Ischaemic Heart Disease Flashcards
1
Q
How is IHD now considered, compared to how it was previously taught?
A
More of a “spectrum” of disorders
2
Q
What are the three names used to describe the same disorder related to heart disease?
A
Ischaemic Heart Disease, Coronary Heart Disease, Coronary Artery Disease
3
Q
What are the two extremes of the spectrum of disorders now considered to be IHD?
A
Chronic Stable Angina to Unstable Angina/Acute Coronary Syndromes
4
Q
What are the acronyms for Myocardial Infarction with ST elevation and without ST elevation?
A
STEMI (STEACS)/NSTEMI (NSTEACS)
5
Q
What is the underlying cause of all conditions within the IHD spectrum?
A
Myocardial Ischaemia
6
Q
What are the main differences between the conditions within the myocardial ischaemia spectrum?
A
- The level or severity of the ischaemia
- Whether the ischaemia is temporary or permanent
- If permanent, the damage that occurs to the myocardium
- The risk of major CV events and/or death
7
Q
What does the heart act as in simple terms? What is the main function of the heart?
A
Muscular pump
Push blood around the body
8
Q
What does blood supply to tissues? What does blood ensure perfusion of? What does the heart require to function as a muscle?
A
O2 and nutrients
Essential organs and other tissues
A supply of O2 and nutrients (energy)
9
Q
What ensures that there is normally a balance between the supply and demand of O2 and nutrients? What occurs if insufficient O2 and nutrients reach the myocardium? What happens to the level of O2 in the tissues during ischaemia? What happens to the level of nutrients and energy during ischaemia?
A
Homeostatic mechanisms
The myocardium becomes ischaemic
It is low
They are low
10
Q
What happens to the level of waste products in the myocardium during ischaemia?
A
Increases
11
Q
What are the two main causes of an imbalance between O2/nutrient supply and demand? How does the body respond to increased O2 demand in a healthy person? What happens to the myocardium in IHD when demand outstrips the body’s ability to respond? What will happen if the ischaemia is not reversed?
A
Increased demand OR Decreased supply
Increase blood flow
It becomes ischaemic
Permanent damage will result
12
Q
What is hypoxia? What is hypoxemia? When might hypoxemia occur despite adequate blood flow?
A
Low oxygen levels in the tissues
A lack of oxygenation of the blood
Inadequate level of blood oxygenation
13
Q
What could cause an inadequate level of blood oxygenation? What is ischaemia? What causes ischaemia?
A
Problems with respiratory system or oxygen-carrying capacity
A deficiency of oxygen, nutrients due to deficient blood supply
Obstacles to blood flow
14
Q
What is the major cause of CHD?
A
Atherosclerosis
15
Q
What does atherosclerosis cause in the arteries?
A
Progressive narrowing of the arterial lumen
16
Q
What does the narrowing of arteries due to atherosclerosis predispose to?
A
Processes that can precipitate myocardial ischaemia
17
Q
What processes can atherosclerosis predispose to that can precipitate myocardial ischaemia?
A
- Thrombus formation
- Coronary vasospasm
- Endothelial cell dysfunction
18
Q
What are some less common causes of cardiac ischaemia?
A
- Abnormalities of blood O2 content
- Poor perfusion pressure through the coronary arteries
19
Q
What condition can cause abnormalities of blood O2 content? What conditions can cause poor perfusion pressure through the coronary arteries?
A
Respiratory failure
Hypotension, hypovolaemia
20
Q
What can be the cause when patients show signs of cardiac ischaemia but have no atherosclerosis?
A
Issues with the microcirculation
21
Q
What are the non-modifiable risk factors for atherosclerosis?
A
- Age (>45yrs men, >55yrs women)
- Gender (Male)
- Family Hx of premature CHD
22
Q
What constitutes a family history of premature CHD?
A
- MI or sudden cardiac death in male relative (First-degree relative at age <55 yrs)
- MI or sudden cardiac death in female relative (First-degree relative at age <65yrs)
23
Q
What are the non-Lipid risk factors for atherosclerosis?
A
- Hypertension
- Cigarette smoking
- Thrombogenic states
- Diabetes
- Obesity
- Physical inactivity
- Poor diet (atherogenic)
24
Q
What are the lipid risk factors for atherosclerosis?
A
Elevated circulating lipids
25
What is the target non-HDL level for primary prevention of CVD for patients with increased CV risk?
40% reduction in Non-HDL
26
What is the target non-HDL level for secondary prevention of CVD for patients with increased CV risk? What is the target LDL level for secondary prevention of CVD for patients with increased CV risk?
Non-HDL <2.6 mmol/L
LDL <2mmol/L
27
What are some emerging risk factors for atherosclerosis?
- Lipoprotein(a)
- Small LDL particles (pattern B)
- HDL subtypes
- Apolipoprotein B
- Homocysteine
- Fibrinogen
- High –sensitivity C-reactive protein
- Impaired fasting glucose
28
How are lipids transported through the bloodstream? What are the proteins that lipids combine with for transport called? What are lipid-protein molecules called?
In combination with specific proteins
Apoproteins
Lipoproteins
29
What are lipoproteins associated with? How many major types of lipoproteins are there with differing risk of atherosclerosis? Which lipoprotein is high in cholesterol and poses the highest risk for atherosclerosis? Which lipoprotein is high in triglycerides and increases the risk for atherosclerosis?
