Week 206 - Myocardial Infarction Flashcards
What type of inheritance pattern does Familial Hyperlipidaemia have?
Autosomal Dominant
List 3 clinical signs of hyperlipidaemia.
1) Xanthelasma
2) Tendon xanthomata
3) Corneal arcus
What is considered the ideal total cholesterol blood level?
<5mmol/L
What is considered to be a very high cholesterol level?
> 7.8mmol/L
Which chromosome holds the gene responsible for Familial Hypercholesterolaemia?
Chromosome 19
What is the main aim of non-drug treatment for hypercholesterolaemia?
Maintaining a lean body weight
What lifestyle changes should be encouraged to manage hyperlipidaemia?
Reduce – fat intake, alcohol consumption
Smoking cessation
Avoid thiazides, oestrogens and non-selective B-blockers
Increase exercise
What is the most potent pharmacological treatment for hypercholesterolaemia?
Statins
In which groups of patients should you be particularly careful when prescribing statins?
Children
Women of reproductive age
cholesterol is source of steroid hormones so reducing cholesterol could also reduce steroid hormone production
When should statins be taken and why?
In the evening > cholesterol synthesis is most active at night
What is the reasonably common alternative pharmacological treatment for hypercholesterolaemia/hyperlipidaemia?
Fibrates
What do fibrates (fibric acid derivatives) do?
Reduce blood triglyceride levels by:
-Decreasing VLDL production in liver (therefore reducing triglyceride carrier potential)
-Modestly increase HDL levels
Have NO effect of LDL levels
What is the function of a lipoprotein?
To carry/transport lipids in the blood
Describe the process of atherosclerotic plaque formation.
Damage/insult on the endothelial lining which releases factors such as ADP and *** causing platelets and macrophages to adhese and aggregate. Lipids, calcium and cellular debris accumulate too and smooth muscle cells begin to form a fibrous cap over the plaque > plaque is now unable to disperse.
What do macrophages become within an atherosclerotic plaque?
Foam cells
How does Aspirin work as an antithrombotic drug?
It irreversibly inhibits platelet cyclo-oxygenase-1 (COX-1) through acetylation. COX-1 catalyses thromboxane and prostaglandin production > reduces thromboxane A2 and prostaglandin
What is prostacyclin (PG12)?
A vasodilator and platelet inhibitor produced by platelets and vascular endothelium.
What clinical sign is virtually diagnostic of heterozygous familial hypercholesterolaemia?
Tendon Xanthomata > occurs in ~70% of all affected individuals
What two major clinical signs occur around the eyes of many individuals with familial hypercholesterolaemia?
Xanthelasma and corneal arcus (premature)
What are yellow, fatty plaque lesions associated with hyperlipidaemia that occur on the body in areas besides the eyes?
Xanthomas (xanthelasma is the most common form of xanthoma)
Why is chromosome 19 associated with Familial hypercholesterolaemia?
Because the LDL receptor is coded for on chromosome 19 and it is dysfunction of any of the 5 steps involved in LDL receptor function that can result in the condition
How is familial hypercholesterolaemia best managed?
With a statin. High dose atorvastatin has been proven to reverese intimal thickening that occurs in FH
How do statins work in the treatment of hypercholesterolaemia?
They inhibit HMG CoA in the liver – the rate limiting step in cholesterol synthesis. Increase the removal of LDL and IDL( by inc. their receptors), decrease the production of LDL and VLDL. Slightly increase HDL
Why are fibrates contraindicated in gallstone disease?
They themselves can cause gallstone formation by increasing cholesterol excretion via bile
Why should fibrates be used with caution in renal impairment?
May increase creatinine levels
List the main contraindications of fibrates.
Severe hepatic impairment, hypoalbuminaemia, primary biliary cirrhosis, gallstone disease, nephrotic syndrome, pregnancy and breast-feeding
