L19 Drug Treatment Of Cardiovascular Diseases

Front 1

What are the cardiovascular diseases drugs are useful in treating?

Back 1

hypertension:high blood pressure

angina:temporary cardiac pain, usually on exercise

myocardialinfarction: sustainedcardiac pain and cell death due to coronary thrombosis arrhythmias:lack of normal heart rhythm

heartfailure: insufficient cardiac output to meet body’s needs

Front 2

What are some risk factors in cardiovascular disease?

Back 2

High LDL

Smoking

Obesity

Diabetes

Male gender

Age

Family history

Front 3

What can Vasculardysfunction lead to?

Back 3

Atherosclerosis,

Hypertension

Front 4

What does atherosclerosis directly lead to?

Back 4

Angina,

Thrombosis

Front 5

What does Hypertension lead to?

Back 5

Stroke,

Heart failure

Front 6

What else causes a stroke?

Back 6

Thrombosis

Front 7

What else do Thrombosis lead to?

Back 7

Acute MI

Front 8

What does an acute MI lead to?

Back 8

Heart failure ----> Arrhythmias and sudden cardiac death

Front 9

What is atherosclerosis?

Back 9

Coronaryheart disease results from atherosclerosis - thebuild-up of cholesterol-rich plaques, causing a stenosis (narrowing) of the arteries

Front 10

What type of process is atherogenesis?

Back 10

Atherogenesis: a progressive process

Fattystreak ----> Atherosclerotic plaque ----> Plaque ruptureandthrombosis

Front 11

What are acute coronary syndromes precipitated by?

Back 11

‘Acutecoronary syndromes’precipitatedby sudden ↓in coronary flow

Front 12

What does thrombosis cause?

Back 12

unstableangina

NonST segment elevation MI

STsegment elevation MI

Front 13

What does the stable plaque lead to?

Back 13

vasoconstriction, spasm ----> loss of coronary flowreserve → stable angina

Precipitated by an ↑inmyocardial O2 demand

Front 14

What are the main risk factors in athersclerosis?

Back 14

Highplasma cholesterol(>5 mM)

smoking

diabetes

Age, male gender, family history

HYPERTENSION

Front 15

What is angina caused by?

Back 15

Affects~ 2m people in UK

•temporary squeezing sensation orpain in chest

•most common form = stableangina (angina of effort)

•triggered by excitement or exertion

•results from ­ cardiac O2demand with restricted blood flow

Front 16

What helps to reduce angina?

Back 16

Growthof coronary collaterals helps to reduce the severity of angina

Front 17

What is the drug treatment for angina?

Back 17

• ­ ↑O2 supply to ischaemic zone by dilating coronary arteries (mainly collateral arteries will dilate)

•↓Cardiac workload and O2 demand = main treatment strategy

Front 18

What is the surgical treatment for angina?

Back 18

Using surgery

• ↑O2 supply: open up arteries using percutaneous coronary intervention (PCI) or bypass surgery

Front 19

What is Cardiacworkload determined by?

Back 19

preload: central venous pressure

afterload: arterial pressure and TPRcontractility: stimulation of b-receptorsheart rate

Front 20

What do organic nitrates do?

Back 20

Organicnitrates: decreased preload, so decreased workload and O2 demand

Front 21

What do B-blockers do?

Back 21

•b-blockers: decreased HR and force, so decreased cardiac workload and demand for O2

•Ivabradine: decreased HR

Front 22

What do Ca2+ channel blockers do?

Back 22

•Ca2+ channel blockers

•Nicorandil decreased TPR (afterload), so decreased workload and O2 demand

Front 23

How do nitrates decrease workload?

Back 23

• nitrates relax veins mainly, so ↓ venous pressure

• ↓ “preload” (stretch of heart musclebefore the next beat), so decreased cardiac output (Starling)

• so, ↓ workload+ O2demand of heart

Front 24

What do organicnitrates cause?

Back 24

NO ---> veinsdilate ----> ↓ cardiac work

---->coronarycollateralsdilate

Front 25

What is the Surgical treatment of angina?

Back 25

Coronaryartery bypass grafting (CABG)

Percutaneouscoronary intervention (PCI), angioplasty

Front 26

What is a myocardial infarction?

Back 26

infarction = deathof myocardial tissue

Front 27

What does MI result from?