A greater risk of atherosclerosis
5
Low-density lipoprotein (LDL)
Very low density lipoprotein (VLDL)
30
How does HDL affect the risk of atherosclerosis?
Decreased risk of atherosclerosis
31
How does HDL decrease risk of atherosclerosis? What effect does nicotine have on the development of atherosclerosis?
Transports cholesterol from tissues back to liver
Atherogenic effects
32
What are the atherogenic effects of Nicotine?
1. Augments the conversion of LDL- Ox- LDL
2. Decreases HDL levels
3. Inappropriate stimulation of sympathetic activity
4. Displacement of O2 by CO in Haemoglobin - creates hypoxia
5. Enhanced platelet adhesiveness - Enhanced clot formation
6. Causes release of elastases - Increased risk of damage to walls of blood vessels
33
How does mechanical damage to vessels from hypertension contribute to atherosclerosis?
Helps to create a point of entry for LDL
34
Where does atherosclerosis often occur in blood vessels? How does diabetes contribute to atherosclerosis?
At branches or curves
Glycosylation of lipoproteins enhances cholesterol uptake
35
What other effect, besides glycosylation of lipoproteins, does diabetes have that contributes to atherosclerosis?
Increased platelet adhesiveness
36
What is the first step in atherosclerotic plaque formation? What initiates atherosclerotic plaque formation?
Chronic endothelial injury
Injury to the coronary artery endothelium
37
What are potential mechanisms that could cause endothelial dysfunction and initiate atherosclerotic plaque formation?
- Haemodynamic wall stress
- Nicotine and Toxins from cigarette smoke
- Hyperlipidaemia
- Circulating cytokines
38
What explains why atherosclerotic plaques often occur at arterial branch points?
Haemodynamic wall stress
39
What happens to the endothelium after injury in the formation of atherosclerotic plaque? What happens to LDL cholesterol after endothelial injury?
Becomes more permeable and recruits leukocytes
Leak through the endothelium into vessel wall
40
What modifies LDL cholesterol in the vessel wall? What happens to excess lipid and cell debris in the vessel wall?
They are oxidised (Ox-LDL)
Accumulates into a pool (lipid core)
41
What oxidizes LDL cholesterol in the vessel wall? What effect do oxidised lipids (Ox-LDL) have on endothelial and smooth muscle cells? What do oxidised lipids (Ox-LDL) stimulate?
Endothelial cells and macrophages
They are damaging
Recruitment of macrophages
42
What are lipid-filled macrophages called?
Foam cells
43
What do macrophages and foam cells release?
Inflammatory mediators and growth factors
44
What does the release of inflammatory mediators and growth factors by macrophages and foam cells stimulate?
Smooth muscle proliferation
45
What characterizes plaques with large lipid cores? How do atherosclerotic plaques affect the lumen of the blood vessel over time?
They are fragile and prone to rupture
Progressively occlude the lumen
46
What does rupture of the plaque lead to?
Exposure of subendothelial proteins and collagen
47
What does exposure of subendothelial proteins and collagen lead to?
Platelet aggregation and thrombus formation
48
When does significant reduction in blood flow typically occur due to plaque buildup? Where can clinically significant atherosclerotic plaque be located?
When plaque occupies 75% or more of the lumen
Anywhere within the 3 major coronary arteries
49
What is it called when all 3 coronary arteries are affected by atherosclerotic plaque?
"Triple vessel disease"
50
What three arteries are affected in "triple vessel disease"? What is a poor predictor of the severity of the resulting ischaemia?
Right, left anterior descending, left circumflex coronary arteries
The extent and severity of atherosclerotic diseases
51
What is a sign of stable plaques? What may unstable plaques lead to?
Usually asymptomatic or associated with exercise-induced angina
Thrombus formation or total occlusion
52
What are factors identified as risk factors for increased plaque instability?
- Active inflammation in the plaque
- A large lipid core with a thin cap
- Endothelial denudation (erosion) and platelet adhesion
- Fissured or rupture cap
- Severe stenosis predisposing high sheer stress
53
What occurs when the O2 supply fails to meet the metabolic demand of cardiac cells? Why do myocardial cells require a continuous supply of O2? Why is a steady flow of O2 important for myocardial cells?
Ischaemia of cardiac cells
For aerobic synthesis of ATP
Myocardial cells cannot slow their activity
54
What are the critical factors that upset the balance between myocardial O2 supply and demand and can cause ischaemia?
1. Rate of coronary perfusion (reduced)
2. Myocardial workload (increased)
55
What can impair coronary perfusion?
1. Large, stable atherosclerotic plaque
2. Acute platelet aggregation and thrombosis
3. Vasospasm
4. Failure of autoregulation by the microcirculation
5. Poor perfusion pressure
56
What factors can increase myocardial workload?
1. Heart rate
2. Preload
3. Afterload
4. Contractility
57
When does intermittent ischaemia occur due to advanced fibrous plaque?
When 75% or more of the lumen is occluded
58
How does the heart compensate for plaque development?
Develops alternative pathways
59
What are the alternative pathways the heart develops to maintain myocardial blood supply called? What results in acute myocardial ischaemia?
