27. SIDH (stable ischaemic heart disease) and Angina therapy Flashcards
1
Q
What are 2 main types of ischaemic heart disease?
A
- Acute Coronary Syndrome
2. Chronic or Stable Ischaemia
2
Q
What are 2 main acute coronary syndromes?
A
- Myocardial infarction (STEMI or NSTEMI)
2. Unstable angina pectoris
3
Q
What are 2 main chronic or stable ischaemia conditions?
A
- angina pectoris (stable)
2. silent ischaemia
4
Q
What are main risk factors for ischaemic heart disease? (6)
A
- hypertension
- smoking
- hyperlipidaemia
- hyperglycaemia
- male
- post-menopasusal females
5
Q
What is the difference between stable and unstable angina?
A
- Stable angina is much more chronic, mainly on exertion or after doing a particular activity, much more controlled
- Unstable angina often occurs unexpectedly, worsening of symptoms occur, becoming more frequent and less exertion required (sometimes at rest), should be immediately treated as it’s emergency
6
Q
What is the purpose of drug treatment for stable ischaemic heart disease? (5)
A
- to relieve symptoms
- to halt the disease process
- regression of the disease process
- to prevent MI
- to prevent death
7
Q
What is hyperlipidaemia?
A
- disease of MUSCULAR arteries (not veins)
- mainly disease of coronary and cerebral vessels
- progressive deposition of cholesterol esters
8
Q
What does hyperlipidaemia present itself at the start as?
A
as atherosclerosis
9
Q
What does:
- ischaemic heart disease
- cerebrovascular disease
cause which can cause death?
A
-ischaemic heart disease causes MI
- cerebrovascular disease causes stroke
(which can both be fatal)
10
Q
What are the 2 main stages of plaque formation in atherosclerosis and when do they appear?
A
- lesions appearing as fatty streaks (aged approx. 20 years)
- fibrous plaque (more advanced stage of disease)
11
Q
What are the features of fatty streak lesions? (1)
A
- subendothelial accumulation of large foam cells which are derived from macrophages and SM cells filled with lipid
12
Q
What are the features of fibrous plaques?(4)
A
- more advanced and main cause of disease
- develop from fatty streaks
- projects into arterial lumen
- cause reduction in blood flow
13
Q
In which layers of the artery do most changes occur which lead to plaque deposition?
A
in the intimal layer
14
Q
Accumulation of what cells occurs in the intimal layer of arteries that lead to plaque formation? (4)
A
accumulation of monocytes, lymphocytes, foam cells and connective tissue
15
Q
What is the origin of most foam cells?
A
most are of smooth muscle origin
16
Q
What are 2 “part” of an atherosclerotic plaque?
A
- necrotic core
2. fibrous cap
17
Q
What results in stable ischaemic heart disease?
A
Arises as a result of MISMATCH between myocardial blood/ oxygen supply and demand
18
Q
What induces and stimulates attacks of angina (chest pain) in stable ischaemic heart disease?
A
- Any stress or exertion which increases cardiac work and myocardial oxygen demand
- Any activity that increases heart rate, stroke volume and blood pressure
19
Q
What is the relationship between O2 supply and O2 demand and myocardial ischaemia?
A
decrease ratio of O2 supply: O2 demand leads to myocardial ischaemia
20
Q
What can cause demand ischaemia?
A
-ischaemia during stress (physical or emotional)
21
Q
What can cause supply ischaemia?
A
ischaemia at REST
22
Q
What are the determinants of demand ischaemia? (4)
A
- heart rate
- systolic BP
- myocardial wall stress
- myocardial contractility
23
Q
What are the determinants of supply ischaemia? (4)
A
- coronary artery diameter and tone
- collateral blood flow
- perfusion pressure
- heart rate (duration of diastole)
24
Q
How many types of atherosclerotic lesions are there?
A
6 main types
25
What is Type 1 atherosclerotic lesion?
