Chronic Stable Angina - 126 Flashcards
Define stable angina
Predictable - symptoms brought on by exertion and stops within minutes when exertion ceases.
Define Angina
Chest Pain or pressure caused by activities that increase myocardial O2 demand. Pain caused by metabolic acidosis.
Define unstable Angina
Unpredictable - symptoms come on at rest - acute coronary syndrome.
Define class 1 and class 4 angina
Class 1 only comes on during strenuous physical activity
Class 4 comes on at rest
What causes myocardial ischaemia?
Insufficient supply - coronary atheroma (fatty lumps inside lining of artery walls) causes a fixed reduction in maximum supply and ischaemia develops at times of high demand.
Over-demand - eg aortic stenosis, hypertrophic cardiomyopathy, hypertension.
What are the risk factors for angina?
smoking, diet (high in fat/low in antioxidants), hypertension
also family history, hyperlipidaemia, diabetes mellitus, obesity, sedentary lifestyle, age and M>F
What are the symptoms of angina?
Retrosternal crushing pain, radiates (jaw, arms, back, neck), Stops within minutes of exertion stopping, shortness of breath
What are the differential diagnosis for angina?
Reflux oesophagitis, PE, pneumothorax, aortic disection, costochondral pain, pleuritis, varicella zoster.
what investigations should be carried out on a patient with suspected angina?
ECG (at rest and on exercise stress test - ischaemia shows as ST depression), blood profile, echocardiography (sonogram to show ventricular function and damage), perfusion scintiscan (radioisotopes injected to find stenosis and asses perfusion), Angiography (assess revascularisation - v. invasive)
how should angina be managed?
1) lifestyle modification - exercise, smoking, drinking, diet
2) Medical therapy - drugs & treat underlying diseases like diabetes, hypertension, hyperlipidaemia
3) Revascularisation - Percutaneous Coronary Intervention (PCI) (balloon dilatation & bare metal/ drug eluting stents), Coronary Artery Bypass Graft (CABG)
What pharmacological options are available for the management of angina?
1) Reduce demand on heart - Beta Blockers eg atenolol or metoprolol (reduce HR and contractability), Nitrates eg GTN (vasodilator via NO), CA2+ Channel Blockers eg amlodopine (vasodilator), Nicorandil (K+ channel blocker - donates NO = dilator)
2) Reduce plaque - Statins
3) Inhibit thrombosis - aspirin & clopidogrel
What are the mechanisms for cell injury due to hypoxia
Reduction in ATP (influx of CA2+ & efflux of K+), membrane damage, O2 derived free radicals.
What is the structure of atheromatous plaques?
Core - lipid (cholesterol)
Fibrous cap - collagen, elastin, smooth muscle cells & proteoglycan stroma
Shoulder zone (inbetween) - T lymphocytes & macrophages
stable plaques are concentric, rich in stroma and smooth muscle
unstable plaques are accentric, rich in lipid & macrophages, inflammed and have endothelial cell injury.
what does darcy’s law for laminar flow state?
perfusion = pressure difference / resistance
resistance proportional to viscosity and length. inversely proportional to radius (R = 8 x viscosity x l / pi x r^4)
how is transient turbulent flow heard on auscultation?
murmur
how is turbulent flow heard on auscultation?
bruit
Vessel resistance occurs due to friction between fluid layers, how does this happen?
parabolic distribution - fluid moving in concentric layers, outer layer does not move at all (no slip condition due to contact with endothelium) and central layer moves fastest.
why is viscosity least in smallest vessels?
Fahraeus-Lindqvist Effect - Axial streaming (RBCs migrate to centre of lumen, plasma left near wall where friction is greatest) and Bolus Flow (RBC diameter takes up whole of capillary and sweeps along plasma).
why is viscosity lower at high flow rates (high shear rates)?
RBC aggregation into rouleaux (stacks) when shear low but when shear high the RBC flow freely.
give three methods of measuring blood flow
1) Tissue clearance - time for radioactive substance to decline after injected into small area of tissue
2) Plethysomography - pressure cuff occludes veins in limb and initial swelling in limb measured
3) Fick’s principle - constituents of blood measured before and after an organ and compared to normal increase/decrease in that organ
what is the normal hematocrit value in the blood?
45%
what are the three ways that blood flow is controlled locally?
1) Autoregulation - blood flow maintained through an organ across range of BPs due to myogenic response (muscle contraction narrows lumen). eg kidneys
2) Metabolic Hyperaemia - adjustment of perfusion to organ according to demand (changing metabolic rate). Greatest control of blood flow.