Collateral blood supply
Sudden obstruction of coronary blood flow
60
When do symptoms of chronic stable angina pectoris develop?
When O2 demand is suddenly elevated
61
What does plaque rupture lead to? What is ACS usually associated with? What forms on the ruptured plaque?
Exposure of collagen fibres and endothelial tissues
Rupture of a vulnerable atherosclerotic plaque
Platelets adhere which leads to clot formation
62
What risk do smokers and patients with hyperlipidaemias have?
Enhanced risk of clot formation
63
What can platelets adhering to the ruptured plaque stimulate?
Clotting cascade
64
What blocks the blood vessel in ACS?
A platelet-fibrin clot
65
How can collateral blood supply affect the development of symptoms in cases of nearly total occlusion?
It can maintain blood flow
66
Why might someone not develop symptoms of angina until physical activity? What symptoms does the described lack of blood flow lead to?
O2 demand is suddenly elevated
Chronic stable angina pectoris
67
What is acute coronary syndrome (ACS)? What is ACS usually associated with?
Rupture of a vulnerable plaque
Sudden obstruction of coronary blood flow
68
What happens when a vulnerable atherosclerotic plaque ruptures? What adheres to the ruptured plaque, leading to clot formation?
Collagen fibres and endothelial tissues exposed
Platelets
69
High fibrinogen levels and enhanced platelet adhesiveness increase risk of what? What can the platelet plug stimulate?
Clot formation
Clotting cascade, release of fibrin
70
What does the formation of a platelet-fibrin clot do?
Blocks the blood vessel
71
What term is used to describe the group of syndromes caused by myocardial ischemia? What is myocardial ischaemia mainly due to?
Ischaemic Heart Disease
Decrease in coronary blood flow
72
What are the different types of Ischaemic Heart Disease?
Chronic stable angina, variant angina, silent ischaemia, ACS
73
What are the primary causes of decreased coronary blood flow?
Fixed obstruction, vasoconstriction, thrombus, aggregation
74
What is angina caused by? What are common features of angina?
Reversible myocardial ischaemia
Central chest pain and SOB
75
What is myocardial infarction caused by? What can myocardial ischaemia occur secondary to?
Myocardial ischaemia causing necrosis
Increased O2 demand or decreased supply
76
What is another name for chronic stable angina? What is the prominent disorder restricting coronary blood flow in chronic stable angina? In chronic stable angina, when is coronary blood flow insufficient? What typically triggers the onset of symptoms (chest pain) in chronic stable angina?
Angina pectoris or effort angina
Atherosclerosis
When O2 demand increased
Activities increasing myocardial O2 demand
77
What relieves the symptoms of chronic stable angina? What are the classic symptoms of chronic stable angina? What does "stable" suggest in chronic stable angina?
Rest
Retrosternal heaviness, pressure or pain
Attacks' frequency, intensity, duration stable
78
When do patients with chronic stable angina rarely experience pain? What is unstable angina characterized by? What should chronic stable angina patients do regarding their symptoms?
At rest or night
Sudden worsening of angina symptoms
Monitor and report any changes
79
What is the average number of angina attacks per week in chronic stable angina? What do many patients with chronic stable angina do to avoid attacks?
About 2 per week
Curtail activities
80
How long does it typically take for discomfort to be relieved by rest in chronic stable angina? How can discomfort be relieved more rapidly than by rest?
Within 1-5 minutes
With SL GTN
81
What are patients with chronic stable angina at risk of developing? What is unstable angina sometimes called?
Acute coronary syndrome (ACS)
Intermediate coronary syndrome
82
What are the three subgroups of unstable angina?
Initial frequent attacks, worsening stable angina, recurring angina at rest
83
What is a problem with patients who experience increases in the frequency/intensity of previously stable angina?
Reduced response to sublingual nitrates
84
What is often the cause of unstable angina?
Disruption of atherosclerotic plaque
85
What does the disruption of an atherosclerotic plaque cause? What is the result of partial occlusion of coronary arteries in unstable angina?
Aggregation, thrombus formation, vasoconstriction
Blood flow not meeting O2 demand causing pain at rest or nocturnal pain
86
What is Prinzmetal angina considered part of? What is Prinzmetal angina due to? What does Prinzmetal angina result in? What time of day do attacks of Prinzmetal angina often occur?
Spectrum of unstable angina/ACS
Coronary vasospasm
Spontaneous attacks of angina at rest
Night or early morning
87
What is the risk of progression to myocardial infarction in Prinzmetal angina? In whom is Prinzmetal angina more common?
High
Younger women
88
What do patients with silent ischemia experience?
When is silent ischemia often detected? How common are silent ischemic episodes compared to symptomatic ones?
No pain
On ECG when checking for other problems
More common in all IHD patients
89
What are the three main treatment goals for the management of chronic stable angina?
1. Limit the number, severity and sequelae of angina attacks, improve quality of life
2. Protect against future ischaemic syndromes
3. Reduce the risk of atherosclerotic progression
90
What are the symptomatic treatment aims for angina?
1. Terminate individual angina attacks
2. Prevent immediate onset of attacks before activity
3. Long term prophylaxis to prevent or reduce angina attacks
4. Increase exercise capacity and reduce acute therapy administration
5. Identify and treat cardiovascular risk factors
6. Reduce cardiovascular morbidity and mortality
91
What are the pharmacological treatment aims for angina?
