Lecture 11 IHD

Question 1

What causes IHD?

Answer 1

when a fatty/fibrotic plaque (atherosclerosis) blocks the coronary artery lumen restricting blood flow (ischaemia) resulting in reduced nutrient supply to the tissues - oxygen and glucose

Question 2

When does Ischaemia occur?

How does Ischaemia often present?

Answer 2

oxygen demand of the myocardium (heart muscle) exceeds the supply
chest pain - central in chest but can radiate to arms, neck and jaw

Question 3

What can cause chest pain?

Answer 3

angina or myocardial infarction

due to release of potassium ions, H+ and adenosine that stimulate nociceptors

Question 4

What is the epidemiology of IHD?

Answer 4

2013 IHD resulted in 7 million deaths
21,000 cases/year in UK
prevalence over 55-year olds

Question 5

What are the modifiable risk factors of IHD?

Answer 5

high blood pressure
diabetes
smoking
high-cholesterol

Question 6

What are the non-modifiable risk factors of IHD?

Answer 6

advanced age
male gender
family history of IHD and/or heart disease

Question 7

What are probable risk factors of IHD?

Answer 7

poor diet
obesity
chronic kidney disease

Question 8

What are the risks of IHD to patients?

Answer 8

acute coronary syndromes including
NSTEMI - type of MI
STEMI - blockage of one of the main coronary arteries
unstable angina - pre-MI condition

Question 9

When does acute coronary syndrome (ACS) present?

Answer 9

when the flow in the artery is suddenly blocked leading to ischaemia normally due to platelet rupture forming platelet clots

Question 10

What is the problem with IHD?

Answer 10

can be untraceable by ECG unless they have had a previous MI or currently having ischaemia/MI

Question 11

What is angina characterised by?

Answer 11

heavy or central crushing pain on exertion

relieved by rest

Question 12

What are the different treatments for stable angina?

Answer 12

nitrates and calcium-antagonists - reduce cardiac work
statin - treat underlying condition
prophylaxis - anti-platelet drugs

Question 13

What are the different treatments for unstable angina?

Answer 13

treat as if MI - DAPT (dual-antiplatelet therapy) and nitrates

Question 14

What is the difference between stable and unstable angina?

Answer 14

stable - predictable pain on exertion

unstable - pain occurring with less and less exertion

Question 15

What is the difference between STEMI/NSTEMI and unstable angina?

Answer 15

unstable angina patients require GTN relief, have normal ECGs and do not have raised troponin levels

STEMI/NSTEMI patients do not require GTN relief, have abnormal ECGs and have raised troponin levels

Question 16

What is the clinical importance of raised troponin levels?

How is raised troponin levels tested for?

Answer 16

troponins are specific to cardiac muscle and raised in STEMI/NTEMI patients
they allow diagnosis of MI and indicate myocyte death
blood test

Question 17

What is the overall aim of ischaemic treatments?

What happens if this is not achieved?

Answer 17

restore blood flow and quickly

necrosis of the myocardium will occur along with MI leading to heart failure

Question 18

What are the four broader aims of IHD treatment?

Answer 18

reopen blocked arteries
reduce blood coagulability
control risk factors
reduce myocardial oxygen demand

Question 19

How is blood flow restored to the heart?

Answer 19

percutaneous coronary intervention (PCI)

nitrates

Question 20

How does PCI work?

Answer 20

widens the artery using dilation from within via the radial, brachial or femoral arteries
use a metallic stent often coated with anti-platelet drugs

Question 21

What is the crucial door-to-balloon time in STEMI cases?

Answer 21

120 minutes

Question 22

Why are treatments given before, during and after PCI?

Answer 22

risk of stent thrombosis ~1%

reduce the coagulability of blood to reduce risk

Question 23

What is the treatment given to patients after PCI? What is the aim of this pharmacological treatment?

Answer 23

DAPT (dual anti-platelet therapy)

to keep the coronary plaques as stable as possible to avoid an acute blockage

Question 24

What are the two approaches of pharmacological treatments?

Answer 24

symptomatic - reduce symptoms

prognostic - improve outcomes

Question 25

What treatments can be given to patients suffering with IHD?

