Lipid lowering therapy - Dawes Flashcards
What are the plasma lipids
cholesterol
Triglycerides
Fatty acids
Phospholipids
Cholesterol subtractions
Total cholesterol LDL cholesterol - Adverse effects HDL cholesterol - Beneficial effects Triglycerides - Adverse vascular effects - Pancreatitis
Polar outer core makes them soluble with triglyceride inner core
What organ is central to cholesterol metabolism
liver
Why lower cholesterol? primary and secondary
Primary - reduction of vascular events - small effect on mortality Secondary - Large beneficial effects - Decrease CVS mortality and morbidity - TC 1mmol/L reduction --> dec 25% vascular events The more you lower cholesterol the more you decrease the risk of future cardiovascular events
Why is cholesterol not the sole most important risk factor?
You mustn’t just lower cholesterol its synergistic with all other risk factors e.g. smoking, hypertension, diabetes
History
Examination
Investigations
H - End organ damage (primary and secondary prevention) Exam - BP, Xanthoma, xanthelasmata Investigations - U+E's - Fasting cholesterol / LDL / HDL / Trigs - Glucose - ECG
Who to treat in terms of primary and secondary patients
Secondary - Angina, MI - CVA - PVD Diabetics (high vascular risk)
Primary prevention
- CVS risk > 30% over 10 years (NZ)
Problems with the US and UK thresholds for treating people with a lower CVS risk than us
NNT ratio very large, so would have to treat about 100 people over 5 years to stop one from having an adverse cardiovascular event, when the other 99 will be exposed to the side effects of the drug.
Targets and treatments (number 1 and two)
total cholesterol <4mmol/L
LDL <2mmol/L
Triglycerides <2.2mmol/L
Treatment
- lifestyle changes
- Drugs
Summary of the drugs you can use and which type of cholesterol they can alter
Statins (simvistatin, atorvistatin) - dec TC, Dec LDL, Inc HDL, Dec Trigs Fibrates (Bezafibrate) - very dec trigs, inc HDL Ezetimibe - dec TC and LDL Nicotinic acid - dec Trig
Statins
- indications
primary prevention - High CVS risk - Dibetes - Familial hypercholesterolemia Secondary prevention - Pervious MI, angina, CVA, TIA, PVD
Statins
- MoA
Inhibitors of HMGCoA reductase
block synthetic pathway of production of cholesterol in hepatocytes
Knock on effect, intracellular levels within hepatocytes fall, however the hepatocytes still need cholesterol for daily business e.g. making bile acids, production of setoid hormones, So hepatocytes produce more LDL surface receptors which mops up more circulating LDL, which is incorporated into the cell and reduces circulating LDL cons.
Statins also block the production of isoprenoids
Pharmacy only funds two statin drugs here, why can this be a disadvantage?
Simvistatin is metabolised in the liver by the CYP3A4 enzyme, atorvistatin also metabolised by this but not as much (usually good alternative). Therefore need to be really careful when prescribing the drugs that inhibits the action of CYP3A4 --> can get side effects from dug build up. Watch for: - Amiodarone - Verapamil - Diltiazem - erythromycin
Statins - side effects
myalgias
Myositis
Rhabdomyalasis
Deranged LFT
–> Teratogenic
Spectrum of skeletal muscle aches and pains from mild to significant damage of muscles with release of myoglobin into the blood stream which is a nephrotoxin so can get AKI, very rare, rhabdomyolysis can be potentially life threatening
If get myalgias then try another statin, decrease dose or stop drug.
What is the gene that codes for the enzymes that mediates hepatic uptake of drugs?
Inc incidence of SLCO1B1 (chromosome 12)
encodes organic anion transporting polypeptide OATP1B1
Mediates hepatic uptake of drugs.