1. Reduce preload and augment coronary circulation
2. Reduce inotropic and chronotropic stress
3. Decrease oxygen demand of myocardium
4. Stop active thrombus formation
92
What drug groups are commonly used in the treatment of chronic stable angina?
- Organic nitrates
- Beta Blockers
- Calcium Channel Blockers
- Potassium Channel Activators
- Antiplatelet drugs
- Ivabradine
- Ranolazine
- Perhexilene
93
How do nitrates work? What effect do nitrates have on vascular beds?
Converted to nitric acid which increases cGMP causing vasodilation
Potent vasodilators
94
Which is usually greater in nitrates, venodilation or arteriolar dilation?
What effect do nitrates have on vessels narrowed by atherosclerosis? What effect do nitrates have on large epicardial vessels?
Venodilation
Dilate
Dilate, greater perfusion of the heart
95
How do nitrates reduce workload and preload? What effect do nitrates have on afterload at high doses?
Dilate venous system, blood pools, less blood returns
Reduce afterload
96
Why do nitrates differ in their uses?
Differences in pharmacokinetics
97
How is GTN used? What is the Tpeak and duration of GTN via the sublingual route?
Sublingually for acute attacks or transdermally long-term
Tpeak=4mins, duration=20-30mins
98
What is the Tpeak and T1/2 of ISDN (Isosorbide Dinitrate)? How can ISDN be used?
Tpeak=6mins T1/2 =45mins
S/L for acute treatment and orally long-term
99
How is ISMN (Isosorbide Mononitrate) used? Why is nitrate free period needed for immediate release ISMN?
2-3 times daily (immediate release) or once daily (SR)
To avoid nitrate tolerance
100
What are many nitrate adverse effects usually due to? What is the most common adverse effect when starting nitrate treatment? What causes dizziness as an adverse effect of nitrates? Why does reflex tachycardia occur?
Vasodilation in other tissues
Headache
Vasodilation causes drop in BP
Due to BP drop
101
What is an important consideration with nitrate prophylaxis?
Nitrate tolerance
102
What is believed to cause nitrate tolerance? What is the best treatment for nitrate tolerance?
Impaired conversion of nitrates to NO
Prevention with a nitrate free period
103
Should a patient take GTN during their nitrate-free period if they experience chest pain?
Yes
104
What is the relationship between coronary blood flow and myocardial oxygen demand in stable angina? Why is it important for patients with chronic stable angina (CSA) to monitor and report changes in their symptoms?
Sufficient at rest, insufficient during exertion
Detect progression to unstable angina
105
Why does once daily dosing of Imdur (ISMN) help prevent nitrate tolerance? How can nitrate tolerance be avoided with sustained-release Isosorbide Mononitrate (SR ISMN)?
Allows for a nitrate-free period
Dosing SR ISMN
106
What is GTN used for when administered sublingually? How can nitrate tolerance be avoided with GTN patches?
To treat acute angina attacks
Removing GTN patches at night
107
For a patient with chronic stable angina having a nitrate-free period, are they at a greater risk of an angina attack during this period?
Probably notm nocturnal attack risk are low
108
For a patient with unstable angina, what additional medication should be used for prophylaxis, along with a nitrate-free period?
Beta blocker
109
If a patient with CSA taking Imdur and GTN experiences chest pain at 9pm during their nitrate-free period, should they take GTN?
Yes, they should take GTN
110
What route of administration is used for Glyceryl Trinitrate (GTN) to treat an acute angina attack? What are the two forms of Glyceryl Trinitrate (GTN) available for this type of administration?
Sublingual route
Tablets and spray
111
Why should a patient sit down when taking sublingual GTN? What should a patient experiencing chest pain do while a GTN sublingual tablet is dissolving?
Resting and to avoid fainting due to BP drop
Not eat or drink
112
After taking the first dose of GTN, how long should a patient wait to see if the pain subsides? If chest pain persists after a second dose of sublingual GTN, what action should the patient take?
5 mins
Take one more dose and dial 999 and go to the hospital
113
If a patient knows an activity will provoke angina, when should they use GTN?
Immediately before the activity
114
Where should GTN tablets be stored to maintain their effectiveness? What sensation under the tongue is associated with GTN tablet effectiveness? How often should GTN sublingual tablets be replaced after opening? Why does the spray formulation of GTN have fewer storage issues than tablets?
Original glass container in a cool place
A tingle
Every 8 weeks
GTN spray is very volatile
115
What are common side effects of organic nitrates like GTN?
Dizziness and headaches
116
For a patient experiencing headaches from GTN, what initial dose adjustment might be recommended? What can patients do with tablet remains of GTN once chest pain subsides?
Use half a tablet initially
Spit out any remains
117
Where on the body should transdermal GTN patches be applied? Why should lotions, creams, or powders be avoided before applying a GTN patch? What can be used to secure GTN patches in cases of excessive sweating? Why are GTN patches typically removed at bedtime?
Clean dry hairless area
Prevent patch sticking
Tape
Allow nitrate-free period
118
What is meant by "carriage of patch onto others" in relation to GTN patches? When applying a new GTN patch, how should the application site be varied? How should used GTN patches be disposed of?
