5. Lipid Lowering Drugs Flashcards
Which form of lipid carries the highest risk for cardiovascular disease?
LDL - Low density lipoprotein
Why is LDL considered the most dangerous form of fat?
-It carries cholesterol from the liver to the cells
-Which can lead to the accumulation of cholesterol in the walls of arteries
-Leading to atherosclerosis
Why is HDL “good” for you?
-It helps remove cholesterol from the bloodstream
-Transporting it back to the liver for excretion
-Reducing the risk of cholesterol buildup and atherosclerosis
What are high levels of ApoA1 associated with?
High levels of ApoA1 are associated with a lower risk of cardiovascular disease.
What is ApoA1 (apolipoprotein A1)?
-ApoA1 is the primary protein component of HDL (high-density lipoprotein)
-It plays a crucial role in reverse cholesterol transport, where it helps remove cholesterol from the arteries and transport it back to the liver for excretion or recycling
What is ApoB (apolipoprotein B)?
-ApoB is the primary protein found in LDL (low-density lipoprotein) and other atherogenic lipoproteins like VLDL (very-low-density lipoprotein)
-It is essential for the transport of cholesterol and triglycerides to tissues.
What are high levels of ApoB associated with?
High levels of ApoB-containing lipoproteins are associated with an increased risk of cardiovascular diseases due to the potential for cholesterol buildup in the arteries.
What is lipoprotein A?
-Lipoprotein(a) is a lipoprotein variant that consists of an LDL particle bound to a specific protein called apolipoprotein(a)
-Elevated Lp(a) levels are genetically determined and not significantly affected by lifestyle factors, unlike other lipoproteins like LDL and HDL.
What are high levels of lipoprotein A associated with?
High levels of Lp(a) are considered an independent risk factor for cardiovascular diseases, as it can contribute to the formation of arterial plaques and promote inflammation
Describe the formation of an atherosclerotic plaque in the arteries (from LDL circulation til monocyte activation)
1: Circulating LDL gains access to subendothelial space
2: LDL particles undergo oxidation, a process that makes them more atherogenic (capable of contributing to plaque formation). Oxidized LDL is recognized as harmful by the immune system.
3: The oxidized LDL triggers the release of pro-inflammatory cytokines, including IL1 and MCP1
4: Monocytes migrate through the endothelial layer (intima) and enter the subendothelial space, where they differentiate into macrophages
Describe the formation of an atherosclerotic plaque in the arteries (from macrophage formation til plaque enlargement)
5: Macrophages engulf oxidised LDL, accumulating it, transforming them into foam cells
6: Smooth muscle cells from the middle layer of the blood vessel (media) migrate into the intima and begin to proliferate.
7: As foam cells accumulate, smooth muscle cells, lipids, and necrotic (dead) cells start to form a primitive atherosclerotic plaque.
8: Over time, the plaque enlarges, developing a fibrous cap made of collagen and smooth muscle cells. The plaque pushes into the vessel lumen (the interior space of the blood vessel), narrowing the artery and reducing blood flow.
What is a cause of primary dyslipidaemia, and its prevalence amongst the population?
-Familial hypercholesterolaemia
-1/250
What percentage of males with Familial Hypercholesterolaemia will have symptomatic heart disease by the age of 50?
50%
Give some visual symptoms of hypercholesterolaemia
-Cholesterol deposits around the eye
-Tendon Xanthomata
-Lipaemia Retinalis
-Milky serum
Give some causes of secondary dyslipidaemias
-Medications, eg beta blockers, thiazide diuretics, protease inhibitors, oral contraceptives
-Diabetes mellitus
-Obesity
-Hypothyroidism
-CKD
Give some non pharmacological treatments of dyslipidaemia
-Cardioprotective diet
-Weight loss
-Physical activity
-Reduce alcohol consumption
-Smoking cessation
Give some pharmacological treatments of dyslipidaemia
-HMG CoA reductase inhibitors (statins)
-Fibrates
-Cholesterol absorption inhibitors
-Omega fatty acids
-Nicotinic acid
What are HMG CoA reductase inhibitors also known as?
Statins
Describe the mechanism of action of statins/HMG CoA reductase inhibitors
-Block HMGCoA reductase in the mevalonate pathway, preventing formation of a cholesterol precursor, effectively reducing the endogenous production of cholesterol
-Lower cholesterol synthesis raises the number of LDL receptors on hepatocytes, incresasing LDL cholesterol uptake
-They may also modestly increase HDL
Give comparison in the use of short vs long acting statins in the treatment of dyslipidaemia
-Short-acting statins are often prescribed for patients with relatively low cholesterol levels or when cost is a significant concern, as generics for short-acting statins are more widely available.
-Long-acting statins are generally prescribed for patients who need a more consistent effect throughout the day or have more complicated lipid profiles, including very high cholesterol levels.
Why give different length of action statins?
-Cholesterol is primarily synthesized at night, so short-acting statins work best when taken before bed. In contrast, long-acting statins provide continuous inhibition of cholesterol synthesis, making them suitable for 24-hour control.
-Long-acting statins are typically easier to adhere to, as they don’t require precise timing, which is useful for patients with busy or unpredictable schedules.
-Long-acting statins are often more effective in patients with higher cholesterol levels, as they maintain steady drug concentrations, providing consistent cholesterol-lowering effects.
-Some patients may experience fewer side effects with one type over the other, depending on how their body metabolizes the drug.
Give examples of short acting and longer acting statins
Short acting: Simvastatin, lovastatin
Long acting: Atrovastatin
When are the statins used clinically?
Treatment of
-Primary hyperlipidaemia
-Secondary hypercholesterolemia (eg in Diabetes mellitus)
-Secondary prevention of MI and stroke
Give the adverse effects associated with statins
-Muscle related: Myalgia, myopathy and rhabdomyolysis
-Elevated liver enzymes
-Increased risk of diabetes
-GI disturbance