Answer 25

``` nitrates - glyceryl trinitrate (GTN), isosorbide mononitrate antiplatelet drugs - aspirin calcium channel blockers - amlodipine potassium channel activators - nicorandil analgesics - morphine statins/PCSK9 inhibitors beta blockers - propranolol ACE inhibitors - ramipril ```

Question 26

What is the primary mechanism of nitrates?

Answer 26

relaxation of smooth muscle in vasculature leading to reduced blood pressure and coronary vasodilation reduces central venous pressure, preload (venodilation) and reduces cardiac work

Question 27

When and who discovered nitrates?

Answer 27

Lauder Brunton 1867

Question 28

What are the secondary effects of nitrates?

Answer 28

reduces cardiac work redirection of flow towards ischaemic areas of heart muscle improves coronary artery spasms

Question 29

What are the adverse effects and disadvantages of nitrates?

Answer 29

hypotension - administer sitting down headaches tolerance - possibly depletion of -SH groups no proof reduce mortality

Question 30

What are the pharmacokinetics of GTN?

Answer 30

short acting sublingual delivery effective within 1-2 minutes inactivated by hepatic metabolism effective 30 minutes

Question 31

What are the pharmacokinetics of Isosorbide Mononitrate?

Answer 31

long acting oral deliver twice a day nitrate-free period overnight to avoid tolerance

Question 32

What are the pharmacokinetics of CCB - Amiloride?

Answer 32

dihydropyridine - long elimination time given max once/day

Question 33

What are the side effects of CCBs?

Answer 33

flushing and headache | verapamil - constipation (effect of GI nerves/smooth muscle)

Question 34

What is the advantage of aspirin?

Answer 34

reduces mortality | reduces risk of future MI

Question 35

How does aspirin work?

Answer 35

irreversibly inhibits the COX-1 enzymes through acetylation on platelets preventing conversion of arachidonic acid into thromboxane A2 reducing platelet aggregation platelets have a lifetime of 10 days and are produced by the bone marrow

Question 36

What are the risks of aspirin?

Answer 36

gastrointestinal bleeding tinnitus and deafness (larger dose/overdose) risk of self-poisoning interacts and increases [warfarin]

Question 37

What are the pharmacokinetics of aspirin?

Answer 37

weak acid - protonated in stomach allowing to pass through lining of mucosa major site of absorption - ileum rapidly hydrolysed to salicylate in tissue by esterases in liver (or plasma)

Question 38

Give an example of an anticoagulant | What is their function?

Answer 38

Heparins - glycosaminoglycans found in mast cells and basophils prevent venous thrombus and thrombus propagation

Question 39

What is the mechanism of action of heparins?

Answer 39

activation of antithrombin IIIa which inactivates thrombin and factor Xa preventing the formation of a stable clot

Question 40

What is a heparin antidote?

Answer 40

protamine sulphate

Question 41

What is an adverse effect of heparins?

Answer 41

bleeding

Question 42

Give examples of antiplatelet drugs

Answer 42

thienopyridines clopidogrel (PLAVIX) tricagrelor

Question 43

Give example of an analgesic What else can it be used for? How does it work?

Answer 43

morphine inducing euphoria and stop diarrhoea binds to opioid (mu) receptors in the brain - Gi/Go coupled to ion channels

Question 44

Define: Antiemetic | Give an example

Answer 44

anti-vomiting drug | metoclopramide

Question 45

What are the side effects of morphine?

Answer 45

``` respiratory depression nausea and vomiting - acting on postrema (medulla) reduced gut tone and motility histamine release tolerance ```

Question 46

What treatments are given for unstable angina? What secondary treatments are given as preventatives?

Answer 46

DAPT heparin analgesics planned PCI (once stable) statins ACE inhibitors beta blockers

Question 47

What treatments are given for NSTEMI?

Answer 47

DAPT + additional anti-platelet if unstable ECG analgesics PCI (72 hours)

Question 48

What happens if you can't complete PCI for STEMI patients within 120 minutes? What should be noted about this treatment?

Answer 48

give patient a clot-buster to stimulate breakdown of stable fibrin clots, e.g. streptokinase can't use antiplatelets and clot buster drugs at the same time

Question 49

What treatments are given for STEMI?

Answer 49

PCI - 120 minutes antiplatelet medications - aspirin and ticagrelor ACE inhibitors and beta blockers - aid myocardial recovery

Question 50

What is the mortality for a STEMI patient?

Answer 50

4.4% if reach hospital | 30% do not make it to hospital