Patch transfers to others
Apply to different area
Carefully out of child's reach
119
How should Isosorbide Mononitrate SR products be taken? Why should Sildenafil (Viagra) or similar products be avoided if nitrates have been taken in the last 24 hours?
Orally, once daily, swallow whole
Risk of sudden death due to dangerous drop in BD
120
What effect do beta blockers have on angina attacks? What is the mechanism of action of beta blockers?
Reduce severity and frequency
Block catecholamines on Beta-adrenoceptors
121
Name four cardiac conditions for which beta blockers are widely used?
IHD, hypertension, post-MI, antiarrythmic
122
If α1 adrenoceptors are blocked, what effect will occur? What effect will blocking β1 adrenoceptors have? What effect will blocking β2 adrenoceptors have?
Antihypertensive effects
Opposite of β1 agonists
Opposite of β2 agonists
123
What is the mechanism of action of Beta Blockers in Chronic Stable Angina (CSA)? How do beta blockers lower oxygen consumption?
Reduce left ventricular work
Reduce myocardial contractility and arterial BP
124
How do beta blockers lower heart rate? Drug choice for beta blockers depends on what 4 factors?
Reduced cardiac work and O2 demand
Cardioselectivity, ISA, metabolism, solubility
125
Where do β1 receptors predominate? Where do β2 receptors predominate? What is the ideal selectivity for beta blockers? Although some beta blockers are cardioSELECTIVE, are any cardioSPECIFIC?
Cardiac tissue
Lungs and peripheral vasculature
Block β1, not β2
No
126
At high doses, can cardioselective beta blockers cause side effects? What are beta blockers with Intrinsic Sympathomimetic Activity (ISA)?
Yes, can block β2 receptors
Partial agonists
127
In theory, what side effects should be reduced with ISA (Intrinsic Sympathomimetic Activity) beta blockers? Has the clinical significance of ISA been proven?
Bradycardia and cold extremities
Not proved
128
Which beta blockers may be preferred in patients with hepatic impairment? Which beta blockers are less likely to cross the BBB and cause CNS side effects?
Water-soluble, renally eliminated (atenolol, nadolol)
Water-soluble, renally eliminated (atenolol, nadolol)
129
What effect does Alpha1 blockade give beta blockers?
Vasodilating properties
130
How many times a day should Atenolol be taken? What is the main route of elimination for Atenolol? What receptors are blocked by Bisoprolol? What is the main route of elimination for Bisoprolol? What receptors are blocked by Carvedilol? What is the main route of elimination for Carvedilol?
Once
Renally
β1
Hepatically and renally
α1, β1, β2
Hepatically
131
What is the ISA (Intrinsic Sympathomimetic Activity) of Oxprenolol?
Positive
132
List some adverse effects of Beta Blockers
How do beta blockers affect diabetes? Can beta blockers be used in the management of heart failure?
Dizziness, bradycardia, bronchospasm
Enhance hypoglycaemic effects & mask signs
Yes if prescribed appropriately
133
How should beta blockers be discontinued? In what types of patients should Beta blockers be avoided?
Reduce doses over 2-6 weeks
Asthma, diabetes
134
How do Calcium Channel Blockers work? What are the mechanisms of action of Calcium Channel Blockers in CSA? What are the two main groups of Calcium Channel Blockers?
Block Ca2+ ions into cells
Reduced O2 demand, increased O2 supply
Dihydropyridines and Non-Dihydropyridines
135
Name some Dihydropyridines Calcium Channel Blockers
Name some Non-Dihydropyridines Calcium Channel Blockers
Amlodipine, Felodipine, Lercandipine, Nifedipine
Diltiazem, Verapamil
136
Where do Dihydropyridines primarily act? What can potent and rapid vasodilatation in short acting Dihydropyridines drugs cause? What is Nimodipine used for?
Vascular smooth muscle
Reflex increase in heart rate
Prevent cerebral ischaemic damage
137
Where do Non-dihydropyridines block influx of Ca ions? What can Non-dihydropyridines cause? Which Non-dihydropyridine has greater cardiac effects?
Cardiac and vascular tissue
Bradycardia
Verapamil
138
What is the acronym for dihydropyridine calcium channel blockers? How do dihydropyridines primarily act on vascular smooth muscle?
ANFL group
With minimal effect on contractility and sinus AV node conduction
139
What can short-acting dihydropyridines cause due to rapid vasodilation? Which dihydropyridine may prevent cerebral ischemic damage following subarachnoid hemorrhage?
A reflex increase in heart rate and myocardial O2 demand
Nimodipine
140
How do non-dihydropyridines (Verapamil, Diltiazem) block calcium influx? Why are non-dihydropyridines not usually described as being cardioselective? What effects can Verapamil and Diltiazem have on heart rate?
In both cardiac and vascular tissue
They act on both cardiac and vascular tissue
Cause bradycardia or limit exercise-induced increases in HR
141
How does Diltiazem act on cardiac and vascular smooth muscle compared to Verapamil? What are the cardiac effects of Verapamil?
Less effect on cardiac cells than verapamil
Reduces contractility, HR and conduction with less effect on vascular smooth muscle
142
What determines the adverse effects of calcium channel blockers (CCBs)? Which calcium channel blockers (CCBs) act more on vasculature?
