Cholesterol Pharmacology Flashcards
Why is cholesterol management important
Cholesterol and LDL levels are major risk factors for CVD
What are indications for cholesterol pharmacological therapy
Primary prevention
Secondary prevention
Of cardiovascular disease
Who require statin therapy for primary prevention
10yr CV risk >10% on QRISK2 assessment
CKD with eGFR <60
T1DM with: >40yo, >10yrs diabetic, established nephropathy, other CVD risk factors
What treatment is given for primary prevention
Artorvastatin 20mg
How do you screen for hyperlipidaemia
Full lipid profile: Total cholesterol HDL Non-HDL cholesterol TAG
Who require treatment for secondary prevention
Anyone with established CVD:
IHD
Stroke
Peripheral arterial dienes
What treatment is given for secondary prevention
80mg artorvastatin
What is mechanism of action of statins
Inhibit HMG-CoA reductase
Inhibit cholesterol synthesis at hepatocytes
Reduce LDL synthesis
Increase LDL uptake (low cholesterol in hepatocytes causes increased LDLR expression)
Thus lower serum cholesterol
What are secondary benefits of statins
Anti inflammatory
Reduce plaque formation
Improve endothelial function
What are side effects of statins
GI disturbance
Myopathy: Muscle aches, myositis, rhabdomyolysis, raised CK
Liver impairment: raised transaminases
What are PK properties of statins
30-80% absorption
5-30% systemic availability
CYP450 metabolism (some types)
Taken at night: time of cholesterol synthesis
What monitoring is required for statins
LFTs
Baseline, 3 monthly, 12 monthly
What is mechanism of action of fibrates
PPAR alpha agonist Stimulate lipoprotein lipase Significant Decrease in TAG levels Mild decrease in LDL Mild increase in HDL
Give examples of fibrates
Bezafibrate
What are indications of fibrates
Mixed hyperlipidaemia:
Hyperlipidaemia with low HDL
Hypertriglyceridaemia
Combination with statins
What caution is required when given in combination with statins
Increased risk of myopathy, rhabdomyolysis
What are side effects of Fibrates
GI disturbance
Myopathy
Liver impairment - raised transaminases
Cholelithiasis
What are contra indications of fibrates
Liver impairment
Renal impairment
Pre existing gall bladder disease
What is mechanism of action of Ezetimibe
Inhibit cholesterol receptors in enterocytes
Selective inhibition of cholesterol absorption
Reduced intestinal delivery to hepatocytes
Increased LDL R expression by hepatocytes
What are indications of Ezetimibe
Monotherapy:
statin therapy contraindicated or not tolerated
Combination:
Failed to achieve adequate reduction on statins
What are side effects of Ezetimibe
GI disturbance headache
Give examples of nicotinic acid
Niacin
What is mechanism of action of niacin
Inhibit VLDL release from hepatocytes
Reduced LDL
Increased HDL
What are indications of niacin
Best agent to raise HDL
What are side effects of niacin
Flushing, itching
Hepatotoxicity
Activation of peptic ulcer
Give examples of PCSK9 Inhibitors
Alirocumab
What is mechanism of action of PCSK9 Inhibitors
Inhibit PCSK9 activity
PCSK9 normally binds to LDL-LDLR complex and promotes destruction than recycling
Thus increase LDLR recycling
Increased LDL uptake by hepatocytes