Back 27

MIresults from coronary thrombosis

Front 28

What happens in coronary thrombosis?

Back 28

rupture of atherosclerotic plaque in coronary artery

-----> platelet aggregation + bloodcoagulation

-----> formation of thrombus (clot insidevessel)

-----> regional ischaemia

------> cardiac cell death (myocardial infarction, MI) in a few hours

Front 29

What are the consequences and treatment of severe myocardial ischaemia?

Back 29

Arrhythmias

•about25% of people die from ventricular fibrillation (VF)

•use defibrillator if VF occurs

Severe pain (usually)

•givemorphine or diamorphine i.v.

Poor contractility and then cardiac cell death

•cellstake up to 12 hours to die; removing the thrombus duringthis time can save cardiaccells (and thus patients’ lives!).

Front 30

What is Emergencycoronary reperfusion?

Back 30

•PerformPCI asap

•Use athrombolytic drug i.v. (e.g. alteplase) to break down the thrombus thatis causing the blockage: works by breaking down the fibrin network in the bloodclot

•Alsogive antiplatelet drugs,

e.g. aspirin plus clopidogrel, which inhibit further plateletaggregation:-

aspirin inhibits COX, the enzyme thatproduces the pro-aggregatory factor, thromboxane A2 (TXA2)

-clopidogrel inhibits the binding of thepro-aggregatory factor, ADP, to its receptor on platelets

Front 31

What is CHRONIC HEART FAILURE?

Back 31

When cardiac output is too low to perfuse tissues adequately (due toabnormally-low contractility)

•can result from MI, hypertension,etc.

•leads to oedema, breathlessness and ’cardiacremodelling’ an enlarged but weaker heart

Front 32

What is the short term blood loss?

Back 32

Front 33

What are the long term effects of heart failure?

Back 33

↓ ↓ cardiac output

pulmonary oedema arrhythmias

cardiac remodelling

Front 34

What are the long term treatments of heart failure?

Back 34

Long-term: aim to decrease progressivecardiac remodelling and symptoms:

•ACE inhibitors or angiotensin receptor blockers, ARBs (slow cardiacremodelling, decreaseTPR)

• b-blockers (decrease symp. stimulation of heart, slow cardiac remodelling)

•Aldosterone antagonists (slow cardiac remodelling)Plus

•diuretics (reduce oedema)

•digoxin (positive inotropic drug)

Front 35

What is Acute(short-term) inotropic support in severe HF?

Back 35

b1-adrenoceptoragonists to keep patient alive

e.g. dobutamine

Front 36

How are arrhythmias treated?

Back 36

Treat with:

•defibrillator for VF

•drugs (see previous lecture)

•surgery to destroy ectopic site ofimpulse generation (radiocatheter ablation), or to implant pacemaker

Front 37

What is bp determined by?

Back 37

BP =CO x TPR

Front 38

What is the general definition of hypertension?

Back 38

General definition: if BP > 140 / 100 mm Hg = systolicBP / diastolic BP

Front 39

Why do we need to treat hypertension?

Back 39

•Need to treat, as is major riskfactor for:–atherosclerosis (causes coronary heart disease)–stroke (can burst a cerebral artery)

Front 40

What lifestyle changes can help?

Back 40

•Lifestyle changes help:

–lose weight if overweight/obese

–eat less salt

–take exercise–change job!

Front 41

What are the causes of primary hypertension?

Back 41

Thecauses of primary hypertension (the most common type) are unknown.

Inthe long term, BP is controlled by the kidneys (Guyton hypothesis)… and perhapsbythe ANS acting to regulate vascular tone and TPR (neurogenic hypothesis)

Front 42

Is a single drug used in most people?

Back 42

Nosingle type of anti-hypertensive drug works in >60% of people…Mostpeople must use several of these drugs simultaneously

Front 43

What are the Generalstrategies to reduce risk of CV disease and MI?

Back 43

Healthier lifestyle

•stop smoking

•replace saturated fats in diet with polyunsaturated & monounsaturated fats and eat lesssugar (diabetes →coronary heart disease)

•do more exercise

•take: omega-3 fish oils, alcohol,antioxidants ????

Give drugs long-term, e.g.:

•statins, e.g. simvastatin, to reduce plasma cholesterol by ↓ synthesis of cholesterol in liver•low-dose aspirin to reduce risk of thrombosis