Specificity of action on vasculature versus heart
Lercandipine, Amlodipine, Nifedipine and Felodipine (LA
143
What conduction-related side effects can Diltiazem and Verapamil (D&V) cause? What beverage should patients use caution with while taking Verapamil and Diltiazem?
Bradycardia and heart block
Grapefruit juice
144
What are common adverse effects of all calcium channel blockers (CCBs)?
Headaches and oedema
145
What cardiovascular effect is more common with LANF calcium channel blockers?
Reflex tachycardia due to reduced BP
146
What is the mechanism of action of Nicorandil? What additional property does Nicorandil have due to its nitrate moiety?
ATP-dependent potassium channel activator, found in cardiac, smooth muscle and skeletal muscle
Arterial and venous vasodilation
147
What effects does Nicorandil have on myocardial oxygen balance? What is the effect of Nicorandil during acute ischemic episodes? Does Nicorandil exhibit nitrate-like tolerance?
Improves myocardial oxygen balance and decreases angina
May be cardioprotective
No evidence on nitrate-like tolerance
148
Is Nicorandil considered a first-line therapy for angina? What are common adverse effects of Nicorandil? What are uncommon adverse effects of Nicorandil?
Not 1st line therapy
Headache, dizziness, lethargy, myalgia
Painful oral and perianal ulcers, fistulae
149
What is the effect of Ivabradine on anginal symptoms and exercise capacity? Is the effect of Ivabradine on cardiovascular outcomes and mortality clear? When is Ivabradine mainly used?
Improves symptoms and exercise capacity
Effect on cardiovascular outcomes and mortality is unclear
If patient cannot tolerate other antianginal agents
150
What is the mode of action of Ivabradine? How does Ivabradine lower heart rate at the SA node?
Selective sinus node inhibitor
Without negative inotropic effects
151
What current does Ivabradine inhibit in the SA node? How much does Ivabradine reduce heart rate? How does Ivabradine reduce cardiac workload and myocardial O2 demand?
Current regulating the interval between depolarisations
Reduces heart rate by ~10bpm
By reducing heart rate
152
What is an indication for Ivabradine use? What are contraindications for Ivabradine use?
1. CSA with normal sinus rhythm
2. HR <60bpm, artificial pacemaker, sick sinus syndrome, 3rd Degree Heart block, NYHA class III & IV heart failure and Hepatic impairment
153
What are side effects of Ivabradine? What are luminous effects associated with Ivabradine? How are luminous effects from Ivabradine usually resolved? What substances should be used with caution with Ivabradine?
Luminous effects, blurred vision, bradycardia, AV block, ventricular extrasystoles
Transient areas of enhanced brightness in the visual field
Spontaneously resolve
Grapefruit Juice and CYP3A4 inhibitors/inducers
154
How is Ranolazine's mode of action best described? What effects does Ranolazine have on the myocardium?
Not well understood
Improves relaxation, reduces LV stiffness, improves cardiac reperfusion
155
What current does Ranolazine inhibit in cardiac cells? What ion concentrations are reduced by Ranolazine's inhibition of the late inward Na+ current?
Late inward Na+ current
Cellular Na+ and Ca2+ ions
156
Is Perhexiline commonly used in the UK? When is Perhexiline used in countries where it is available? How is Perhexiline typically tolerated if monitored correctly?
Not used in UK
Refractory angina after revascularisation
Well tolerated w/o S/Es if monitored
157
What is the typical dosing regimen for Perhexiline? What Perhexiline levels should be maintained? What dosage do slow metabolisers of Perhexiline typically require per week? What Perhexiline levels indicate hepatotoxicity and peripheral neuropathy?
200mg BD for 3 days, then 200mg daily
0.15-0.6mg/L
50-100mg per week
Levels >1.2mg/L
158
What percentage of patients experience side effects during the loading stage of Perhexiline? How are the side effects during the loading stage of Perhexiline usually managed? Is long term toxicity common with Perhexiline if levels are monitored?
60%
Dose reduction
Long term toxicity rare if levels monitored
159
What is the typical low dose range for Aspirin in secondary prevention? Is the benefit of Aspirin for primary prevention well-established? What is the recognized action of Aspirin in secondary prevention for unstable angina?
75-150mg daily in UK
Subject to debate
Reducing mortality
160
What cardiovascular events does Aspirin reduce the incidence of? When should Aspirin be considered for patients with angina?
MI and death
Benefits outweigh the risks
161
What are Clopidogrel & Ticlopidine? What did the CAPRIE study show about Clopidogrel? How do Clopidogrel & Ticlopidine compare to Aspirin in terms of GI effects, rash, and diarrhoea?
Thienopyridines
Superior efficacy in preventing ischemic stroke, MI and vascular death
Less GI effects, more rash & diarrhoea
162
What hematological side effects can occur with Clopidogrel & Ticlopidine? When are Clopidogrel & Ticlopidine commonly used?
Neutropenia and thrombocytopenia
After revascularisation or aspirin allergy
163
What class of drugs are statins? What risk reduction have statins shown for all-cause mortality? What risk reduction have statins shown for cardiovascular mortality?
