Hyperlipidemia Drug DSA Flashcards
HMG-CoA reductase inhibitors
aka statins
fibric acid derivatives
aka fibrates
fenofibrate
gemfibrozil
bile acid sequestrants
aka resins
cholestyramine
colesevelam
colestipol
cholesterol absorption inhibitors
ezetimibe
common drug combo
simvastatin and ezetimibe
treatment for homozygous familial hypercholesterolemia
lomitapide
mipomersen
chylomicron
<.94g/mL
1-2proteins
80-95trig
VLDL
.94-1.006g/mL
6-10 proteins
55-80 trig
LDL
1.006-1.063g/mL
18-22 proteins
5-15 trig
HDL
1.063-1.21g/ml
45-55 proteins
5-10 trig
LPL
lipoprotein lipase
located on inner surface of capillary endothelial cells of mm and adipose tissue
primary hypertriglyceridemias
primary chylomicronemia
familial hypertriglyceridemia
familial combined hyperlipoproteinemia
familial dysbetalipoproteinemia
primary hypercholesterolemia
familial hypercholesterolemia
familial ligand-defective apoliproteinemia
familial combined hyperlipoproteinemia
Lp(a) hyperlipoproteinemia
other lipoprotein disorders
deficiency of cholesterol 7alpha-hydroxylase
autosomal recessive hypercholesterolemia
mutations in PCSK9 gene
HDL deficencies
HDL deficiencies
tangier disease
LCAT deficiency
familial hypoalphalipoproteinemia
secondary hyperlipoproteinemia
can be due to common to conditions or drugs such as DM, alcohol ingestion, estrogens, corticosterioids excess, hypopituitarism, acromegaly, resulting in hypertriglyceridemia
other causes of hypercholesterolemia
hypothyroidism
anorexia nevosa
early nephrosis
hypopituitarism
corticosteroid excess
CHD or CHD risk equivalents
LDL 100mg/dL
LDL at which lifestyle therapy should be initiated >100mg/dL
LDL level at which to consider drug therapy >130mg/dL
2+ risk factors
LDL < 130mg/dL
LDL level at which to initiate lifestyle therapy >130
drug therapy >130
drug therapy if risk <10% >160mg
0-1 risk factors
LDL <160
LDL at which to initiate lifestyle therapy >160
LDL at which to initiate drug therapy >190
CHD equivalents
symptomatic carotid a disease
peripheral arterial disease
abdominal aortic aneurysms
diabetes
total fat
20-25%
saturated fat
<8% of daily intake
cholesterol
<200mg/day
carbohydrates
50-60% of total calories
dietary fiber
20-30g/day
Statins
most effective agents in reducing LDL levels and best tolerated class of lipid lowering agents
stuctural analog of HMG-CoA
statin pharmacokinetics
extensive 1st pass metabolism
plasma half lives ranges from 1-3 hours w/exception of atrovastatin (14hrs) rosuvastatin (19hrs)
primarily excreted in bile
statins pharmacodynamics
inhibit MHG-CoA reductase, rate limiting enzyme in cholesterol synthesis
statin potency
rosuvastatin>atorvastatin>>simvastatin>pitavastatin=lovastatin=pravastatin>fluastatin
high intensity atorvastatin dosage
40-80mg
high intensity rousuvastatin dosage
20mg
statins and liver
elevations of serum aminotransferase activity
mm and statins
creatine kinase activity levels may increase, particularly in patients who have high level o fphysical activity
rhabdomyolysis can occur rarely leading to kidney injury
myopathy can occur w/monotherapy
statin drug interactions
increased risk of myopahty w/cyclosporine, itraconazole, erythromycin, gemfibrozil, or niacin
increases warfarin levels
should not be used w/inducers phenytoin, friseofulvin
statin contraindications
pregnancy, lactation, or likely to get pregnant
liver disease
skeletal m myopathy
statins in children
restricted to those w/homozygous familial hypercholesterolemia and some heterozygous
niacin
most effective agent for increasing HDL
lowers LDL and VLDL
only lipid lowering agent that significantly reduces Lp(a)
niacin chem and pharmacokinetics
converted to amide and incorporated into NAD
