L17- drug treatments of cardiovascular disease

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drug treatments of cardiovascular diseases
Rose P
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Rose P
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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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