Lipid lowering drugs + Atherosclerosis Flashcards
what is atherosclerosis
thickening of the inner arterial wall: fatty materials (plaque) chronic inflammation reduced blood flow increased blood pressure
medical conditions associated with atherosclerosis
- coronary artery disease
- stroke
- peripheral vascular disease (narrowing of b.v > reduced blood flow to limbs)
relationship between blood cholesterol level and heart attack risk
increase in blood cholesterol level increases heart attack risk
how are lipids transported through the bloodstream
in lipoprotein complexes
where is most blood cholesterol found
LDL fraction
what ratio of cholesterol is beneficial
high HDL: LDL
plaque formation
- absorption of oxidized LDL-C - endothelial surface injury
- inflammatory response
- macrophage infiltration
- foam cell formation
- plaque enlarges - capped by sm cells
- cap ruptures:
- RBC platelets are attracted
- clots form
- potential thrombosis
hyperlipidemia
high levels of lipids in blood
primary (genetic):
elevated LDL, VLDL, or chylomicrons
type II: highest risk for atherosclerosis
risk factors for secondary hyperlipidemia
alcohol smoking obesity diabetes mellitus kidney disease hypothyroidism hypertension liver disease retinoic acid age
drugs used to treat atherosclerosis
STATINS
FIBRATES
Cholesterol absorption inhibitors:
- BILE ACID-BINDING RESINS
- EZETIMIBE
NIACIN
OMEGA-3 FATTY ACIDS
what is STATIN
HMG CoA reductase inhibitor (block enzyme needed to make cholesterol)
Prodrug: administered in inactive form - metabolized to active form
mimics the HMG CoA substrate intermediate
how does STATIN work
plasma LDL reduction
HMG CoA reductase inhibitor
direct cholesterol synthesis reduction
increased expression of LDL receptors
reduce vascular inflammation
reduce platelet aggregation
stabilisation of atherosclerotic plaques
immunosuppression
side effects of STATIN
GI disturbance
myositis (muscle inflammation)
myopathy (muscle weakness)
how does FIBRIN work
clofibrate
- activates PPARa - regulator of lipid metabolism in blood
activation promotes fatty acid degradation - promotes increased lipoprotein lipase activity
- triglyceride degradation
- reduces serum VLDL - promotes decreased diacetyl acetyltransferase activity
- DAT = triglyceride formation - increased LDL uptake
- increased plasma HDL
side effects of FIBRATES
GI distress
rhabdomyolysis when given with a statin
interferes with metabolism of oral anticoagulants by competing for Cytochrome P450 drug-metabolizing enzymes
Cholesterol absorption inhibitors I:
BILE ACID BINDING RESINS
treat: hypercholesterolemia
-anion exchange resins, exchange Cl- for bile acids
= decrease bile acid + cholesterol reabsorption
increase LDL receptors
reduce plasma cholesterol + coronary heart disease
side effects of BILE ACID RESIN
constipation
inhibits absorption of fat-soluble vitamins
should not be administered with medications that are primarily absorbed in the intestines
Cholesterol absorption inhibitors II:
EZETIMIBE
competitive inhibitor of cholesterol absorption from intestine
- blocks binding of cholesterol to transporter
- moderate effect on LDL levels when used alone
-used in combination with low dose statin - benefit reduced tolerance to statins
Side effects: GI distress
NIACIN
treats hypercholesterolemia
most effective - when used with bile binding resins
stimulates GPR109A = inhibit fat breakdown in adipose tissue
=decreases VLDL formation => increasing HDL fraction
side effects of nicotinic acid
worsen cardiac arrhythmias
worsen gout/gall bladder/liver disease
GI distress
flushing/rash
reduced with extended-release niacin
OMEGA-3 FATTY ACIDS
found in oily fish
reduce plasma triglycerides by increasing lipoprotein lipase + reducing synthesis of VLDL
eicosapentaenoic acid can replace arachnoid acid in cell membranes - decreased synthesis of prostaglandins (involved in platelet aggregation/inflammation)
not useful for treating high cholesterol // may elevateHDL fraction
ACETYLSALICYLIC ACID
inhibits platelet aggregation by blocking Cox-1
CLOPIDOGREL
anti-platelet
