Hyperlipidaemia and therapeutic approaches Flashcards
Hyperlipidaemia
high LDL cholesterols
Dyslipidaemia
High levels of HDL-cholesterol
Chylomicrons
Transport TGs/cholesterol from intestine via lymph to blood
VLDL
High TG content, lipoprotein lipase converts VLDL Tis to FFA
LDL
high cholesterol content
Hypercholesterolemia
Elevated LDL-c
Lipid functions
Energy storage Intracellular signalling Base for steroid hormone synthesis vit D synthesis Insulation
Triglycerides
Glycerol backbone with 3x FFAs
Excess calories converted to Tis and transpired to fat cells for storage
Cholesterol
Steroid alcohol found in animal tissues
Mainly synthesised in liver
precursor of steroids, bile acids and vit D
Maintains cell membranes
Lipoproteins
Bind lipids and facilitate transport in water
Cell surface receptors are different for different apolipoproteins
Function of low cholesterol lipoproteins
Deliver endogenous TAG to peripheral tissues
Optimal levels of LDL-c
<1.8mmol/L
Optimal levels of cholesterol
<4.4mmol/L
Optimal levels of triglycerides
<1.1mol/L
Causes of primary dyslipidaemias
- Genetic mutations
- Familial hypercholesterolemia most common
- Typically presents in children
Causes of secondary dyslipidaemias
- Diet
- Obesity
- Diabetes
- Hypothyroidism
- Alcohol
- CKD
- Drugs
Management of dyslipidaemias
- Lifestyle - reduce total and saturated fat intake, weight loss, exercise
- Statins: HMG-COA reductase inhibitors
- Secondary pt first-line treatment is lifestyle changes
- Plant sterols (stop body absorbing cholesterol) lower LDL-C and increase HDL-C
Statins MOA
HMG-coA reductase inhibitors (important in cholesterol synthesis)
Side effects of statins
Kidney problems
Muscle degeneration and ache
Paraesthesia
PCSK9
Proprotein convertase subtilise/kexin type 9
Binds LDL for degeneration in lysosomes
Determines LDL-c concentration
This needs to be inhibited to allow LDL to be taken up from blood
Ezetimibe
Impairs intestinal uptake of dietary and bile conjugated cholesterol
Used as add on to statins
Side effects ezetimibe
Fatty stools
Statin target organ
Liver
Statin MOA
Inhibit HMG COA - involved in cholesterol synthesis
This causes liver cells to make more LDL receptors = increased clearance of LDL from blood stream
Side effects statins
Muscular side effects and GI disturbances
Ezetimibe target organ
GI tract
MOA ezetimibe
Selective cholesterol absorption inhibitor - inhibits cholesterol at brush border at small intestine
Increases LDL cholesterol uptake into cells = decreased blood levels
Ezetimibe side effects
Fatigue, diarrhoea, abdo pain
Colestyramine target organ
GI tract
Colestyramine MOA
Binding bile acids, reducing reabsorption which reduces conversion of cholesterol into bile acids
Colestyramine side effects
Intestinal obstruction and acidosis
Fibrates MOA
Activate PPAR to break down triglycerides
Fibrates side effects
Myositis-like syndrome if renal function impaired
Nicotinic acid MOA
Reduces production of TGs and VLDL which are converted to LDL in blood
Side effects nicotinic acid
vasodilatation - skin flushing
methylcellulose MOA
Attracts water into colon = softer and bulkier stool
Swelling ins Atomach = reducing hunger
