Lipid- modifying therapy Flashcards
Learning outcomes
- Outline lifestyle modifications that can favourably modify a person’s lipid profile
- List the different classes of lipid modifying agents and describe their mode of action and potential adverse effects
- Understand which patients require lipid-lowering treatment and how treatment targets are set
Lifestyle interventions for hypertension
- Stop smoking
- Achieve a healthy body weight i.e. BMI 20-25 kg/m2–if ideal body mass cannot be achieved, losing 5% can have a significantly helpful effect on blood pressure.–A healthy waist line measurement is also important
- Eat a healthy diet–diet high in fruit/vegetables and low in fat can reduce blood pressure.
- Restrict salt intake -avoid salt added at the table and choose foods low in salt-<1500 mg sodium per day is ideal for adults
- Moderate alcohol intake (no more than 14 units per week)
- Take adequate exercise
- Discourage excessive caffeine intake
Lifestyle for lipids- key messages
Mimimise dietary fat–Total fat <30% energy; saturated fat <7%; cholesterol < 300 mg/day; replace saturated fats with mono/poly-unsaturated fats
•Wholegrain varieties of starchy food
•Reduce sugar intake
•At least 5 x fruit/vegetable portions per day
•At least 2 portions of fish per week (caution –pregnancy)
•At least 4-5 portions of unsalted needs, seeds and legumes / week
•Exercise•Achieve healthy weight
•Healthy alcohol intake
•Smoking cessation
Drugs in common use
- HMG-CoA reductase inhibitors (Statins)
- Ezetimibe
- PCSK-9 inhibitors
- Fibrates
- Colesevelam
- Omega-3 fish oil
Statins
Inhibit HMG-CoA reductase > Reduced synthesis of cholesterol > Up-regulation of LDL-receptors > Movement of LDL into cells > Reduce circulating LDL
Statin potency and adverse effects
Rosuvastatin> Atorvastatin> Simvastatin> Pravastatin
Generally given at night
Extensively metabolised
Rosuvastatinand pravastatin are hydrophilic
Good at lowering LDL
- Generally well tolerated
- Muscle pain-more rarely myositis/rhabdomyolysis
- Gastrointestinal disturbance
- Liver enzyme abnormalities
Ezetimibe
Niemen pick C1 like 1 protein- E. stops this moving cholesterol into cells
Good at lower LDL cholesterol
Major adverse effects
- Generally well tolerated
- Gastrointestinal disturbance
- Liver enzyme abnormalities
PCSK9- inhibitors and adverse effects
- Monoclonal antibodies against proprotein convertase subtilisin-like/kexin-9 (PCSK-9)
- Names: Evolocumab, Alirocumab
- Fortnightly or monthly subcutaneous injection
- Good at lowering LDL
Much more expensive than statins or ezetimibe
- Generally well tolerated
- Nasopharyngitis
- Back pain
- Flu-like symptoms
Fibrates and fibrates in use
•Activate the nuclear transcription factor PPARα especially in liver and muscle
–Increased transcription of genes for lipoprotein lipase, apo-A1 and apo-A5
–Mainly reduce VLDL and therefore triglycerides
–A wide range of other effects
- Many fibrates are in production
- Gemfibrozil generally not used due to risk of interactions
- Fenofibrate and bezafibrate used most commonly in UK
- Good at lowering triglycerides
Major adverse effects- generally well tolerated
•Gastrointestinal disturbance
•Muscle pain (more rarely myositis / rhabdomyolysis)
•Care when combined with statins
Colesevelam
- Bile acid-binding resin
Reduces LDL-C production and Plasma LDL-C
Adverse effect is gastrointestinal disturbances
Omega-3 marine triglycerides
- Mechanism of action for lipid-lowering unclear•Wide range of non-lipid actions
- Reasonable at lowering triglycerides
- Usually no adverse effects
Optimal control of lipids
•Statin first line for overwhelming majority
•Consider fibrate first line if triglycerides very high
•Who to treat
–All secondary prevention
–All familial hypercholesterolaemia
–Primary prevention + 10 year CV risk ≥10%
Target example- •NICE–Non-HDL-C reduction of >40%–LDL-C reduction of >50% in familial hypercholesterolaemia
