurs at rest and with less exertion than stable angina
* It is associated with thrombus (blood clot) around a ruptured atheromatous plaque, but without complete occlusion of the vessel (similar to MI)
3) Variant angina
* Aka Prinzmetal variant angina
* Variant angina is caused by supply ischaemia
* It is common and caused by coronary artery spasm (vasospasms) which are random spasms of the vasculature in the heart which can block blood supply
* Not completely understood, but sometimes associated with atherosclerosis
What are 6 treatments to reduce chest pain symptoms?
What are 5 treatments to prolong survival?
- 6 treatments to reduce chest pain symptoms:
1) Beta-blockers
2) Nitrates
3) Calcium channel antagonist (Calcium Channel Blockers – CCBs)
* These 3 ^ are the most common
4) Nicorandil
5) Ivabradine
6) Ranolazine
* These 3 ^ are used as individual treatments, not extensively
- 5 treatments to prolong survival:
1) Beta-blockers
2) Aspirin
3) Statins
* These 3 ^ are used to reduce CV risk of future events occurring
4) (Angiotensin Converting Enzyme Inhibitors)
5) (Angiotensin II Receptor Blockers)
How do antianginal drugs mainly work?
What are 3 vasodilators are used to treat angina?
What structures do they work on?
How do they work to reduce angina?
What 2 medications that decrease metabolic demand of the heart are used to treat angina?
How do they do this?
- Antianginal drugs mainly work by decreasing the metabolic demand of the heart by reducing the workload of the heart
- Vasodilators used to treat angina:
1) Organic nitrates
2) Nicorandil
3) Calcium channel antagonists (Calcium channel blockers – CCB) - Vasodilators affect the arteries, veins, or both depending on the drugs and concentrations
- Vasodilators work to decrease preload, or afterload, or both in order to reduce angina
- The preload is the force that stretches the cardiac muscle prior to contraction, with greater volumes of blood providing greater stretch
- By dilating the returning veins, this increases their capacitance and lessens the volume of blood entering the heart
- Afterload is the pressure of systemic vascular resistance in the aorta that the left ventricle has to pump against in order to push blood into systemic circulation
- Dilation of the aorta will decrease total peripheral resistance, which decreases pressures in the aorta, which will decrease the afterload, which decreases the force required to move blood forwards
- 2 medications that decrease metabolic demand of the heart are used to treat angina:
1) Β-blockers
2) Ivabradine - These medications decrease metabolic demand of the heart by decreasing heart rate in order to reduce angina
What are 2 examples of organic nitrates?
How does length of onset and action compare?
What situations are they each good for?
What are organic nitrates examples of?
How do they work to reduce angina?
How do the effects of low concentrations and high concentrations of organic nitrates differ?
How can they be administered?
How do they decrease cardiac workload?
What type of angina are effects of organic nitrates particularly useful?
- Examples of organic nitrates:
1) Glyceryl trinitrate – rapid onset, short acting, good for immediate relief
2) Isosorbide mononitrate – slow onset, longer acting, good for anticipating angina e.g before exercise - Organic nitrates are examples of powerful vasodilators which reduce the effects of angina
- Organic nitrates work by being metabolised to nitric oxide (also released by endothelial cells to cause relaxation) to relax smooth muscle, particularly vascular smooth muscle
- They predominantly act on veins to reduce cardiac preload
- Lower concentrations are normally given as tablets or sprays
- Higher concentrations delivered intravenously can also after arteries, therefore also decreasing afterload
- If collateral coronary vessels are dilated by organic nitrates, this can decrease cardiac workload, as this improves distribution of coronary blood flow towards ischaemic areas
- Dilation of constricted coronary vessels is particularly beneficial in variant angina
What 2 types of anginas are organic nitrates used to treat?
How is this done?
What are 3 unwanted side effects of organic nitrates?
What are 2 other clinical used of organic nitrates?
- Organic nitrates can be used to treat:
1) Stable angina
* Prevention by glyceryl trinitrate (rapid onset, short acting, good for immediate relief) shortly before
* Prevention by isosorbide mononitrate (slow onset, longer acting, good for anticipating angina e.g before exercise) long before
2) Unstable angina
* Intravenous glyceryl trinitrate (GTN) will reduce afterload and preload
* Dilation of constricted coronary vessels is particularly beneficial in variant angina
- 3 unwanted side effects of organic nitrates:
1) Unwanted effects are common
2) Headache
3) Postural hypotension - 2 other clinical uses of organic nitrates:
1) Acute heart failure in specific circumstances
* Intravenous GTN
2) Chronic heart failure (CHF)
* isosorbide mononitrate with hydralazine in patients of African American origin especially, (or patient cannot tolerate more commonly used CHF drugs)
What are β-blockers used for in terms of angina?
