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L17- drug treatments of cardiovascular disease
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- 1Major 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 - 2The cardiovascular disease continuum: the range of cardiovascular diseases and how they develop
- 3Atherosclerosis and risk factorsAtherosclerosis- 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 - 4Atherogenesis; the build up to atherosclerosis1. 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.
- 5Angina- 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 - 6Angina treatment: aimsUsing 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 - 7Sites of action of drugs that treat anginaReducing 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 - 8Drugs 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 - 9Organic nitrates in their treatment of anginaOrganic 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. - 10Surgical 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. - 11Myocardial 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)) - 12Consequences and treatment of severe myocardial ischemiaConsequences: 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 - 13Drugs 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. - 14Chronic 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. - 15Drug treatment of chronic heart failiureLong 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). - 16Drug treatment for acute heart failiure- Use short term inotrophic support.
- B1 adrenoreceptor agonists keep patient alive by increasing heart beat. - 17Treatment of Arrythmias- Defib for VF
- Drugs
- destruction of the site of ectopic impulse generation or implant pacemaker - 18Hypertension- incidence increases with age
- General definition=
Systolic: >140/>100
- major risk factor for atheroclerosis (coronary heart disease) - 19Hypertension treatment: lifestyle changes- lose weight if overweight/obese
- eat less salt
- take more exercise - 20Drug 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* - 21Examples 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 - 22General 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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- drug treatments of cardiovascular diseases
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- Rose P
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