Lipid Lowering Drugs Flashcards
(16 cards)
What drugs are considered ‘lipid lowering therapies’?
Statins/ HMG-CoA Reductase Inhibitors
Bempedoic Acid
PCSK9 Inhibitors
Fibrates
Bile Acid Sequestrants
Nicotinic Acid
What are some modifiable risk factors for the development of atheromatous disease?
Raised LDL cholesterol in plasma
Reduced HDL cholesterol in plasma
Hypertension
Diabetes Mellitus
Cigarette Smoking
Obesity
Physical inactivity
Raised C-Reactive Protein
Raised Coagulation Factors (e.g factor VII and fibrinogen)
How do HMG-CoA reductase inhibitors (aka Statins) reduce plasma LDL?
Statins interfere with the hepatic synthesis of cholesterol, they do this by competitively inhibiting the action of the enzyme HMG-CoA reductase, which catalyses the conversion of HMG-CoA into mevalonic acid, a metabolic precursor to cholesterol. Thus inhibition of this enzyme results in decreased hepatic production of cholesterol, and subsequently decreased levels of LDL within the blood, as low density lipoproteins transport cholesterol to the arteries through the bloodstream.
What drugs are considered statins?
Atorvastatin
Rosuvastatin
Simvastatin
Fluvastatin
Pravastatin
What daily dosages of which statins are used as ‘high intensity statin therapy’, and how effective is each dose at reducing LDL cholesterol?
Atorvastatin:
20mg - 43% reduction in LDL
40mg - 49%
80mg - 55%
Rosuvastatin:
10mg - 43%
20mg - 48%
40mg - 53%
Simvastatin:
80mg - 42%
What daily dosages of which statins are used as ‘medium intensity statin therapy’, and how effective is each dose at reducing LDL cholesterol?
Atorvastatin:
10mg - 37%
Fluvastatin:
80mg - 33%
Rosuvastatin:
5mg - 38%
Simvastatin:
20mg - 32%
40mg - 37%
What daily dosages of which statins are used as ‘low intensity statin therapy’, and how effective is each dose at reducing LDL cholesterol?
Fluvastatin:
20mg -21%
40mg - 27%
Pravastatin:
10mg - 20%
20mg - 24%
40mg - 29%
Simvastatin:
10mg - 27%
What are the main ‘pleiotropic’ effects of statins
Improved endothelial function
Reduced vascular inflammation
Reduced platelet aggreability
Increased neovascularisation of ischaemic tissue
Increased circulating endothelial progenitor cells (cells that play a role in vascular regeneration and repair)
Stabilisation of atherosclerotic plaques (less vulnerable to rupture)
Anti-thrombotic actions
Enhanced fibrinolysis (degradation of fibrin)
Why is it recommended that statins be administered at night?
As the majority of cholesterol biosynthesis occurs during sleep
Fill in the blank…
It is estimated that statins produce a …% reduction in risk of mortality
30%
What are the potential adverse effects of statins use?
Mild effects: Myalgia, GI disturbance, raised concentration of liver enzymes in plasma, insomnia, rash
Rare but potentially serious effects: Skeletal muscle damage (Myositis or rhabdomyolysis if severe) & angio-oedema
How do proprotein convertase substilisin/kexin type 9 (PCSK9) inhibitors reduce plasma LDL?
PCSK9 is a proprotein convertase enzyme, primarily produced in the liver, that binds to LDL receptors, causing their degradation and preventing them from being recycled. When there are less LDL receptors expressed by the liver, less LDL can be taken up from the bloodstream, leading to high plasma LDL levels.
PCSK9 inhibitors are monoclonal antibodies (synthetic man-made proteins that mimic the actions of human antibodies by targeting specific cells) that essentially prevent PCSK9 from binding to LDL receptors, thus preventing their degradation and lowering plasma LDL levels
What are some examples of PCSK9 inhibiting drugs?
Evolocumab
Alirocumab
Both are delivered via subcutaneous injection every two weeks or every month
When are PCSK9 inhibitors indicated?
To treat primary hypercholesterolaemia or mixed dyslipidaemia in patients who have not responded adequately to other appropriate measures
To treat established atherosclerotic cardiovascular disease - in combination with the maximum tolerated dose of a statin with or without other lipid lowering therapies, or alone if a statin is contraindicated or not tolerated
How does Azetimibe work?
It inhibits the absorption of cholesterol in the duodenum by blocking the transport protein NPC1L1, and is used to supplement statins in lipid lowering therapy
How do bile acid resins work?
They sequester bile acids in the intestine, preventing re-absorption. Examples of bile acids resins include:
Colestyramine & Colestipol
They do not change HDL plasma concentrations and also cause an unwanted increase in triglycerides