3) Human Alerting response
which blood vessels provide most resistance?
arterioles - blood flow control exert most at this level of circulation.
What is the lowest level of hierarchy of blood flow control mechanisms?
Intrinsic autoregulation - Myogenic response (vascular smooth muscle contracts in response to increased BP - stretch depolarises, Ca2+ influx, contraction
What is the intermediate level of the hierarchy of blood flow control?
Intrinsic Reactive Regulation
1) Metabolite control - products of respiration act as vasodilators (k+, CO2, adenosine)
2) Autacoid Control - autacoids (histamine, prostaglandins) released in damaged tissue - inflammation and dilation
3) Endothelial controls - endothelium excrete vasodilators like NO especially at high shear.
what is the highest level of hierarchy of blood flow control?
Extrinsic regulation (for the benefit of the whole organism)
1) vasomotor nerves - sympathetic vasoconstrictors (noradrenaline), sympathetic vasodilators (acetylcholine) and parasympathetic vasodilators (acetlycholine)
2) Hormones - adrenaline (vasodilation of fight or flight organs) and Renin/Angiotensin II (vasoconstriction, aldosterone release to increase water reabsorption in kidneys)
Describe the three models of stress
1) Stimulus model - external demands
2) Response model - response to stimulus (internal)
3) Transactional model - both stimulus and response perspectives
Describe General Adaptation Syndrome
Phase I - Alarm reaction mobilises resources
Phase II - Resistance, cope with stressors
Phase III - Exhaustion, reserves depleted
What is the body’s reaction to stress?
activation of sympathetic nervous system, adrenaline and noradrenaline release, release of corticosteriods
What acronym explains how to manage a patient suspected of an ACS (acute coronary syndrome)? What does it stand for?
MONA M - morphine (or diamorphine) O - oxygeb N - nitrates (GTN spray) A - anti-platelets (aspirin)
What are the MI-5 drugs?
Aspirin Clopidogrel ACE-inhibitor (ramipril) B-blocker (bisoprolol) Statin (simvastatin)
What is the mechanism of action of aspirin?
Irreversibly inhibits COX-1 and COX-2 enzymes. This inhibits the formation of thromboxane A2 -> inhibiting platelet aggregation
What are the side effects of aspirin?
GI irritation
GI haemorrhage
Bronchospasm
Name some contraindications for aspirin
Hypersensitivity
Active peptic ulcer
Haemophilia (and other bleeding disorders)
What is the mode of action of clopidogrel?
Irreversibly blocks P2Y12 components of adenosine receptors on platelet surface
Is clopidogrel usually used as a mono therapy or dual therapy?
Dual - may be prescribed as a monotherapy in patients that cannot tolerate aspirin.
Is used with aspirin as a dual therapy.
What are some side effects and contraindications for clopidogrel?
GI irritation
GI haemorrhage
Contraindications: active bleeding
Name some drugs that interact with clopidogrel to reduce its antiplatelet effect
Carbamazepine
Fluconazole
PPIs
What are prasugrel and ticagrelor?
Anti-platelet drugs with a similar mode of action to clopidogrel. They can both be used with aspirin. Both contraindicated with active bleeding and can cause GI haemorrhage
What is the mechanism of action of ramipril?
Inhibits angiotensin converting enzyme (ACE) and prevents the formation of angiotensin II - this prevents vasoconstriction and the formation of aldosterone
What are some side effects of ACE inhibitors such as ramipril?
Dry cough, hyperkalaemia, renal impairment, angioedema, hepatic impairment
What type of drugs do ACE inhibitors interact with?
Diuretics
What is the mechanism of action of beta blockers?
Reduces sympathetic drive, causing a reduction in HR and myocardial contractility.
What are some side effects of beta blockers?
Bronchospasm Bradycardia Cold extremities Sleep disturbance Fatigue Sexual dysfunction
What drugs could be given in patients unable to tolerate beta blockers?
Diltiazem or verapamil
How do statins work?
Inhibit HMG CoA reductase, which is an enzyme involved in cholesterol synthesis. Inhibition of HMG CoA reductase lowers LDL-c levels by slowing production of cholesterol in the liver and increasing the liver’s ability to remove LDL-c
What are some common side effects of statins?
Headache
Altered liver funcion
Myalgia
What do statins interact with?
Grapefruit juice!
Clarthromycin
Fluconazole
Fusidic acid
