Angina & Hypertension Drugs PDF

Angina and hypertension drugs L.O’s 1-describe the pathophysiological basis of stable angina 2-list the drugs used to help manage stable angina 3-describe how the mechanism of action of anti-anginal drugs is linked to understanding of the pathophysiology of stable angina -​ Myocardial oxygen...

Angina and hypertension drugs L.O’s 1-describe the pathophysiological basis of stable angina 2-list the drugs used to help manage stable angina 3-describe how the mechanism of action of anti-anginal drugs is linked to understanding of the pathophysiology of stable angina -​ Myocardial oxygen demand : It is how much oxygen the myocardium needs to function properly -​ Myocardial perfusion happens during diastole : The myocardium is only perfused with oxygenated blood during diastole ; it is because during systole the high intraventricular pressure compresses the coronary arteries limiting blood flow -​ Oxygen demand and the heart workload : The workload is influenced by : HR - faster heart rate = less diastolic time and inc. o2 demand Ventricular wall tension - the pressure and volume inside the ventricles affects how much force the heart must generate Wall thickness - a thicker myocardium requires more o2 Conditions like hypertension, tachycardia, and left ventricular hypertrophy increase MVO₂, leading to angina if coronary blood flow is insufficient. Beta-blockers reduce heart rate, lowering oxygen demand, which is why they are used in angina management. -​ Normal coronary arteries : Coronary blood flow i linked to oxygen demand a the myocardium requires continuous supply of oxygen to function and the CBF is adjusted to meet this demand Resting coronary flow is 225 ml/min Vigorous coronary flow is 800+ ml/min to meet higher oxygen demands Compromised coronary flow leads to ischemia : if the coronary arteries cannot deliver enough oxygenated blood due to blockages (atherosclerosis) it results in ischaemia This can cause angina or lead to myocardial infarction Patients with coronary artery disease (CAD) have reduced coronary reserve, meaning they struggle to increase blood flow during exertion, leading to exertional angina. Interventions like coronary angioplasty or bypass surgery help restore adequate blood flow to ischaemic areas. -​ Arterial stiffness : Normal arterial elasticity and blood flow : in a healthy CV system arteries are elastic and they expand in response to pulsatile ejections of blood from the heart , this elasticity helps dampen the pressure surge from each heartbeat and maintains steady flow during diastole Age and risk factors : with age and certain risk factors like hypertension , diabetes , smoking and high cholesterol arteries lose their elasticity and become stiffer , rigid arteries cannot expand properly leading to higher resistance (afterload) against which the heart must pump Compensatory mechanisms and cardiac impact : the heart compensates by increasing inotropy to maintain adequate blood pressure and perfusion Overtime this might lead to hypertrophy , LVH A hypertrophied heart requires more oxygen due to its increased muscle mass. If coronary arteries cannot meet this demand, myocardial ischaemia (oxygen deprivation) occurs, increasing the risk of angina, heart failure, and myocardial infarction (heart attack). -​ Atherosclerosis : The accumulation of LDL cholesterol plaques in the sub-endo of the arteries This narrows the arterial lumen restricting blood flow Pathophysiology : LDL enters the arterial lumen and becomes oxidised triggering an inflammatory response , then macrophages engulf oxidised LDL and transform inti foam cells forming a fatty streak , overtime smooth muscle proliferation and fibrous cap formation stabilise the plaque If the plaque ruptures it can cause thrombosis leading to a heart attack or stroke Consequences of atherosclerosis : Reduced oxygen of tissues : CAs = Myocardial ischaemia (angina,heart attack) Carotid/cerebral arteries = stroke or transient ischaemic attack Peripheral arteries = PAD (ulcers,gangrene) Hypertension = narrowed arteries increase vascular resistance leading to HBP -​ Myocardial ischaemia : Occurs when oxygenated blood supply to the heart fails to meet its the myocardial o2 demand Occurs due to partial or complete obstruction of coronary arteries by atherosclerosis or thrombosis Pathophysiology : stenosis