- coronary artery is at lesion-prone location
| - adaptive thickening of smooth muscle in the intima layer
26
What is Type 2 atherosclerotic lesion?
- macrophage foam cells begin to accumulate
27
What is Type 3 atherosclerotic lesion?
- preatheroma formed (fatty streak)
| - small pods of extracellular lipid
28
What is Type 4 atherosclerotic lesion?
- atheorma established
| - core of extracellular lipid
29
What is Type 5 atherosclerotic lesion?
- fibroatheroma
| - fibrous thickening of atheroma
30
What is Type 6 atheroscletotic lesion?
- complicated lesion
- thrombus likely
- fissure and haematoma into plaque common
31
How do drugs helps with ischaemic heart disease? (2)
1. Drugs DECREASE myocardial oxygen demand by reducing cardiac workload;
- reduce heart rate
- reduce myocardial contractility
- reduce afterload
AND
2. increase supply of O2 to ischaemic myocardium
32
What are the main RATE LIMITING drugs for ischaemic heart disease which reduce heart rate? (3)
1. Beta adrenoceptor antagonists
2. Ivabradine
3. Ca channel blocker
33
What are the main vasodilator drugs used for ischaemic heart disease? (2)
1. Ca channel blockers
| 2. Nitrates (oral or sublingual)
34
What are other medication which are not necessarily rate limiting or vasodilators but are also used to treat ischaemia? (3)
1. K channel blockers
2. Aspirin/ Clopidogrel/ Ticagrelor (first is aspirin and others used if patient allergic or intolerant)
3. Cholesterol lowering agents (HMG CoA reductase inhibitors, fibrates)
35
What 2 Beta Blockers are used to treat ischaemic heart disease? (2)
- Bisoprolol
| - Atenolol
36
What are beta blockers?
Reversible antagonists of the Beta 1 and Beta 2 receptors
37
What do newer beta blockers do? (how to they act?)
- they are cardioselective acting primarily on Beta 1 receptors
- these agents block the physiological responses to adrenaline and noradrenaline (sympathetic nervous system)
38
What are 3 major determinants of myocardial oxygen demand?
1. heart rate
2. contractility
3. systolic wall tension
39
Why do Beta blockers allow improved perfusion of the subendocardium?
By increasing diastolic perfusion time (if heart relaxed for longer then more blood flows into myocardium)
40
What is the function of beta blockers in terms of cardiac function? (6)
1. decrease heart rate
2. decrease force of myocardial contraction
3. decrease cardiac output
4. decrease velocity of contraction
5. decrease blood pressure
6. protect cardiomyoctes from oxygen free radicals formed during ischaemic episodes
41
How do beta blockers act?
- reduce heart rate, reduce force of contraction and reduce blood pressure
- increase exercise threshold at which angina occurs and so move balance point at which demand for O2 outstrips the supply of oxygenated blood
- threshold reset at which angina starts
42
What are the main drugs used as SECONDARY prevention of cardiovascular disease? (4)
1. aspirin (75mg daily)
2. ACE inhibitor (for stable angina and diabetic patients)
3. Statin treatment
4. High BP treatment
43
What is meant by a rebound phenomena?
- sudden cessation/ stopping of beta blocker therapy may cause MI
- never stop beta blockers immediately (unless emergency), but instead gradually
44
Who is at risk for a rebound phenomena? (2)
- men over 50 receiving beta blocker treatment for other reasons
- patients with angina
45
What are contraindications for the use of beta blockers? (When would we NOT use Beta Blockers as a treatment option) (5)
1. asthma
2. peripheral vascular disease (relative contraindication)
3. Raynauds Syndrome
4. Heart failure (dependent on sympathetic drive)
5. Bradycardia or Heart block patients (if Beta blockers over done)
46
What is Raynauds Syndrome?
