3.2 Cholesterol Pharmacology Flashcards
What is the relationship between cholesterol and CHD risk?
Positive
What is the primary target to prevent CHD?
LDL cholesterol
What are the pro-atherogenic effects of Ox-LDL?
Inhibits macrophage motility
Induces T cell activation and VSMC division
Toxic to endothelial cells
Enhances platelet aggregation
Effect of obesity on cholesterol, triglycerides and HDL cholesterol
Cholesterol and triglycerides increase
HDL cholesterol decrease
What do statins do?
Inhibit cholesterol synthesis in hepatocytes
Increase clearance of IDL and LDL
Decrease production of VLDL and LDL
What enzyme do statins block?
HMG-CoA reductase
What are the indications for statins?
CV risk prevention
Familial hypercholesterolaemia
What is a mechanism of action of statins?
Increased synthesis of LDL receptor
Decreases serum cholesterol
What are some ADRs of statins?
Liver function - Increased transaminase levels
Muscle - Myopathy, diffuse muscle pain
Can sometimes have elevated CK can lead to rhabdomyolysis
Seen when statins used in higher doses and in combination with cyclosporin, gemfibrozil and erythromycin and niacin
GI complaints, arthralgias and headaches
What are some secondary benefits of statin treatment?
Anti-inflammatory
Plaque reduction
Improved endothelial cell function
Reduced thrombotic risk
What is a problem with cerivastatin?
Its structure caused drug-drug interaction
What is the receptor that fibrates act on?
Peroxisome Proliferator-Activated Receptor agonist
Increases production of lipoprotein lipase
What do fibrates do?
Reduces triglyceride production
Some reduction in LDL, may increase HDL
What is the mechanism of action of fibrates?
Increases fatty acid uptake and oxidation
Reduces triglyceride levels
Increases LDL particle size and HDL-C levels
Direct vascular effects
What are the indications for fibrates?
Adjunctive therapy to diet
Hypertriglyceridmia
Side effects of fibrates?
GI upset, cholelithiasis, myositis
Abnormal liver function test
Contraindications of fibrates?
Hepatic of renal dysfunction
Pre-existing gall bladder disease
What does nicotinic acid do?
Reduces VLDL
Increases HDL
Reduces coronary events
How does nicotinic acid exert its lipid lowering effects?
Inhibition of lipoprotein a synthesis
Adverse effects of nicotinic acid
Flushing, itching and headache
Hepatotoxicity, GI
Activation of peptic ulcer
Hyperglycaemia and reduced insulin sensitivity
Contraindications for nicotinic acid
Active liver disease or unexplained raised LFTs
Peptic ulcer disease
What type of drug is ezetimibe?
Cholesterol lipase inhibitor
What is the main mechanism of action of ezetimibe?
Selectively inhibits intestinal cholesterol absorption
Decreases intestinal delivery of cholesterol to liver
Increase expression of hepatic LDL receptors (so remove more LDL cholesterol)
Decrease cholesterol content of atherogenic particles
Why does ezetimibe have less adverse side effects?
Ezetimibe and active metabolite circulate enterohepatically
Delivers agents back to site of action
Limits systemic exposure
What are some ADRs for ezetimibe?
Headache
Abdominal pain
Diarrhoea
What is a problem with combination statin and fibrate therapy?
Increased risk for myopathy and rhabdomyolysis
Fibrates may impair statin metabolism so higher concentrations of statins in blood can lead to more side effects
What is a new type of lipid lowering drug?
PCSK9 inhibitors - monoclonal antibodies
Stops LDL receptors from being internalised
What could someone who didn’t want to take drugs do to lower lipids?
Plant sterols
Positive: Fish oils, fibre, vit C and E, alcohol (HDL)
Negative: Dietary cholesterol and fat, alcohol (TG)
What should be given to all people that have had an MI?
Statin
How can cardiovascular risk be calculated?
Internet calculator eg Qrisk2
What are some lifestyle changes for prevention of CVD?
Cardioprotective diet Physical activity Weight management Alcohol consumption Smoking cessation
What drug is usually prescribed for primary prevention of CVD?
Atorvastatin
