Angina and myocardial infarction Flashcards
What do we do to manage an angina attack?
Reassure patient
Call 999
If sublingual GTN doesn’t help a MI maybe in progress.
Chewable aspirin + MUST tell ambulance it has been given.
High flow O2
What is the three usual causes of angina perctoris?
Restriction (usually incomplete) in blood supply to working heart muscle.
Partial occlusion of blood vessels
> atheroma
> thrombus
Vasospasm in coronary arteries
> overly reactive vessels
> drugs e.g. cocaine, smoking
Severe anaemia
How does an atheroma form?
Endothelium damaged
Cholesterol accumulation
- oxidation
Monocyte invasion
- convert to macrophages, phagocytose cholesterol to become foam cells
Foam cell degeneration
- Deposition of atherosclerotic plaque, increases stiffness at margin and narrows artery.
How is HDL associated with coronary heart disease and heart attacks?
HDL is strongly associated with a -ve risk of heart attack incidence to due increasing HDL/LDL ratio.
How do platelets have a central role in the formation of an atheroma?
When platelets are activated when they come in contact with the tunica intima, they shed microparticles which attract monocytes.
Monocytes then proliferate and differentiate into phagocytes
Phagocytes consume cholesterol/lipoprotein and become foam cells.
Foam cells die and deposit atheroscleoritc plaque in artery.
Name two HMG CoA reductase inhibitors
Lovastatin and atorvastatin
- decrease liver cholesterol synthesis
- increase VLDL and LDL receptor expression to decrease blood LDL levels
What are some of the side effects of HMG CoA reductase inhibitors?
Muscle cramps
Gi tract disturbances
Malabsorption of lipid soluble vitamins (ADEK) and lipid soluble drugs.
In which patients are HMG CoA reductase inhibitors seen to have the best efficacy?
In patients with known cardiovascular disease.
What is the mechanism of action of ezetimibe?
inhibits absorption of cholesterol at the brush border of the small intestines
This means more is uptaken from the circulation into the liver cells.
When is eztimibe most commonly used?
In statin intolerant patients or as an adjunct to statin treatment.
Name two fibrates?
Bezafibrate Ciprofibrate
What is the mechanism of action of fibrates?
Agonists of PPAR alpha receptor.
This leads to increased lipoprotein lipase activity which decreases VLDL.
Increases HDL via apolipoprotein A
Decreased hepatic triglyceride secretion.
Increased B oxidation in the liver.
What is the main use for fibrates?
Mainly used for hypercholesterolaemia.
What are some side effects of fibrates?
Mild stomach upset
Gallstones
Name two Bile acid binding agents
Cholestipol & cholestyramine
What is the mechaism of action of Cholestipol & cholestryamine?
Bind to bile acid in the gut leading to increased cholesterol loss due to
Decreased enterohepatic recirculation of bile.
Increased synthesis of bile salts by liver
Decreased liver cholesterol
Increased LDL receptor expression leading to greater LDL uptake
What is the main uses for Bile acid binding agents such as Cholestipol?
Hyperlipidaemias.
What are some side effects of bile acid binding agents such as cholestipol?
GI tract disturbances
Increase in VLDL and triacylglyceride synthesis
Malabsorption of lipid soluble vitamins
Malabsorption of lipid soluble drugs.
What is the mechanism of action of Nitrate in the treatment of angina?
Increase the production of NO.
NO is an endothelium derived relaxing factor.
NO stimulates guanylate cyclase to produce cGMP.
cGMP leads to increased myosin light chain phosphatase activity
Myosin light chains in the smooth muscle in the tunica media are dephosphorylated, relaxing the smooth muscle.
Why cant we orally administer NO?
Has a half life of a minute and undergoes nearly 100% first pass metabolism in the liver.
What are the actions of NO?
Venous vasodilation
- reduction in preload which reduces the stress put on the heart so the cardiac muscles need less energy.
Arterial dilation
- reduced arterial resistance so heart has to beat less hard.
Coronary artery dilation
- increased blood flow to the cardiac myocytes which in turn means more O2.
Some antiplatelet/antithrombotic effects - can break down atheroma / thrombus which could be causing blockage.
What are some ways in which nitrates are administered?
Via buccal mucosa
Transdermal patches (long acting)
Alkyl nitrates (abused as poppers).
What are some side effects of nitrates?
Headache, flushing (vasodilation), palpitations
What drugs may Nitrates have an adverse effect with when combined?
Drugs for impotence (such as viagra) has potential to cause hypotensive crisis.