What 2 anginas does it work on?
How do beta blockers work?
How can beta blockers decrease rates of death after MI?
What are 2 examples of Beta-blockers?
- Β-blockers are first line treatment in the prophylaxis (prevention) and treatment of stable and unstable angina
- It can also be used to increase life span
- Beta blockers decrease the metabolic demands of the heart by decreasing cardiac oxygen consumption and unstable angina
- Beta-blockers have an antidysrhythmic action, which reduces the rate of deaths after MI
- Examples of beta-blockers:
1) Bisoprolol
2) Atenolol
How do Calcium Channel Blockers (CCB) work?
What do CCBS mainly affect?
What are the 2 main types of CCBs?
What are 2 examples of each?
Are CCBs vasodilators or vasoconstrictors?
What do they mainly effect?
How do dihydropyridine and rate limiting CCBs effects differ?
- Calcium Channel Blockers (CCB) work by orienting the opening of voltage-gated L-type Ca2+ channels, which blocks Ca2+ entry
- CBBs mainly affect the heart and smooth muscles to inhibit calcium entry upon muscle cell depolarisation
- Two main types of CCBs:
1) Dihydropyridine derivatives e.g amlodipine and lercanidipine
2) Rate-limiting e.g verapamil and diltiazem - CBBs are vasodilators
- CCBs vasodilator effect mainly affects smooth muscle resistances vessels (e.g arterioles), which causes total peripheral resistance to drop, which reduces afterload.
- They also dilate coronary vessels, which is especially important in variant angina
- Dihydropyridine derivative CCBs tend to just affect arterial smooth muscle in resistance vessels
- Rate limiting CCBs can also reduce and impair AV conduction, which can influence heart rate and myocardial contractility
What dictates the choice of CBBs used in cases of angina?
When is each type of CCB used?
When might these medications not be used?
What are 3 side effects of CCBs?
- The choice of CCB used depends on comorbidity and drug interactions
- When each type of CBBs are used in cases of angina:
1) Dihydropyridine derivatives
* E.g amlodipine and lercanidipine
* Safe in patients with heart failure
* Used alongside beta-blockers in most angina
* Used instead of a Beta-Blocker in Prinzmetal angina
* Use of dihydropyridines means we reduce the interaction with other medications we want to add on
2) Rate limiting CCBs
* e.g verapamil and diltiazem
* Used but contraindicated (should not be used) in heart failure, bradycardia, AV block or in presence of Beta-Blocker
- Side effects of CCBs:
1) Headache
2) Constipation
3) Ankle oedema
What are 2 other clinical used of CCBs? What types of CCBs are used?
How do they work?
- 2 other clinical used of CCBs:
1) Antidysrhythmics
* Mainly verapamil used (rate-limiting CCB)
* Slows ventricular rate in rapid atrial fibrillation
* Prevents recurrence of supraventricular tachycardia (SVT)
* No effect on ventricular arrhythmias
* Will only affect what’s happening in terms of SA node to AV node conduction part of the pathway
2) Hypertension
* Mainly amlodipine or lercanidipine (dihydropyridines derivatives)
* CCBs can be use as hypertension, but it tends to be a disorder of the vasculature, which changes the tone of the vasculature
What is an example of potassium channel activators?
Are they arterial or venous dilators?
How do they work?
How does this lead to a reduction in preload and afterload?
What 3 symptoms do potassium channel activators cause?
When are potassium channel activators used?
- Nicorandil is an example of potassium channel activators
- Potassium channel activators are arterial and venous dilators
- Potassium channel dilators work by combining the activation of K+ ATP channels with nitrovasodilator actions from Nitric oxide (NO)
- This causes hyperpolarisation of vascular smooth muscle
- This hyperpolarisation decreases the activity/sensitivity of vascular smooth muscles in both the arterial and venous sides
- This leads to a reduction in preload (primarily by NO donating effects dilating veins) and afterload (we decrease the ability of vascular smooth muscles to depolarise by making them less sensitive through hyperpolarisation, leading to decreased constriction of arterioles, decreased systemic pressures, and decreased afterload)
- 3 symptoms do potassium channel activators cause:
1) Headaches
2) Flushing
3) Dizziness - Potassium channel activators are used for patients who remain symptomatic despite optimal management with other drugs, as high doses can affect the excitability of cardiac tissue
What are 2 other uncommon anti-anginals? How do they work?
- 2 other uncommon anti-anginals:
1) Ivabradine
* Inhibits funny f-type Na+ channels in the heart
* Reduces the pacemaker activity, therefor decreases the heart rate
* Similar to the effect of beta-blockers, but more specific on rate than influencing contractility
2) Ranozaline
* Unique anti-anginal used as a last resort
* Mechanism very complicated