- medical condition which causes spasm of arteries
- leads to reduced blood flow
- occurs typically in fingers (but can also happen in toes)
47
What are adverse drug reactions to beta blockers? (5)
1. tiredness/fatigue
2. lethargy (lack of energy, sleepiness, nonactivity)
3. impotence (erectile dysfunction)
4. bradycardia
5. bronchospasm
48
Are beta blockers generally primarily pharmacodynamic?
Yes
49
When do beta blockers cause hypotension in drug-drug interactions?
when used with other hypotensive agents
50
When do beta blockers cause bradycardia in drug-drug interactions? (2)
when used with other rate limiting drugs such as
- Verapamil
- Diltiazem
(both used to treat high BP)
51
When do beta blockers cause cardiac failure in drug-drug interactions? (3)
When used with negatively inotropic agents such as:
1. Verapamil
2. Diltiazem
3. Disopyramide (Na channel blocker for ventricular tachycardia)
52
What happens if beta blockersa are mixed with NSAIDs?
NSAIDs antagonise antihypertensive actions (stop beta blockers from working)
53
What effect can beta blockers have on diabetics?
-can exagerrate and mask hypoglycaemic actions of insulin or oral hypoglycaemics (patients on diabetic medication)
54
Why are beta blockers difficult to manage in many patients?
- used to treat heart failure at times but can also make heart failure worse (can be difficult to find right balance)
- has to be administered at right dose and in the right moment
55
Overall, which drugs should beta blockers be avoided to mix with? (4)
1. Verapamil (for high BP)
2. Diltiazem (for high BP)
3. Disopyramide (na channel blockers)
4. NSAIDs
56
What are the main 3 Ca channel blockers used to treat ischaemic heart disease? (4)
1. Diltiazem
2. Verapamil
3. Amlodipine
4. Nifedipine
57
How do Ca channel blockers work?
Prevent Ca influx into myocytes and smooth muscle lining arteries and arterioles by blocking L- type Ca channel and relieve angina symptoms by relaxing heart muscle (and arteries)
58
What are the 2 main properties of Ca channel blockers?
1. rate limiting (reduce heart rate, vascular tone, afterload and myocardial work load and force of contraction)
2. Vasodilating (may produce reflex tachycardia or coronary vasodilation)
59
Which Ca channel blockers are rate limiting? (2)
- verapamil
| - diltiazem
60
Which Ca channel blockers are vasodilating? (2)
- nifedipine
| - amplidipine
61
What type of nifedipine should NEVER be used to treat ischaemic heart disease?
Nifedipine Immediate Release
62
Why should nifedipine immediate release never be used? (2)
Rapidly acting vasodilatory Ca channel blockers like nifedipine immediate release may cause acute Mi or stroke
63
What complications can Ca channel blocker like nifedipine immediate release cause post MI?
may increase morbidity and mortality in patients with impaired l. ventricular function
64
What complications can a channel blocker like nifedipine immediate release cause in unstable angina patients?
Dihydropyridines may increase infarction rate and death rate and likeliness in unstable patient
65
What are the main adverse drug reactions to Ca channel blockers?
1. ankle oedema (affects 15-20% of patients and doesn't respond to diuretics)
2. headache
3. flushing
4. palpitation
66
In which Ca channel blocker especially is ankle oedema common in?
amlodipine (oedema doesn't seem to respond to diuretics)
67
What are the 3 main nitrovasodilators used to treat ischaemic heart disease?
1. glyceryl trinitrate (GTN)
2. isosorbide mononitrate
3. isosorbide dinitrate
68
In what ways is glyceryl trinitrate (GTN) administered? (3)
1. sublingual
2. buccal (between gum and cheeks)
3. transdermal
69
In what ways are isosorbide mononitrate and isosorbide dinitrate administered?
Tablets; sustained release formulation
70
When is GTN usually taken by patients? (2)
- when angina pain starts coming on
- used for RAPID angina treatment
- when patient knows they are performing an activity that can trigger angina (preventive/prophylaxis)
- can be used frequently and prophylactically
71
What is GTN syncope?