well absorbed distibuted to amily hepatic, renal, adipose tissue
extensive first pass
excreted in urine
Niacin pharmacodynamics
inhibits lipolysis of triglycerides in adipose tissue -> fewer circulating FFAs -> lower VLDL -> lower LDL
fibrinogen levels reduces and tissue plasminogen activaotr levels are increased which can reverse some of endothelial cell dysfunction
therapeutic uses of niacin
often used in combo w/biel acid sequesterant or reductase inhibitor for heterozygous familial hypercholesterolemia and some cases of nephrosis
mixed lipemia incompletely responsive to diet
adverse effects of niacin
most common side effect is an intense cutaenous flush (aspirin can mitigate this)
pruritis, rashes, dry skin or mucous membranes, acanthosis nigricans
may cuase hepatotoxicity
contraindications of niacin
hepatic disease or active peptic ulcer
DM -> increased insulin resistance -> elevated insulin -> acanthosis nigricans
fibrates pharmacokinetics
derivated of fibric acid
well absorbed when taken w/meal, highly bound to serum albumin
gemfibrozil half life = 1.5hrs
fenofibrate half life = 20 hrs
fibrates pharmacodynamics
acts as agonist ligands for PPARalpha (TF receptor)
when activated increases expression of genes for lipoprotein strucutre and function
VLDL levels decrease LDL levels modestly decrease, HDL increse modestly
uses of fibrates
hypertriglyceridemia where VLDL predominates
dysbetalipoproteinemia
hypertriclygeridemia due to viral protease inhibitors (HIV)
fibrate adverse effects
GI
lithiasis, especially gallstones
myositis, myopathy, rhabdomyolysis
fibrate drug interactions
fibrates potentiate actions of coumarin and indanedione anticoagulants
fibrates contraindications
hepatic or renal dysfunction
not sure in pregnancy or lactation
biliary tract disease or high risk for gallstones
bile acid sequesterants pharmacokinetics
insoluble in water
neither absorbed nor metabolically altered by intestine, totally excreted in feces
resin pharmacodynamics
positively bound substances that bind negatively charged bile salts
increased excretion of bile causes more cholesterol to be converted to bile
decline in hepatic cholesterol causes increase in LDLRs
resin uses
primary hypercholesterolemia
type IIa or IIb hyperlipidemias
relieve pruitus in patients w/bile salt accumulation
digitalis toxicity
adverse effects of resins
GI- constipation, nausea, flatulence)
at high does imprai absorption of fat soluble vitamins
drug interactions resins
impari absorption of
tetracycline
phenobarbital
digoxin
warfarin
pravastatin
flustatin
aspirin
thiazide diuretics
resin contraindications
diverticulits, preexisting bowel disese, cholestasis
cholesterol absorption inhibitors pharmacokinetics
highly water insoluble
enters enterohepatic circulation as active compound
excreted in feces 22 hour half life
cholesterol absorption pharmacodynamics
selectivly inhibits GI absorption of cholesterol and phytosterols
effective even in absence of dietary cholesterol b/c inhbits reabsorption of cholesterol excreted in bile
uses of cholesterol absorption inhibitors
various causes of elevated cholesterol
cholesterol absorption inhibitor contraindicatios
don’t combine w/resins b/c resins will inhibit ezetimibe absorption
lomitapide
directly binds to and inhibits microsomal triglyceride transfer protein which is located in lumen of ER -> prevents assembly of apo-B containing lipoproteins -> decrease LDL
lomitapide adverse effects
GI, increased liver aminotransferase levels, and hepatic fat accumulation
costs >250,000/yr
mipomersen
antisense oligonucleotide targets apoB-100 mRNA and disrupts fnx
mipomersen adverse effects
injection site rxns, flu like symptoms, headache, elevation of liver enzymes, expensive
