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| Question | Answer |
| Major cardiovascular diseases | -hypertension- high blood pressure - angina- temporary cardiac pain, usually on exercise - myocardial infarction- sustained cardiac pain and cell death due to coronary thrombosis - arrythmias- lack of normal heart rythm - heart failure- insufficient cardiac output to meet the body's needs |
| The cardiovascular disease continuum: the range of cardiovascular diseases and how they develop | |
| Atherosclerosis and risk factors | Atherosclerosis- build up of plaque in the arteries. Rupturing of which causes thrombosis. - Coronary heart disease results from atherosclerosis as the build up of plaque causes stenosis (narrowing of the arteries). - stenosis consists of a cholesterol core surrounded by a fibrous cap - Risk factors: - High LDL - Smoking - Obesity - Diabetes - Male gender - Age - Family history |
| Atherogenesis; the build up to atherosclerosis | 1. fatty streak forms; macrophages enter the wall of the artery. These accumulate lipids; begins in early life. - Occurs in everyone, but only develops into a problem for some. 2. Atherosclerotic plaque- can cause angina or rupture to form a thrombosis. |
| Angina | - fairly common, 2million ppl in the UK living with it - Characterised by a temporary squeezing/crushing sensation/chest pain - most common form is stable angina (angina of effort), triggered by excitement/exertion. - Results from an increase in demand of oxygen from the heart, but restricted blood flow. - Growth of coronary collaterals help to reduce the severity of the angina; SOME people grow these and it helps the blow throgh through other coronary arteries |
| Angina treatment: aims | Using drugs: - main aim is to reduce cardiac workload and oxygen demand - secondary aim is to increase supply to ischaemic zone by dilating coronary arteries. (doesnt work in everyone) Using surgery: - increasing O2 supply through opening up arteries using percutaneous coronary intervention (PCI) or bypass surgery |
| Sites of action of drugs that treat angina | Reducing the cardiac load, done by reducing the following factors: - Preload; central venous pressure, cardiac stretch - Afterload; arterial pressure and TPR - Contractility; stimulation of B receptors - heart rate; b receptors and m receptors |
| Drugs used to treat angina | - B blockers- reduce heart rate and force, reducing cardiac workload and demand for oxygen - Ivabradine; reduces heart beat, heart spends more time in diastole, fills with more blood. - Calcium channel blockers - Nicorandiel The above reduce afterload (TPR), therefore reducing workload and O2 demand. - Organic nitrates- reduce preload, which reduce workload and O2 demand - Ranolazine- reduces cardiac stiffness and therefore workload and O2 demand |
| Organic nitrates in their treatment of angina | Organic nitrates have been used for over 100 years to treat angina - contain nitrate groups that are metabolised to produce nitric oxide - nitric oxide is a good vasodilator, reducing preload, which in turn reduces cardiac output and thus cardiac load. This is called the "Frank Starling law". - Work very fast, under a minute. |
| Surgical treatment of angina | - Coronary artery bypass grafting (CARBG), bypasses stenosis ^ tends to be used in very serious disease, where there is plaque in all 3 arteries- triple bypass surgery - Percutaneous coronary intervention (PCI), angioplasty ^ less serious cases, balloon passed uninflated into coronary artery, positioned across the stenosis then inflated to open up the stenosis. Then, a stent is entered to hold the artery open and in place. |
| Myocardial infarction | - death of myocardial tissue - 90,000 die per year of this in the UK - Results from coronary thrombosis (rupturing of plaque in coronary artery causing platelet aggregation and blood coagulation cascade followed by a blood clot in the vessel, resulting in regional ischemia (progressive cardiac cell death)) |
| Consequences and treatment of severe myocardial ischemia | Consequences: arrythmias- 25% of people die from VF. Defib cn be used in an attempt to get the heart back in normal rythm. If there is severe pain morphine can be used. - Poor contractility leads to cardiac cell death- cells take up to 12 hours to die so removing thrombus before then gives time to save cardiac cells. - PCI (balloon stent) can also be used |
| Drugs used to treat myocardial ischemia | - Thrombolytic drugs eg: altepase. Breaks down thrombosis causing the blockage by breaking down fibrin network in the blood clot. - Antiplatelet drugs eh: aspirin and ticagrelor; inhibit further platelet aggregation. ^ aspirin also inibits the binding of the pro-aggregatory factor ADP to it's receptor on platelets * Myocardial ischemia can be treated long-term with b-blockers, statins, ACE-inhibitors etc to reduce the chance of another MI and chronic heart failiure. |
| Chronic heart failiure | - Chronic heart failiure occurs when cardiac output is too low to perfuse tissues adequately (due to abnormally low contractility). - Can result from MI, hypertension etc - Leads to oedema, breathlessness, and 'cardiac remodelling'; an enlarged but weaker heart. |
| Drug treatment of chronic heart failiure | Long term: aim to decrease progressive cardiac remodelling and symptoms.: - ACE inhibitors or angiotensin receptor blockers (ABS)-- slow cardiac remodelling and decrease TPR - Beta blockers-- decrease sympathetic stimulation of the heart, slow cardiac remodelling, work on B receptors - Aldosterone antagonists- slow cardiac remodelling -Valsartan/sacubutril ARB plus a neprilysin inhibitor. Neprilysin is an endopeptidase that breaks down the peptide ANP, having anti-remodelling effects. Drugs taken with the above: - diuretics to reduce oedema - digoxin- a positive inotrophic drug (strengthens heart contractions). |
| Drug treatment for acute heart failiure | - Use short term inotrophic support. - B1 adrenoreceptor agonists keep patient alive by increasing heart beat. |
| Treatment of Arrythmias | - Defib for VF - Drugs - destruction of the site of ectopic impulse generation or implant pacemaker |
| Hypertension | - incidence increases with age - General definition= Systolic: >140/>100 - major risk factor for atheroclerosis (coronary heart disease) |
| Hypertension treatment: lifestyle changes | - lose weight if overweight/obese - eat less salt - take more exercise |
| Drug treatment of hypertension | - the causes of primary hypertension are unknown - in the long-term, BP is controlled by the kidneys: 1. defective kidney function leads to an increase in blood pressure 2. this results in an increase in blood volume, resulting in increased cardiac output, resulting in increased bp. *treated using diuretics* can also result from ANS overractivity: 1. increased vasoconstriction 2. leads to increased TPR 3. resulting in an increase in bp *can be treated using vasodilators *drugs that inhibit the renin-angiotensin system are both diuretics and vasodilators* |
| Examples of reninangiotensin system (RAS) inhibitors | - ACE inhibitors - ARBS - (less so) b-blockers - aldosterone antagonists - renin antagonists - calcium channel blockers -thiazide-type diuretics - a-blockers -K+ channel agonists - no single type of hypertensive drug works in >60% of people, most use several simultaneously |
| General strategies to reduce the risk of cardiovascular disease and MI | - healthier lifestyle - stopping smoking - replacing saturated fat with unsaturated, eating less sugar - do more exercise - eat less salt - take omega-3 - Long-term drugs: - statins to lower LDL cholesterol by reducing synthesis of ldl cholesterol in the liver. eg atorvastatin - low dose aspirin to reduce risk of thrombosis |
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