reduces blood flow to the downstream myocardial tissue , O2 supply is inadequate forcing myocardial cells to switch to anaerobic glycolysis for ATP production  This leads to the accumulation of lactate which lowers intracellular pH and contributes to angina Stable angina : chest pain on exertion due to transient ischaemia with high risk of progression to myocardial infarction Unstable angina : more severe ischaemia occurring even at rest with high risk of progression to myocardial infarction Acute management of ischaemia/angina : 1- nitrates : they dilate coronary arteries and reduce myocardial oxygen demand 2- beta blockers and calcium channel blockers : they lower the heart rate and contractility reducing oxygen demand 3-antiplatelets (aspirin) : preventing clot formation For long term prevention : steroids : lower LDL cholesterol , slowing plaque formation -​ Risk factors for cardiovascular diseases : Modifiable RFs : obesity(Excess weight contributes to hypertension, dyslipidemia), smoking(Increases oxidative stress), physical inactivity, psychosocial stress (increases cortisol levels) Non-modifiable : Family history of CAD , age , kidney disease (Chronic kidney disease (CKD) accelerates atherosclerosis and increases cardiovascular mortality.) Metabolic and vascular risk factors : Hypercholesterolaemia : high LDL contributes to atherosclerotic plaque formation Hypertension : increased arterial pressure damages blood vessels and raises myocardial oxygen demand Diabetes : hyperglycemia leads to endothelial dysfunction, leading ti and increased atherosclerosis risk -​ Stable angina : predictable chest pain that occurs when the myocardial oxygen demand exceeds supply typically due to coronary arteries stenosis from atherosclerosis The narrowing limits blood flow during exertion but remains sufficient at rest Symptoms : chest pain - often describes as crushing , burning or tight , radiation - pain may spread to the left arm , jaw , or back , SOB , nausea , sweating Its triggered by : physical exertion or emotional stress both increase myocardial oxygen demand Relieved by : rest or nitroglycerin (GTN spray)  -​ Acute coronary syndrome : refers to a spectrum conditions caused by sudden reduced blood flow to the heart due to coronary artery obstruction Symptoms occurs at rest and are usually due to plaque ruptures and thrombosis Pathophysiology : Unstable atherosclerosis plaques can rupture exposing underlying collagen and tissue factor This triggers platelet aggregation and clot formation , blocking coronary blood flow The degree of obstruction determines the severity of of ACS -​ ECG : ST depression ST depression refers to a downward shift of the ST segment from the baseline on an ECG , it is a sign of subendocardial ischaemia meaning inner layer of the myocardium is not receiving enough oxygen ST depression during exercise suggests coronary artery disease as narrowed arteries cannot increase blood supply to meet the heart’s demand When myocardial oxygen demand exceeds supply ischaemia occurs leading to ECG changes -​ Coronary angiography : Diagnostic imaging technique used to visualise coronary arteries It helps detecting stenosis or occlusion Procedure : a catheter is inserted into a major artery usually femoral or radial , its guided towards the coronary arteries , then contrast dye is injected to outline the lumen of the arteries on X-ray Areas of narrowing or blockage appear as regions with absent or reduced contrast flow  The left anterior descending (LAD) artery shows partial occlusion (circled in yellow). -​ Echocardiography Non-invasive ultrasound imaging technique used to visualise the hearts structure and function It uses high frequency sound waves to create real time images of the heart It helps with assessing the heart chambers size, valve function , and wall motion abnormalities It is used clinically to detect wal motion abnormalities in CAD due to myocardial ischaemia or infarction In heart failure it is used to measure ejection fraction to assess LV function It is also used to check pericardial effusion to identify fluid accumulation around the heart -​ How can drugs help ? Drugs are used either to relieve acute symptoms or prevent future episodes Acute episodes of exertional angina can be relieved by vasodilators Example : glyceryl trinitrate (GTN spray) Acts rapidly by dilating coronary arteries