Cholesterol Flashcards
1
Q
statins
A
MOA
- competitive inhibition HMG COa reductase, the rate limiting step in liver cholesterol synthesis
- > increase in gene expression for LDL receptor on hepatocytes
- > increased LDL clearance from circulation
- decrease apolipoprotein B secretion
- > decreases VLDL production decreased
- > low VLDL decreases plasma triglycerides
SE
- Myalgia/myopathy/rhabdo
- > dose, age and illness related
- > myopathy most common within 1 month/dose increase
- > effect on ocular muscles causes diplopia
- Transaminase elevation
- > uncommon and resolves with lower dose
- Transient GI symptoms
- Headache
- Insomnia/nightmares
- Dizziness
- Necrotising autoimmune myopathy
- > rare
- > CK extremely elevated
- > HMG-CoA reductase autoantibodies
Precautions
- severe illness
- > myopathy, rhabdo, renal failure
- kidney disease
- > increases risk of rhabdo (lower dose)
- liver disease
- > lower dose
- elderly
- > higher risk of rhabdo
- Pregnancy and breast feeding
- > not safe
2
Q
bile acid sequestrants
A
Cholestryamine and colestipol
MOA
- complex to bile acids in gut and prevent enterohepatic circulation
- > increased hepatic bile salt production
- > depletion of cholesterol pool
- > increased expression of LDL receptor and clearance from circulation
- increase in VLDL as compensatory change to lowered LDL
- > increase plasma triglycerides
SE
- steatorrhoea and GI distress
- malabsorption fat soluble vitamins and drugs
- hepatotoxicity
3
Q
nicotinic acid
A
MOA
- inhibits synthesis of VLDL
- > decrease IDL and LDL
- increase HDL as HDL donates cholesterol ester to IDL to produce LDL
SE
- rash
- pruritus
- flushing
- hepatotoxicity
4
Q
fibrates
A
Gemfibrozil
MOA
- activates PPARs to induce lipoprotein lipase
- > inhibit lipolysis and hepatic uptake of fatty acids
- > decrease hepatic VLDL production
- > decrease LDL
SE
- raised LDL in patients with hypercholesterolaemia (dysfunctional LDL receptors)
- dyspepsia
- GI distress
5
Q
ezetimibe
A
MOA
- inhibits absorption of dietary and biliary cholesterol at brush border
- > decreases hepatic LDL pool
- > increase LDL receptor expression
- > increased LDL clearance
SE
- well tolerated
- fatigue
- athralgia/myalgia
- diarrhoea
- transaminitis
6
Q
PCSK9 inhibitor
A
evolocumab, alirocumab
MOA
- monoclonal antibodies block PCSK9 mediated breakdown of LDL receptors on hepatocytes
- > increases LDL receptors available for cellular uptake of LDL
- > decreases LDL circulation
Subcutaneous injections (monthly/fortnightly)
SE
- injection site reactions
- rash, pruritis, urticaria
- well tolerated and conflicting evidence for other side effects (eg. muscle and neurotoxicity)
7
Q
non pharm lipids
A
- increase plant sterol enriched foods (milk, margarine, cheese)** = most effective for LDL
- increase physical activity and reduce weight ** = most effective increase HDL
- reduce unsaturated and transfats
- substitute for mono and polyunsaturated
- increasing fibre
- decrease alcohol
8
Q
pharm lipids
A
Indications
- indication = >15% CVD risk (high), existing CVD or dyslipidaemia
- lifestyle first line in mild to moderate CVD absolute risk
Algorithm first line -statins -strong evidence for primary and secondary second line -statin + ezetimibe -good evidence for secondary prevention -no evidence for primary third line -statin + PCSK9 inhibitor -good evidence secondary -no evidence for primary fourth line -statin + exetimibe/PCSK9 + fibrate or bile acid binder -limited evidence can't tolerate statins -ezetimibe monotherapy -limited evidence