- reaction to GTN by some patients which causes patient to collapse and faint suddenly
- causes arteriodilation and venodilation, reduces cardiac return and causes a sudden drop in BP
- patient loses consciousness
72
When is isosorbide mononitrate and dinitrate usually taken by patients?
- if patient is stable on Ca channel blockers and Beta blockers
- these give further anginal relief
- used as prophylaxis
- given once a day since sustained release formulation
73
How do nitrovasodilators work?
- relax almost ALL smooth muscle by releasing NO
| - NO stimulates release of cGMP which produces smooth muscle relaxation
74
How do nitrates relieve angina? (4)
1. arteriolar dilatation; reduce cardiac afterload and thus myocardial work and O2 demand
2. peripheral venodilation and so reduces venous return, cardiac preload and thus myocardial workload
3. relieve coronary vasospasm
4. redistributing myocardial blood flow to ischaemic areas of myocardium
75
Do nitrates reduce mortality?
There is no evidence that they do reduce mortality
76
What are 3 types of nitrovasodilators?
1. GTN
2. Oral nitrates
3. Intravenous nitrates
77
What is the main advantage to GTN administration of nitrates?
They bypass first pass metabolism and provide rapid treatment
78
What is the main difference between use of GTN and oral nitrates in terms of pain relief delivery?
- GTN provides rapid relief since given frequently
| - Oral nitrates given once a day for sustained release formulation (can take longer to metabolise than GTN)
79
What is the main advantage of oral nitrates?
- tolerance to nitrate created by nitrate release within 16 hours and overnight they don't work
- this allows system recovery before nitrate begins to work again the next day
80
When are intravenous ntitrates used?What are they used in combination with?
- used to treat UNSTABLE angina
| - used in combination with heparin
81
What is the main problem for nitrate therapy?
tolerance to the effects of nitrate can develop rapidly (resistance)
82
How can tolerance to nitrate therapy be overcome? (2)
1. giving asymmetric doses of nitrate 8am and 2pm
| 2. using sustained release preparation which incorporates a "nitrate free period"
83
What are adverse drug reactions to nitrates? (2)
1. headache (increase dose slowly to avoid this)
| 2. hypotension ( GTN syncope)
84
What is the main K channel opener?
1. Nicorandil
85
How does K channel opener, Nicorandil, work?
- activates "silent" K channels
| - entry of K into cardiac myocytes inhibits the Ca influx and so has a negative inotropic action
86
Why is Nicorandil less commonly used now?
Because it can lead to bowel ulceration (can cause Chron's disease)
87
What is the name of a selective sinus node channel inhibitor?
Ivabradine
88
How does Ivabradine work?
- slows the diastolic depolarisation slope of SA node
| - reduces heart rate and myocardial O2 demand
89
What is the main antiplatelet agent used to treat ischaemic heart disease? What dose?
Aspirin; 75-150mg
90
What is aspirin the potent inhibitor of?
- inhibitor of platelet thromboxane production
- thromboxane naturally stimulates platelet aggregation (clumping) and vasoconstriction
- platelet aggregation is main pathogenesis of angina, unstable angina and acute MI
91
What are the main pros of aspirin used as antiplatelet therapy? (2)
1. cheap
| 2. effective
92
In what patients is aspirin as antiplatelet therapy effective in?
reduces incidence of coronary artery disease outcomes in patients who:
- have a heart rate of 70bpm or greater and normal sinus rhythm
- symptomatic treatment of chronic stable angina in adults
93
When is antiplatelet therapy used?
- in adults unable to tolerate or with a contra-indication to the use of beta blockers
- in combination WITH beta blockers in patients inadequately controlled with optimal beta-blocker dose
94
In what patients does antiplatelet therapy worsen outcomes for?
in patients with bradycardia
95
Daily use of aspirin is used to treat which 3 main ischaemic heart conditions?
1. acute MI
2. unstable angina
3. as secondary prevention
96
What is the most common cause of admission with a GI bleed?
low dose aspirin
97
How does Clopidogrel work?
