Lecture 11 IHD Flashcards
What causes IHD?
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
When does Ischaemia occur?
How does Ischaemia often present?
oxygen demand of the myocardium (heart muscle) exceeds the supply
chest pain - central in chest but can radiate to arms, neck and jaw
What can cause chest pain?
angina or myocardial infarction
due to release of potassium ions, H+ and adenosine that stimulate nociceptors
What is the epidemiology of IHD?
2013 IHD resulted in 7 million deaths
21,000 cases/year in UK
prevalence over 55-year olds
What are the modifiable risk factors of IHD?
high blood pressure
diabetes
smoking
high-cholesterol
What are the non-modifiable risk factors of IHD?
advanced age
male gender
family history of IHD and/or heart disease
What are probable risk factors of IHD?
poor diet
obesity
chronic kidney disease
What are the risks of IHD to patients?
acute coronary syndromes including
NSTEMI - type of MI
STEMI - blockage of one of the main coronary arteries
unstable angina - pre-MI condition
When does acute coronary syndrome (ACS) present?
when the flow in the artery is suddenly blocked leading to ischaemia normally due to platelet rupture forming platelet clots
What is the problem with IHD?
can be untraceable by ECG unless they have had a previous MI or currently having ischaemia/MI
What is angina characterised by?
heavy or central crushing pain on exertion
relieved by rest
What are the different treatments for stable angina?
nitrates and calcium-antagonists - reduce cardiac work
statin - treat underlying condition
prophylaxis - anti-platelet drugs
What are the different treatments for unstable angina?
treat as if MI - DAPT (dual-antiplatelet therapy) and nitrates
What is the difference between stable and unstable angina?
stable - predictable pain on exertion
unstable - pain occurring with less and less exertion
What is the difference between STEMI/NSTEMI and unstable angina?
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
What is the clinical importance of raised troponin levels?
How is raised troponin levels tested for?
troponins are specific to cardiac muscle and raised in STEMI/NTEMI patients
they allow diagnosis of MI and indicate myocyte death
blood test
What is the overall aim of ischaemic treatments?
What happens if this is not achieved?
restore blood flow and quickly
necrosis of the myocardium will occur along with MI leading to heart failure
What are the four broader aims of IHD treatment?
reopen blocked arteries
reduce blood coagulability
control risk factors
reduce myocardial oxygen demand
How is blood flow restored to the heart?
percutaneous coronary intervention (PCI)
nitrates
How does PCI work?
widens the artery using dilation from within via the radial, brachial or femoral arteries
use a metallic stent often coated with anti-platelet drugs
What is the crucial door-to-balloon time in STEMI cases?
120 minutes
Why are treatments given before, during and after PCI?
risk of stent thrombosis ~1%
reduce the coagulability of blood to reduce risk
What is the treatment given to patients after PCI? What is the aim of this pharmacological treatment?
DAPT (dual anti-platelet therapy)
to keep the coronary plaques as stable as possible to avoid an acute blockage
What are the two approaches of pharmacological treatments?
symptomatic - reduce symptoms
prognostic - improve outcomes
What treatments can be given to patients suffering with IHD?
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
What is the primary mechanism of nitrates?
relaxation of smooth muscle in vasculature leading to reduced blood pressure and coronary vasodilation
reduces central venous pressure, preload (venodilation) and reduces cardiac work
When and who discovered nitrates?
Lauder Brunton 1867
What are the secondary effects of nitrates?
reduces cardiac work
redirection of flow towards ischaemic areas of heart muscle
improves coronary artery spasms
What are the adverse effects and disadvantages of nitrates?
hypotension - administer sitting down
headaches
tolerance - possibly depletion of -SH groups
no proof reduce mortality
What are the pharmacokinetics of GTN?
short acting
sublingual delivery effective within 1-2 minutes
inactivated by hepatic metabolism
effective 30 minutes
What are the pharmacokinetics of Isosorbide Mononitrate?
long acting
oral deliver twice a day
nitrate-free period overnight to avoid tolerance
What are the pharmacokinetics of CCB - Amiloride?
dihydropyridine - long elimination time given max once/day
What are the side effects of CCBs?
flushing and headache
verapamil - constipation (effect of GI nerves/smooth muscle)
What is the advantage of aspirin?
reduces mortality
reduces risk of future MI
How does aspirin work?
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
What are the risks of aspirin?
gastrointestinal bleeding
tinnitus and deafness (larger dose/overdose)
risk of self-poisoning
interacts and increases [warfarin]
What are the pharmacokinetics of aspirin?
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)
Give an example of an anticoagulant
What is their function?
Heparins - glycosaminoglycans found in mast cells and basophils
prevent venous thrombus and thrombus propagation
What is the mechanism of action of heparins?
activation of antithrombin IIIa which inactivates thrombin and factor Xa preventing the formation of a stable clot
What is a heparin antidote?
protamine sulphate
What is an adverse effect of heparins?
bleeding
Give examples of antiplatelet drugs
thienopyridines
clopidogrel (PLAVIX)
tricagrelor
Give example of an analgesic
What else can it be used for?
How does it work?
morphine
inducing euphoria and stop diarrhoea
binds to opioid (mu) receptors in the brain - Gi/Go coupled to ion channels
Define: Antiemetic
Give an example
anti-vomiting drug
metoclopramide
What are the side effects of morphine?
respiratory depression nausea and vomiting - acting on postrema (medulla) reduced gut tone and motility histamine release tolerance
What treatments are given for unstable angina?
What secondary treatments are given as preventatives?
DAPT
heparin
analgesics
planned PCI (once stable)
statins
ACE inhibitors
beta blockers
What treatments are given for NSTEMI?
DAPT + additional anti-platelet if unstable ECG
analgesics
PCI (72 hours)
What happens if you can’t complete PCI for STEMI patients within 120 minutes?
What should be noted about this treatment?
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
What treatments are given for STEMI?
PCI - 120 minutes
antiplatelet medications - aspirin and ticagrelor
ACE inhibitors and beta blockers - aid myocardial recovery
What is the mortality for a STEMI patient?
4.4% if reach hospital
30% do not make it to hospital