Reduces preload and afterload decreasing myocardial oxygen demand Prophylactic treatment - example : beta blockers - bisoprolol Reduces heart rate and contractility decreasing myocardial oxygen demand Helps prevent ischaemic episodes during exertion or stress  -​ Organic nitrates E.g, glyceryl trinitrate, they are used for the relief of angina symptoms They act by NO which is a potent vasodilator Mechanism : GTN is absorbed into circulation and converted into NO NO activates soluble guanylate cyclase increasing cycling GMP levels cGMP induces smooth muscle relaxation by : Increasing potassium efflux leading top hyperpolarisation Reducing intracellular calcium conc. Decreasing contraction Activating myosin light chain phosphatase leading to dephosphorylation of MLC preventing contraction NO Activates Soluble Guanylate Cyclase (sGC) -​ Think of soluble guanylate cyclase (sGC) as a "switch" inside muscle cells. -​ NO flips this switch ON, and this makes the enzyme sGC produce more cGMP (cyclic GMP). Now that we have more cGMP, it works like a master key that unlocks relaxation in three main ways: Increases Potassium (K⁺) Efflux → Hyperpolarization ​ More potassium ions (K⁺) leave the muscle cells. ​ This makes the inside of the cell more negative (hyperpolarized). ​ A negative cell = less likely to contract, so the muscle relaxes. Reduces Intracellular Calcium (Ca²⁺) → Less Contraction ​ Muscles need calcium (Ca²⁺) to contract. ​ cGMP blocks calcium from entering the muscle cells. ​ Less calcium = weaker contractions → More relaxation. Activates Myosin Light Chain Phosphatase (MLCP) → Prevents Contraction  ​ Myosin is the "motor" that makes muscles contract. ​ To work, myosin needs a phosphate group (P) attached. ​ MLC phosphatase removes this phosphate (dephosphorylation). ​ Without phosphate, myosin can’t work, so the muscle stays relaxed. GTN → NO → More cGMP → Muscle Relaxation → Wider Blood Vessels → Less Work for the Heart → No Angina -​ Beta blockers aka bisoprolol They help preventing angina attacks by reducing workload Beta blockers are drugs that blocks beta adrenoreceptors in the heart Bisoprolol is a B1 selective beta blocker meaning it mainly affects the heart rather than the lungs Used to reduce heart rate contractility and overall workload on the heart How do beta blockers work ? the SNS releases adrenaline which binds to B1 adrenoceptors on the heart This activates a pathway that increases cAMP - leading to increased heart rate and stronger contractions ]beta blockers competitively inhibit B1 receptors preventing this response -​ Ca channels blockers Particularly diltiazem - they block L-type calcium channels in the heart and blood vessels This reduces calcium entry into channels Leading to weaker heart contractions (negative inotropy) Slower heart rate (negative chronotropy) Vasodilation How do CCDas work The heart needs Ca to contract , blocking Ca channels means less forceful contractions reducing the heart’s oxygen demand CCBs reduce heart workload by lowering heart rate and contractility  They also dilate coronary arteries increasing blood flow to the heart -​ Alternative drugs : 1- nicorandil - a coronary vasodilator It dilates blood vessels in two key ways -​ Stimulates guanylyl cyclase - increases cGMP -​ Increased cGMP leads to reduced Ca entry into vascular smooth muscle -​ Less Ca = more muscle relaxation = vasodilation -​ This reduces afterload (the force against which the heart pumps) improving blood flow to the heart -​ Activates K ATP channels = hyperpolarisation , this opens K channels allowing it to leave smooth muscle cells , this makes the cells hyperpolarised meaning they become less excitable -​ As a result calcium channels remains closed preventing further contraction 2- Ivabradine : HR limiter -​ Reduces heart rate without affecting contractility -​ Inhibits the “funny current” (If) in the SA node : the SA node controls heart rate -​ The funny current is responsible for slow depolarisation in pacemaker cells setting the heart rhythm’s -​ Ivabradine selectively blocks the sodium potassium current slowing down depolarisation ✔️ Nicorandil helps by dilating arteries and veins, reducing heart workload. ✔️ Ivabradine helps by slowing heart rate, reducing oxygen demand. ✔️ Both drugs are alternatives for patients who can’t tolerate beta-blockers or calcium channel blockers.