HMG Co-A Reductase inhibitors
Relative risk reduction of 0.79
Relative risk reduction of 0.75
164
Should statins be offered to all patients with stable angina? What are the target lipid levels when treating with statins?
Yes, cost effective intervention
TC<4mmol/L, LDL<2mmol/L, HDL>1mmol/L
165
What is the aim of acute therapy for angina attacks? What should a patient do during an acute angina attack?
Relieve pain ASAP
Stop activity, sit down, and take SL GTN
166
What is the typical dose of SL GTN for acute angina? How often can SL GTN be repeated during an acute angina attack? What are alternative formulations to SL GTN? Should GTN be given to all patients with angina?
300-600microgram PRN
Every 5 mins, max 3 doses in 15 mins
SL ISDN or GTN spray
Yes
167
When should nitrates be avoided in angina patients?
If patient has used Sildenafil in last 24 hours
168
What is the aim of continuing therapy (prophylaxis) for angina? What is the typical first-line therapy for angina? What are typical beta blockers used in first-line angina therapy? What additional medication should be used before activity likely to provoke angina attacks?
Reduce angina attacks, improve exercise capacity, slow atherosclerosis
Aspirin PLUS a beta blocker
Atenolol OR metoprolol
S/L GTN
169
What medication should be used to treat any acute angina attacks?
S/L GTN
170
What medication is used if a patient is allergic to Aspirin?
Clopidogrel
171
What type of Calcium Channel Blocker (CCB) is substituted for a beta blocker if it is contraindicated? What other medications can be used in place of a beta blocker if it is contraindicated?
Non-dyhydropridine
Long acting nitrate and/or nicorandil
172
If a CCB is used first-line for angina, what type of CCB should be used?
Non-dihydropyridine is used
173
What is done if the beta blocker alone does not prevent angina attacks in second line therapy?
ADD a dihydropyridine Ca channel blocker and/or long acting nitrate
174
Why is a dihydropyridine Ca Channel blocker used in second line therapy for angina in addition to beta blockers? Why should a non-dihydropyridine Ca Channel blocker should NOT be added to the beta blocker?
Beta blocker will reduce tachycardia caused by the CCB
Risk of additive bradycardia
175
Which of the non-dihydropyridine Ca Channel blockers is generally contraindicated when taking beta blockers?
Verapamil
176
If a non-dihydropyidine Ca Channel blocker was used as the 1st line agent, what should we NOT add as the second line agent for angina?
A dihydropyridine Ca channel blocker
177
What additional treatment options are considered in third line therapy for angina?
Additional agents and/or revascularisation
178
What defines refractory angina?
Angina not responding to standard drug therapy
179
What is the typical daily dosage range of Aspirin?
75-325mg once daily
180
What two factors, alone or in combination, is Myocardial Ischaemia secondary to? What usually causes Myocardial infarction? How quickly does necrosis of myocardial tissue begin after occlusion? How long after occlusion will permanent necrosis occur if not resolved?
Increased myocardial oxygen demand or decreased supply
Permanent occlusion of a coronary blood vessel
Within 30 mins
6-12 hours
181
What distinction was management of unstable angina and ACS based on in the past?
Q-wave and Non-Q-wave infarction
182
What ECG characteristic is seen immediately in Q-wave infarction? What eventually develops on ECG after a Q-wave infarction? What usually causes Q-wave infarction?
ST segment elevation
Q waves
Total occlusion of coronary artery
183
What ECG characteristic is seen at admission with Non-Q-wave infarction? How was Non-Q-wave infarction distinguished from unstable angina?
No ST segment elevation
Persistence of ECG changes and rise in serum markers (troponin T and I, CK-MB)
184
What is Non-Q-wave infarction commonly associated with? What is infarction described in terms of?
Partial occlusion of the blood vessel
Presence or absence of ST segment elevation
185
What is the purpose of the new terminology in describing myocardial infarction?
To accurately describe the syndrome at presentation
186
What new group of patients does the new terminology ((non or) ST segment elevation) describe?
Elevated serum cardiac troponin levels without elevated CK
187
What is Q-wave myocardial infarction now referred to as? What is Non-Q-wave myocardial infarction referred to as now?
STEMI or STEACS
NSTEMI or NSTEACS
188
What is the relationship between unstable angina, minor myocardial damage, and non-STEMI?
They are considered a continuum
189
What are prognosis and treatment closely related to in the continuum of unstable angina, minor myocardial damage, and non-STEMI?
Serum troponin levels
190
What is required for diagnosing MI? What is the final definitive diagnosis of MI based on?
Clinical evaluation, ECG interpretation, and risk assessment
Markers of myocardial necrosis becoming evident
191
What are some presentations of ACS? What are other presentations of ACS? In whom is atypical pain presentation of ACS more common?
Chest pain at rest or recurrent discomfort
Back, neck, arm or epigastric pain, chest tightness, dyspnoea, diaphoresis
Women, diabetics and elderly
192
What is the diagnostic pathway for ACS?
1. Clinical presentation and initial ECG lead to a working diagnosis (STEMI or NSTEMI/NSTEACS).
2. Time and evolution of ECG and biomarkers lead to final diagnosis (STEMI, NSTEMI/NSTEACS, or Unstable Angina).
3. Myonecrosis confirmed or not confirmed.
4. Prognosis correlates with serum troponin levels.
193
What are Cardiac troponin I and T? When is Troponin released into the blood stream? What do high sensitivity Troponin assays allow?
