disease characterized by the accumulation of fatty substances on the inne rwall of large & medium sized arteries (aorta, coronary, cerebra & renal)

if allowed to progress, atherosclerosis may eventually lead to CAD, cerebral vascular disease, peripheral vascular disease 

caused by other diseases and contributing factors:

two main lipids found in the blood (lipoproteins)

cholesterol & triglycerides

homeostatsis

lipoprotein particles are responsible for the transport of cholesterol and triglycerides in the blood stream

since each lipoprotein contains a diferent ratio of lipid to protein, each has a different _____ 

Classes of Lipoproteins:

Chylomicrons 

rich in TGs, low in cholesterol

serve to transport lipids from the GI to the liver 

Classes of lipoproteins:

VLDL 

Classes of lipoproteins:

LDL 

formed from VLDLs that have donated TGs and fatty acids to the tissues

rich in cholesterol - loosely bound and can be deposited in vascular spaces 

Classes of lipoproteins:

HDL 

scavenge cholesterol in the periphery and return it to the liver

BEST b/c the deactivate cholesterol 

every 1% reduction in cholesterol results in a __% reduction in CHD risk

for every 1 mg/dl decrease in HDL, there is a __% increased in CHD 

2%

2-3% 

What is the desirable level for total cholesterol?

what is the optimal level for LDL cholesterol? For diabetics?

What are the lowest healthy levels of HDL cholesterol for men and women? 

200 mg/dL

<100 mg/dL ; <70 mg/dL

<40 mg/dL is too low for men; <50 mg/dL is too low for women 

Which cholesterol is the primary target of therapy?

what is the first step in treatment? 

LDL cholesterol

risk assessment 

Major risk factors (exclusive of LDL cholesterol) that modify LDL goals:

(5) 

cigarette smoking

hypertension (BP >= 140/90 or on hypertensive meds)

low HDL cholestertol (<40)

family history of premature CHD (CHD in male first degree relative <55yrs; CHD in female first degree relative <65yrs)

age (men >45yrs; women >55yrs) 

Pharmacological interventions for lipid disorders:

(4) 

bile acid sequestrants - resins

statins (cholesterol synthesis inhibitors)

fibric acid derivatives

nicotinic acid - niacin 

can be used in pts w/ active liver disease (b/c not metabolized by liver)

can be used in children & in pregnancy

modestly lower LDL (15-30%); no effect on HDL; may increase triglycerides 

complete biliary obstruction

pts hypersensitive to these products

in pts w/ h/o constipation or bowel obstruction 

constipation, fecal impaction, bloating, flatulence

nausea, pruritus

vit A,D,E,K deficiency w/ long-term use (b/c these are  lipid soluble)

prolonged PT (prothrombin time) - b/c vit K is necessary to form these clots 

may decrease the absorption of other meds given concomitantly; especially fat soluble (b/c product will become bound w/ resin and excreted)

i.e. birth control pills

so, don't take the other meds for 2-4 hrs either way 

take before meals (30 min)

mix fiber powder into 4-8 oz of water, juice, milk, or carbonated beverages to improve taste

inhibit HMG-CoA which is required for the synthesis of cholesterol

reduc hepatic cholesterol synthesis reults in compensatory uptake of LDLs

SO, THESE ACT MORE ON ENDOGENOUS CHOLESTEROL 

modest reduction of elevated TG (10-30%)

decrease LDL (50%)

modest increase HDL (5-12%)

so, drug of choice for LDL, but not so much for the others 

inactive liver disease

pregnancy (b/c block huge amt of cholesterol nec. for membrane development)

pts w/ h/o liver disease % ETOH abuse

children & adolescents (b/c developing steroid hormones) 

well tolerated

expected GI discomfort

myopathy: muscle pain, inflammation, rhabdomyolosis (inflammation of general musculature in system; rare but deadly) 

an increase in CPK signals rhabdomyolosis 

coumadin/other anticoagulants: increase PT time

other lipid  lowering agents: rhabdomyolysis possible 

mech. of action is not well understood

believed that fibric acid derivatives increase the activity of lipoprotein lipase, a plasma enzyme that degrades chylomicrons & VLDL

verry effective for hypertriglyceridemia in which VLDL predominates

usually used as add on drugs to other agents

no effect on LDL 

reduces triglycerides by 50%

increases HDL very modestly 

high = <150

deadly = 500; at this point they are immediately life threatening, so a high triglyeride level is more important than high LDL, which is life threatening after years 

pts w/ h/o renal or liver disease, gallstones, or hypersensitivity to these agents

pregnancy & lactation 

GI problems (not major)

Cholelithiasis: gallstones; esp. in pts w/ a h/o gallstones (so, chart R abdominal pain and tell pt. to seek help when symptoms occur)

rash/eczema 

potentiate the effects of anticoagulant drugs

when used in cobo w/ statins, the risk of rhabdomyolysis usually outweighs the benefits 

reduces plasma VLDL by inhibiting VLDL synthesis in liver

reduces LDL by 15-25%

increases HDL by 25-30% 

reduces triglycerides by 50% 

flushing, itching, burning sensation common due to prostaglandin release (histamine); diminshed by aspirin (ASA) 30 min before dosing 

hyperglycemia

GI problems

only drug in the class

approved for use by itself or together w/ statins in pts w/ high cholesterol to reduce LDL cholesterol and total cholesterol

mechanism: selectively blocks intestinal absorption of exogenic cholesterol; localizes & appears to act at the brush border of the small intestine; inhibits the absorption of cholesterol, leading to a decrease in the delivery of intestinal cholesterol to the liver

as an add-on: increases HDL (4%), decreases LDL (30% when used w/ a statin), decreases TGs (11%)