hyperlipidaemia and lipid lowering drugs Flashcards
what is the two function of cholesterol
-give cell rigidity (becomes a problem is cell is too rigid)
-importance component in bile acids which allows recirculation of cholesterol
how is excess cholesterol excreted
trapped in GIT then excreted via faeces
what are lipoproteins
breaks off proteins combining cholesterol
what is the difference between high density (HDL) and low density lipoproteins (LDL)
HDL = has more protiens, mops up cholesterol from various organs and walls of arteries (slows athersceolosis)
LDL = deposits cholesterol into tissues
what is the cause of primary dyslipidaemia
combination of dietary and genetic factors - familial hypercholesteolaemia
what is the cause of of secondary dsylipidaemia
consequence of other condition
-diabetes melitius
-alcoholism
-renal disease
what is the non-pharmacological treatment
-cardioprotective diet
-weight loss
-physical activity (increases HDL)
-decrease alcohol consumption
-smoking cessation
when would pharmacological treatment be used to treat dyslipidaemia
-only if there is a history/family history of CV disease
-many risk factors
-poor lipid profile
how many types of hyperlipidaemia are there
I, IIa, IIb, III, IV, V
what types of hyperlipidaemia is chylomicrons levels elevated
Type I and Type V
What type of hyperlipideamia is beta very low density lipoproteins elevated
Type III
What type of hyperlipideamia is LDL elevated
Type IIa, IIb
what is the difference between Type IIa and Tyoe IIb hyperlipidaemia
In both LDL is elevated, in IIb VLDL is elevated also
which two types of hyperlipideamia has high atherosclerosis
IIa and IIb
which type of hyperlipidaemia has the highest levels of triglycerides
Type I - Chylomicrons elevated
which type of hyperlipideamia can be treated with statins
type IIa, IIb, V
which type of hyperlipideamia can be treated with fibrates
IIb,III,IV,V
which type of hyperlipideamia can be treated with ezetimibe
IIa
which type of hyperlipideamia can be treated with nicotinic acid
IIb
which type of hyperlipideamia can be treated with niacin & fish oil
V
which type of hyperlipideamia isn’t treated with parmaceutical
Type I
which type of hyperlipideamia has the highest levels of cholesterol
IIa, IIb, III
What is familial hypercholesterolaemia (FH) and how is it caused
The reduction in receptor mediator clearance of LDL
Due to mutation of LDLR, APOB or PCSK9 gene
autosomal co-dominant
what is the risk of developing FH
1/250
what is the lipid profile of FH
elevated LDL, Cholesterol , triglycerides
what are the physical signs of FH
-Cholesterol deposits in the eyes (Xanthelasmas)
-white, blue or grey crescent shape made of lipid (fatty) deposits that curves around the outer edge of the cornea
-tendon xanthomas - slowly enlarging subcutaneous nodules usually found attahced to the Achilles tendon/tendon over knuckles
-homozygous also have planal digital and natal cleft, cutanous xanthomas, Aortic stenosis
what is Niacin an example of
Nicotinic acid
what is the effect of Niacin
- liver = decrease VLDL synthesis + decrease VLDL & LDL levels
- Adipose = decrease sensitive lipase activity, decreased Triglycerides levels
- Decrease catabolic rate of HDL - increases HDL
- Increase clearance of VLDL by activating lipoprotein lipase
what are the indications for niacin
Hypercholesterolaemia
Hypertriglycidemia with low level of HDL
what are the adverse effect of the nicotinic acid
Cutaneous flushing
-Pruirtus & palpiattion
-dose dependant nausea + abdominal discomfort
- moderate incraese of liver enzymes to severe hepatoxicity
-hyperuricemia in 20% of patients
what decreases the adverse effects of Niacin
pretreatment with aspirin + NSAIDs
how does ezetimibe work ?
-Inhibits intestinal absorption of cholesterol by interfering with Neimann-Pick C1-Like 1 (NPC1L1) transport protein
-Decreases LDL and VLDL
hows does Colestipol/Cholestyramine work and how is it administered
-Binds bile acid (BA) in gut, prevents reabsorption, diverting hepatic cholesterol to BA synthesis, upregulates LDL receptors
-increasing LDL removal from the blood
-orally as they stay in the GIT
what are the adverse effects of Ezetimibe
diarrohoea, abdominal pain, headache (mild), rash, angioedema
what are the adverse effects of Colestipol/Cholestyramine
constipation, bloating, malabsorption of Vitamin K/folic acid/ascorbic acid
- disrupts absorption of digitalis, thiazides, warfarin and iron
what are Colestipol/Cholestyramine’s clinical uses
-primary hypercholesterolemia, when statins are contraindicated
-pruitus associated with bilarily obstruction
-bile acid diarrhoea
who cant take ezetimibe
breastfeeding mothers
which other lipid lowering drug is used with ezetimibe to treat hyperlipideamia
statins
ezetimbe is metabolised into an active metabolites - true or false
true
what is an example of a fibrate and what is the mechanism of action
Fenofibrate
-agonist at peroxisome proliferator-activated receptor (PPAR-a) nuclear receptor that regulate lipid metabolism
how does fibrates effects lipid metabolism
-increase synthesis of lipoprotein lipase by adipose tissue
-stimulates fatty acid oxidation in liver
-increase expression of apoA-1 & apoA5
-increase hepatic LDL uptake
=Marked reduction circulating VLDL and TG
Modest reduction in LDL
what are the adverse effects of fibrates
Common = Rash, GI disturbance
Rhabdomyolysis = smooth muscle degradation which causes renal failure by effecting glomerulus filtering
Clofibrate may cause gall stones
what are the clinical uses of fibrates
hypertriglyceridemia
mixed hyperlipidaemia
what types of patient cant take fibrates
-Allergies
-Diabetes
-people with Gall bladder, liver and kidneys conditions
give an example of statins
atorvastatin (long acting), lovastatin (short acting)
what is the mechanism of action for statins
-decrease synthesis of cholesterol (HMG CoA Reductase inhibitors)
-increase uptake of LDL (secondary) by increases LDL receptor synthesis which incraeses clearance of LDL by the liver
what is the cellular effect of statins
Endothelial function improves
Improved vascularisation of ischaemic tissue
Atherosclerotic plaque stabilisation
Reduces vascular inflammatory response
Reduced platelet activation
Enhanced fibrinolysis
Antithrombotic
what are the adverse effects of statins
normally well tolerated
may have muscle pain, GI disturbance, insomnia, rash
Rarely myositis and angiodema
when is statins not suitable
it patients have severe liver disease
when are statins used (3)
-primary hyperlipidaemia
-secondary hypercholesteroleamia
-secondary prevention of MI and Stroke
