lipid lowering drugs Flashcards
What are the lipid lowering drugs used?
- HMG CoA Reductase Inhibitors (targets cholesterol)
- “Statins” - PCSK9 Inhibitors (targets cholesterol for pts intolerant to statins)
- Fibrates/Fibric acid derivatives (targets triglycerides)
- Omega-3-acid ethyl esters (targets triglycerides)
- Niacin (targets triglycerides)
- Bile acid binding resins (targets cholesterol)
- Inhibitors of intestinal sterol absorption
-Ezetimibe
Exogenous pathway of cholesterol transport
- Triglycerides in chylomicrons will be hydrolysed by lipoprotein lipase and the tissues will take up remaining free fatty acid
- Chylomicron remnants will bind to hepatocyte receptors and undergo endocytosis
- Cholesterol will be stored, oxidised to bile acids or secreted in bile unaltered
Endogenous pathway of cholesterol transport
- Cholesterol and newly synthesised triglycerides are transported from the liver to adipose tissue and muscle cells via VLDL
- Triglycerides will be hydrolysed to lipoprotein lipase and lipoprotein particles becomes LDL
- LDL will be taken up by cells by LDL receptors via endocytosis that recognise LDL apolipoproteins
- Cholesterol returns to plasma as HDL particles
Classification of Hyperlipoproteinaemia
Type 1: Familial Hyperchylomicronemia
Type 2a: Familial Hypercholesterolemia
Type 2b: Familial Combined Hyperlipidaemia
What is the problem in Type 1: Familial Hyperchylomicronemia?
Deficiency of lipoprotein lipase
What is the problem in Type 2a: Familial Hypercholesterolemia?
Decreased no. of LDL receptors
What is the problem in Type 2b: Familial Combined Hyperlipidaemia?
Overproduction of VLDL by liver
What is the lipoprotein elevated in Type 1?
Chylomicron
What is the lipoprotein elevated in Type 2a?
LDL
What is the lipoprotein elevated in Type 2b?
LDL + VLDL
Is there atherosclerotic risk in Type 1?
No
Is there atherosclerotic risk in Type 2a?
High risk
Is there atherosclerotic risk in Type 2b?
High risk
MOA of HMG CoA reductase inhibitors
- inhibit HMG CoA reductase inhibitors -> decrease cholesterol synthesis
- upregulate LDL receptors on cell surfaces -> more LDL will be endocytosed and LDL-cholesterol will be internalised
Statins are best given at ____. Why?
Night.
Basal HMG CoA reductase activity is highest at night, hence giving statins at night can maximally inhibit the enzyme
Adverse effects of statins
Affects liver function
Rhabdomyolysis and myopathy
MOA of PCSK9 inhibitors
- blocks PCSK9
- reduces degradation of LDL receptors by lysozymes
- decrease endocytosis of LDL -> less LDL-cholesterol internalised
Contraindications using statins
Pregnant, nursing women, children, teenager (affects neurodevelopment of child, foetus)
Adverse reactions using PCSK9 inhibitors
Injection site inflammatory response
Nasopharyngitis and Sinusitis
Contraindications using PCSK9 inhibitors
Patients with hypersensitivity reactions
Omega-3-acid ethyl esters is not indicated for
Type 1 hyperchylomicronemia
MOA of bile acid binding resins
- Resins bind to bile acids and bile salts
- Decrease in bile acids conc. will cause increase conversion of cholesterol to bile acids in hepatocytes
- Decrease intracellular cholesterol
- Cause increase uptake of LDL into cells -> decrease plasma LDL levels
Adverse reactions of bile acid binding resins
GI effects
Impaired absorptions: vitamin A, D, E, K
MOA of Inhibitor intestinal sterol absorption (ezetimibe)
inhibits cholesterol transport protein
Does ezetimibe remain effective in the absence of dietary cholesterol?
Yes, it prevents bile salts from re-entering intestine
