Pharmacology - Myocardial Ischaemia & Antianginal agents Flashcards
Coronary Blood Flow (CBF) - 4
- Heart receives blood from two main coronary arteries: the left coronary artery, supplies most of the left side of the heart, and the right coronary artery, which supplies the right heart muscles.
- Venous blood from the heart is drained into the right atrium through the coronary sinus & anterior cardiac veins, with some blood draining directly into the chambers.
- The heart also contains collateral vessels, which are normally collapsed but can expand if there is an obstruction in the coronary arteries.
- These vessels can help bypass blocked areas, supplying blood to nearby heart muscle cells. This feature aids in maintaining blood flow to the heart during conditions like coronary artery obstruction.
CBF & Cardiac Oxygen Demand - 3
- During systole, contracting heart muscle compresses coronary arteries, limiting blood flow.
- Compensatory mechanisms cause heart rate to rise in exercise despite high heart rate reducing relaxation time
- Blood flow increase driven by metabolic or hypoxic mechanisms. As oxygen demand rises, local metabolites & hypoxia trigger dilation of coronary vessels, enhancing blood flow to supply heart with oxygen.
Hyperaemia
Hyperaemia – metabolic vasodilation of blood vessels
Cardiac myocytes: Adenosine - 2
Adenosine:
1. Produced from ATP breakdown due to increased heart rate, cardiac workload, & ATP usage in cardiac myocytes.
2. Adenosine diffuses to nearby blood vessels & acts on A2A adenosine receptors on coronary smooth muscle cells, increasing cyclic AMP (cAMP), which causes vasodilation & enhances coronary blood flow.
Smooth muscle: Adenosine -
Adenosine binds to receptors, increasing cAMP, causing vasodilation, increasing CBF
Cardiac myocytes: Adenosine
Increase heart rate, to increase cardiac workload, increasing ATP breakdown, increasing AMP binding to 5’-nucelotidase, increasing AMP
CBF: Potassium Ion Build-up - 2
- Increased Heart Rate leads to influx of potassium ions during depolarization, causing a increase in extracellular [potassium]
- Elevated potassium activates electrogenic sodium-potassium ATP channels in coronary smooth muscle cells, triggering hyperpolarization & further vasodilation, increasing CBF
Stable Angina - 3
- Coronary atherosclerosis leading to reduced blood flow.
- Triggered by exercise or stress.
- Chest pain (angina pectoris) occurs under physical exertion or emotional stress due to limited myocardial oxygen supply.
Unstable Angina - 4
- Partial occlusion of coronary vessels, often due to platelet aggregation.
- Can occur at rest & may lead to severe conditions e.g. MI (heart attack).
- Associated with either complete or partial coronary thrombosis.
- Part of ACS, which also includes MI
Variant Angina (Prinzmetal’s Angina) - 3
- Spontaneous coronary artery contraction, often occurring at rest.
- Chest pain due to transient spasm in coronary arteries.
- Requires a different treatment approach compared to stable angina, as the underlying cause is coronary artery spasm
Myocardial Ischemia - 8
- Cause of Myocardial Ischemia: Imbalance between 02 demand & supply to heart muscle leads to angina (chest pain).
- Pain ranges from dull to sharp, stabbing sensations.
- Stable angina is typically triggered by stress or physical exertion.
- Symptoms subside with rest, & pain typically resolves when heart rate & workload decrease.
Challenges in Diagnosis: - Non-specific Symptoms: e.g. fatigue shared by other conditions
- If untreated, angina can progress to more severe conditions, including heart attacks.
Therapeutic Strategy: - Focus on reducing heart rate and cardiac workload.
- Enhance coronary blood flow and improve collateral circulation.
SYMPTOMATIC TREATMENT OF STABLE ANGINA
- 1st line 2 & 2nd line 2
1st line treatment: Stable Angina - 2
1. A BETA BLOCKER e.g. Amlodipine
or
2. A CALCIUM CHANNEL BLOCKER e.g. Atenolol
Second-line treatment - 2
1.A beta-blocker + a CCB
or (if the above drugs are contraindicated)
2. LONG-LASTING ORGANIC NITRATE VASODILATORS
e.g. Nicorandil
Effects of organic Nitrates - 5
- NO acts on both veins & arteries, stronger effect on veins
- Dilates collateral blood vessels, increasing 02 supply to ischemic areas of the myocardium.
- Enhances blood flow to the heart by dilating coronary arteries.
- Reduces cardiac preload & afterload, lowering cardiac 02 demand & decreasing heart’s workload
- S/Es Organic nitrates, which release nitric oxide, can cause systemic side effects, including those related to vasodilation (e.g., hypotension).
Organic Nitrates: NICORANDIL - 6
A nicotinamide ester with a dual action:
1. Nitrate-like action (NO group)
2. Activator of vascular ATP-sensitive potassium channels (higher doses)
3. Systemic venodilatation (a decrease of cardiac preload)
4. Arteriodilatation (an increase in CBF and decrease in TPR)
5. No effect on cardiac contractility (as seen with beta-blockers)
6. S/Es dizziness, ulcerations
VARIANT (PRINZMETAL’S) ANGINA - 3
- Ischaemia & angina symptoms occur at rest due to coronary vasospasm
First choice: - NITRATE VASODILATOR + CCB (dilate coronary arteries)
- Beta-blockers are not effective
(pain is not due to increased cardiac workload)
ACUTE CORONARY SYNDROME: UNSTABLE ANGINA - 5
Symptoms:
1. Unstable chest pain occurring at rest
2. Urgent hospitalisation required
3. Causes: Ischaemia due to thrombus formation
UNSTABLE ANGINA:
4. Partial occlusion – NSTEMI
5. Complete occlusion – STEMI
Acute management of MI with STEMI - 3
- Primary Percutaneous Coronary Intervention (PCI):
Coronary angioplasty, Thrombus extraction, Stenting - Coronary Artery Bypass Grafting (CABG)
- FIBRINOLYSIS WITH ANTITHROMBIN THERAPY
PREVENTION OF SECONDARY MI - 4
- ACEi
2.Dual antiplatelet therapy - B Blockers
- Statins
