Ischaemic heart disease

Question 1

What is IHD?

Answer 1

Umbrella term-
coronary artery disease /IHD/ coronary heart disease all describe the same condition
occurs when a fatty plaque blocks the coronary artery lumen- ischemia

Question 2

Whats the progression of coronary atherosclerosis?

Answer 2

foam cells-> fatty streak-> intermediate lesions-> atheroma-> complicated lesion or rupture-> fibrous plaque

Question 3

What are the risk factors for IHD?

Answer 3

Nonmodifiable- age, male sex, positive family history

Modifiable- high bp, diabetes, smoking, raised cholesterol

Question 4

What are the acute coronary syndromes?

Answer 4

unstable angina
non-ST elevated myocardial infarction (NSTEMI)
ST elevation myocardial infarction (STEMI)
STEMI= a sudden, complete blockage of the artery
NSTEMI= partial/temporary blockage of the artery
-syndrome presents itself when the plaque ruptures
-stable angina= not an ACS

Question 5

What is angina?

Answer 5

central crushing pain triggered by exertion- relieved by rest

Question 6

What is unstable angina and how do you treat it?

Answer 6

Unstable angina- pain occurs with less and less exertion- including at rest

• DAPT
• nitrates

Question 7

What is stable angina and how do you treat it?

Answer 7

triggered by exertion, goes away with rest

• nitrates
• calcium antagonists
• statins- treat underlying cause
• prophylaxis- antiplatelet drug

Question 8

ECG and blood features of unstable angina

Answer 8

GTN relief- yes
ECG normal- yes (not normal in an episode)
Troponin raised- no

Question 9

ECG and blood features of STEMI and NSTEMI

Answer 9

GTN relief- no
ECG normal- no
Troponin raised- yes
troponin raised= indicated dying myocytes

Question 10

What are the broad aims for the treatment of ischaemia?

Answer 10

Restore blood flow quickly

• reopen blocked arteries
• reduce coagulability of the blood- antiplatlet, aspirin, heparins
• control risk factors- statins etc
• reduce myocardial oxygen demand- ACE-Is and diuretics

Question 11

What is PCI?

Answer 11

Percutaneous coronary intervention non-surgical technique
insert a catheter into the radial/brachial artery- track the catheter under fluoroscopic guidance into the coronaries- widens the artery from within
use of a stent with a balloon

Question 12

What sort of drugs are normally attached to the stent?

Answer 12

Drug coated- inhibit cell regrowth

rapamycin or taxol

Question 13

Why is stenting bespoke?

Answer 13

Using angiograms- can see the coronary arteries- see where the stent needs to go

Question 14

What drugs need to be taken after stenting?

Answer 14

Dual action antiplatelet therapy
clopidogrel or ticagrelor 
-continue for a year after stenting 
-adverse effects- risk of bleeding 
benefits: anti-inflammatory- not understood

Question 15

What are symptomatic treatments- give examples

Answer 15

Reduce the symptoms
-reduce strain on the heart- increase vasodilation
nitrates (glyceryl nitrate - short-acting) (isosorbide mononitrate- long lasting)
aspirin and antiplatelet drugs
Ca channel blockers- amlodipine
K channel activators- nicorandil
analgesia- morphine

Question 16

What are prognostic treatments- give examples

Answer 16

Alleviate further negative outcomes
aspirin 
statins/ pcsk9 inhibitors 
beta blockers 
ACE inhibitors 
anti-inflammation approaches being developed

Question 17

Nitrates- primary and secondary mechanisms

Answer 17

First line agent= GTN (nitroglycerin)
primary mechanism: relax smooth muscle & the veins- main effect on the larger muscular arteries and coronary vasodilation
secondary mechanism: reduce cardiac work, redirection of flow towards ischaemic areas of heart muscle, improves coronary artery spasm
*mechanism- GTN metabolism releases NO- activates GC- increased cGMP- leads to smooth muscle relaxation

Question 18

What are the adverse effects of nitrates, and what are their pharmacokinetic features

Answer 18

Possibly hypotension
headaches
tolerance can occur
-GTN is inactivated by hepatic metabolism
-length of effect= 30 minutes
-isosorbide mononitrate- orally administered 2 x a day- nitrate free period at night to avoid tolerance

Question 19

Features of calcium channel blockers and their pharmacokinetics

Answer 19

Reduce ischaemia but not mortality
non-selectively blocks contraction of smooth muscle
-verapamil selective to the heart- nifedipine more selective to smooth muscle
-few sides fx: flushing and headache due to vasodilation
-amlodipine has a long elimination time

Question 20

How does aspirin work?

Answer 20

Reduces mortality and risk of future heart attack
inhibits COX1 receptors on platelets- reduces platelet aggregation
irreversibly acetylates cox enzymes
prevents conversion of arachidonic acid to thromboxane 2
aspirin can last as long as 10 days- how long it takes for platelets to replenish
Risk- GI bleeding

Question 21

What are the pharmacokinetics of aspirin?

Answer 21

given orally
weak acid
ileum is site of absorption
side fx: gastric bleeding, deafness/ tinnitus (larger/ over doses)
risk of self-poisoning
some are resistant- no genetic test available yet
interacts with warfarin- increases conc of warfarin- effects platelets

Question 22

How do anticoagulants/ anti-platelet approaches work?

Answer 22

Inhibit clotting factors in the clotting cascade
heparins: enoxaparin- activates antithrombin 3a which inactivates thrombin and factor Xa- prevent formation of a stable clot
side fx: bleeding
anti-platelet approach: clopidogrel

Question 23

What analgesics are given in ACS?

Answer 23

opiates and antiematics
morphine= usually well tolerated if given correctly
side fx: nausea/ vomiting

Question 24

What are the treatments for unstable angina?

Answer 24

DAPT
heparins 
analgesics
secondary prevention: 
statins, ace inhibitors or beta blockers 
once stabilized: elective (planned) PCI

Question 25

What are the treatments for NSTEMI?

Answer 25

Antiplatelet and antithrombotic therapy
analgesics
PCI within 72 hrs to determine lesions severity and suitability for stenting or a bypass

Question 26

What are the treatments for STEMI?

Answer 26

Primary PCI at local heart attack centre
if unable- use a clot busting drug intravenously
antiplatelet medications
life long medications:
aspirin, antiplatelet, ACE-Is, beta blockers to aid myocardial recovery

Question 27

Examples of IHD personalisation

Answer 27

1. Measure individual platelet reactivity
2. Angiograms- individualized map of coronary arteries
   - can use computer modelling to do this- different angles and branches and sites of lesions
3. Anti-inflammatory approach- future potential treatment- been proven that inhibition of inflammation prevents repeat heart attacks and reduces all cause mortality