Specific cardiac structural proteins
When there is myocyte injury
Precise measurement at very low concentrations
194
When does an elevated hs Troponin T indicate an MI? What is hs troponin used for?
If the clinical presentation supports the diagnosis
Diagnosis, risk stratification, and treatment guidelines
195
When should Cardiac troponins be measured? What can cardiac troponins be used for? What treatment responses can troponins predict?
6-8 hours after chest pain onset
To tailor therapy
LMWH, Tirofiban, and Abciximab
196
What kind of molecule is Creatinine kinase? When is Creatinine kinase elevated?
Enzyme
When muscle fibres are damaged
197
What are the acute management steps for acute chest pain?
1. Seek medical help (call ambulance).
2. Aspirin 300mg (chew and swallow) unless contraindicated.
3. Oxygen.
4. GTN and IV morphine if required.
198
What are the initial investigations for acute chest pain?
1. Immediate ECG
2. Doctor to see patient within 10 minutes
3. Commence oxygen
4. Pain relief
5. Blood tests for biomarkers
6. Aspirin 300mg unless already given
199
What are the aims of STEMI treatment?
- Relieve pain
- Achieve coronary reperfusion and minimize infarct size
- Prevent and treat heart failure, shock, or other complications
- Prevent and treat cardiac arrest
- Allay unnecessary anxiety
200
What are the ECG features of STEMI?
ST-segment elevation or new left bundle branch block
201
How much ST-segment elevation in contiguous limb leads indicates STEMI? How much ST-segment elevation in contiguous chest leads indicates STEMI?
>1mm
>2mm
202
When should patients with STEMI receive reperfusion therapy? What is the treatment of choice for STEMI?
Within 12 hours of symptom onset
Reperfusion (fibrinolysis or PCI (percutaneous coronary intervention), PCI preferred)
203
What type of drugs are Alteplase and Tenecteplace?
Clot dissolving drugs
204
In reperfusion therapy, when is fibrinolysis carried out?
When PCI is not available or delayed
205
What factors influence the choice of reperfusion therapy?
- Time delay to PCI
- Time from symptom onset to medical contact
- Time to hospital fibrinolysis
- Contraindications to fibrinolytic therapy
- Location and size of infarct
- Presence of cardiogenic shock
- Other special circumstances
206
What are the absolute contraindications to thrombolysis?
- Active bleeding (excluding menses)
- Significant closed head or facial trauma within 3 months
- Suspected aortic dissection
- Prior intracranial haemorrhage
- Ischaemic stroke within 3 months
- Known structural cerebral vascular lesion or malignant intracranial neoplasm
207
What are the relative contraindications to thrombolysis?
- Concurrent anticoagulants
- Non-compressible vascular punctures
- Recent major surgery (<3 weeks)
- Traumatic or prolonged (>10 minutes) CPR
- Recent internal bleeding (within 1 month)
- Active peptic ulcer
- History of chronic, severe, poorly controlled hypertension or severe uncontrolled hypertension on presentation
- Ischaemic stroke (>3 months), dementia, or intracranial abnormality
- Pregnancy
208
What are the options for Fibrinolysis/Thrombolytic therapy? What are the side effects of thrombolytics?
Streptokinase, Alteplase, Tenecteplase
- Bleeding (major haemorrhage)
- Allergic reactions (common with streptokinase)
209
Why should Streptokinase not be given to patients with previous exposure >5days before? What is advantageous about alteplase and tenecteplase? When is Alteplase superior to streptokinase?
Risk of antibody presence
Better reduction in mortality compared to streptokinase
Patients <75
210
How is Alteplase administered? Why is Tenecteplase considered convenient? What is an advantage of Tenecteplase over alteplase?
Bolus followed by infusion
Given as boluses
Lower bleeding rates
211
How are complications of STEMI managed?
- Complications are managed as they occur
- Common problems include:
- Persistent or recurrent pain
- Left ventricular failure
- Cardiogenic shock
- Arrhythmias
212
How does management of NSTEACS differ from STEMI?
Less defined
213
What is the initial evaluation for patients with chest pain without ST elevation? What guides therapy if indications for perfusion therapy are absent?
Assessment for indications of perfusion therapy
Risk stratification
214
What is the first objective of evaluating NSTEACS patients? What percentage of NSTEACS cases may have normal or minor ECG changes? What tests should be performed on all NSTEACS patients?
Determine whether ACS is the actual cause of presentation
Up to 50%
High sensitivity troponin tests
215
What investigations aid the evaluation of NSTEACS? What is the second objective of evaluating NSTEACS patients? How are NSTEACS patients effectively evaluated and treated?
Clinical history, examination, ECG, chest X-ray
Determine risk of short-term adverse outcomes
Based on their 6-month risk of death or MI
216
What is the predicted 6-month mortality risk in high-risk or Intermediate-risk NSTEACS patients? What is the predicted 6-month mortality risk in low-risk NSTEACS patients?
>3%
<3%
217
What scoring system is used to assess mortality risk in NSTEACS patients? What does the GRACE scoring system assess?
GRACE
6-month mortality or risk of CV event