- inhibits ADP receptor activated platelet aggregation (prevents clots)
- prophylaxis of atherosclerotic events in PVD (peripheral vascular disease) and acute coronary syndrome
98
Can Clopidogrel cause GI bleeding?
- Yes, but possibly to lower extent than aspirin
- can still cause bleeding especially in elderly
- patients may experience indigestion ,anaemia and secondary MI before GI bleed detected
99
What 2 new agents are used instead of clopidogrel to minimise risk of bleeding?
1. Prasugrel
2. Ticagrelor
(platelet aggregation inhibitor)
100
What are the 3 main cholesterol lowering agents used for ischaemic heart disease?
1. Simvastatin
2. Pravastatin
3. Atorvastatin
101
How do cholesterol lowering agents work?
- They are HMG CoA reductase inhibitors which are most effective cholesterol lowering agents
- can reduce mortality post MI
102
What is the link between heart disease and lowering cholesterol?
Reducing cholesterol, reduced risk of coronary heart disease, MI and stroke
103
What is the treatment regimen for treating STABLE ischaemic heart disease? (10)
1. Beta blockers
2. rate limiting Ca channel blockers
3. Aspirin (antiplatelet therapy)
4. Statin (cholesterol lowering)
5. Ca channel blocker (dihydropiridine)
6. Nitrovasodilators (nitrates)
7. Nicorandil (K channel blocker)
8. Ivabradine or Ranolazine (Sinus node inhibitor)
9. Clopidogrel (platelet inhibition)
10. Refer for cardiology work up for possible stenting
104
```
In terms of:
- vasodilation
- heart rate
- myocardial contractility
Describe the effect of short acting nitrates (sublingual) on these.
```
- increase vasodilation
- no effect on heart rate
- no effect on myocardial contractility
105
```
In terms of:
- vasodilation
- heart rate
- myocardial contractility
Describe the effect of beta blockers on the these.
```
- no effect on vasodilation
- decrease heart rate
- decrease myocardial contractility
106
```
In terms of:
- vasodilation
- heart rate
- myocardial contractility
Describe the effect of long acting nitrates on these.
```
- increase vasodilation
- no effect on heart rate
- no effect on myocardial contractility
107
```
In terms of:
- vasodilation
- heart rate
- myocardial contractility
Describe the effect of Ca channel blockers on these.
```
- increase vasodilation
- decrease heart rate
- decrease myocardial contractility
108
What is the primary cause of angina?
transient myocardial ischaemia (often due to vasospasm of coronary arteries)
109
What are the newest approaches to treating myocardial ischaemia? (4)
1. Preconditioning with Nicorandil
2. Late Na current inhibition (Ranolazine)
3. Sinus node inhibition (Ivabradine)
4. Metabolic Modulation ( Trimetazidine)
110
What is a SCAD?
- spontaneous coronary artery dissection (tear in coronary artery)
- spontaneous tear causes blood to flow in between 3 layers of artery wall creating a bulge inwards
- this narrows or blocks artery which means it stops blood flow to heart muscle leading to ischaemia
111
What is 1st line treatment for a SCAD ( form of ischaemia)?
Angina relief through SHORT ACTING NITRATES plus Beta blockers and Ca channel blockers
112
What drugs can be used along as 2nd line treatment for SCAD (form of ischaemia)? (5)
- ivabradine
- long acting nitrates
- nicorandil (stable angina)
- ranolazine (chronic angina)
- trimetazidine (anti-ischaemic)
113
What invasive medical procedures can be considered for SCAD (form of ischaemia)? (2)
- angioplasty
/ PCI stenting
- CABG
114
What is 1st line prevention methods for SCAD? (2)
- lifestyle management
| - control of risk factors
115
What is 2nd line drug prevention for SCAD? (3)
1. aspirin (if intolerant then use Clopidogrel which is platelet inhibitor)
2. statins
3. ACEIs or AREs
