Dyslipidemia Flashcards
2 major sequelea of lipoproteins?
acute pancreatitis
athersclerois (leading cause of death in U.S. men and women)
Types of Lipoproteins
apolioprotein/apoprotein
chylomicrons
VLDL
IDL
LDL
HDL
LP(a)
what do know about chylomicrons?
Fat > muscles, fat cells, liver
the largest lipoprotein
least dense
triglyceride is digested and cholesterol remains.
Cholesterol > liver for metabolism
HIGHEST TRIGLYCERIDE CONTENT
What to know about VLDL?
protein, fat, cholesterol
synthesized in the liver
5 different lipoproteins > removal of apoprotein and esterification of cholesterol > IDL and LDL
2nd highest in triglyercerides
what to know about LDL?
chiefly cholesterol
only apoprotein it is associated with is apoB-100
what to know about HDL?
highest protein/lipid ratio so most dense
“good cholesterol”
carries cholesterol away from tissues to the liver
increased levels decrease risk of CV diesease
what things increase HDL levels?
exercise
^ estrogen
alcohol
weight loss
smoking cigarettes
how long to fast before blood draw for lipid levels?
10 hours
total cholesterol level
<200
LDL level?
<130
HDL level in men?
> 40
HDL level in women?
> 50
triglyceride levels?
<120
how do you differentiate the lipoprotein disorders?
by the lipoproteins involved
two kinds of primary lipoprotein disorder?
primary hypertryglerideemia
primary hypercholesterolemia
Diseases in primary hypertryglercerideemia?
primary chylomicronemia
familial hypertryglereridemia
severe
moderate
FAMILILIAL COMBINED HYPERLIPOPROTEINEMIA
familial dysbetalipoproteinemia
diseases in primary hypercholesterolemia?
familial hypercholesterolemia
familial ligand deffective apolioprotein B-100
FAMILIAL COMBINED HYPERLIPOPROTEINEMIA
LP(a) hyperlipoproteinemia
2 main things with secondary lipoprotein disordres?
must consider 2ndary causes before primary disorders can be diagnosed
lipoprotein abnormality usually resolves if underlying disorder can be treated
lipoprotein disorder treatment
dietary measures first
if CAD & PVD start pharmacologic therapy simultaneously.
in which lipoprotein disorders is drug therapy always required?
familial hypercholesterolemia
familial hyperlipoproteinemia
how long must weight be stabilized for diet to be sufficient control of lipoprotein disorders?
1 month
what three things increase LDL?
cholesterol
saturated fat
trans fat
what three things raise triglycerides?
^ total fat
alcohol
excess calories
what two things increase VLDL?
sucrose
fructose
what route are all statins?
PO
Statins are most effective for lowering what?
LDL
what do statins do beside lower LDL?
decrease oxidative stress
decrease vascular inflammation
^stability of atherosclerotic lesion
when are statins started immediately?
post ACS regardless of lipid levels
Are statins used for mono or combo therapy?
both
which was the fist statin?
Lovastatin (mevacor)
which statin is the most lipophilic?
atorvastatin (lipitor)
which statin is the least lipophilic? (most lipophobic)
rouvastatin (crestor)
what percentage of statin medications are absorbed?
ranges from 45-75%
which two statins are inactive lactone pro drugs which are hydrolyzed in the GI tract?
lovastatin and simvistatin
what is the half life of lovastatin and simvistatin?
1-3hr
which two statins are flourine containing congeners which are active as given?
atrovastatin and rouvastatin
all statins are given at night except for?
atorvastatin and rouvastatin
how are statins metabolised?
liver enzymes CPY34A and CYP2C9
how are statins excreted?
mostly in bile, but 5-20% in urine
food increases the absorption of all statins except for?
pravastatin
Toxicity of statins
^serum aminotransferase activity
elevated CK
drug interactions with CYP inducers/inhibitors
myopathy
when do do you need to DC statins?
serious injury, trauma, or major surgery
or
precipitous drop in LDL levels
how much can serum aminotransferase activity increase in statin toxicty?
up to 3x normal levels
in elevated aminotransferase activity from statin toxicity when can you still continue therapy?
when the patient is asymptomatic
what are symptoms of increased aminotransferase activity from statin toxicity?
malasie, anorexia, precipitous drop in LDL (DC immediately)
Other names for Niacin?
nicotinic Acid or Vit B3
what does Niacin do?
decrease: LDL, VLDL, LP(a)
^ HDL
when medication is the most effective in ^ HDL and also the only agent that can decrease LP (a)?
Niacin
what happens to Niacin in the body?
converted to an amide builder for NAD
how is Niacin secreted>
unmodifed in urine or as several metabolites
Niacin MOA?
inhibit VLDL secretion into the blood
decrease production of LDL
^ hepatic clearance of HDL > decreased triglycerides
is Niacin used for mono or combo therapy?
both
When to use Niacin?
hypercholesterolemia
severe mixed lipemia incompletely responsive to diet
dysbetalipoproteinemia
hypertriglyeridemia
toxicity of niacin?
Acanothis Nigricans
Insulin resistance
Atrial arrhythmias
Cutaneous vasodilation
“Eye” Macular edema
Nausea & and pain
Name two Fibric Acid derivatives
gemfibrozil (lopid)
fenofibrate (tricar)
is gemfibrozil (lopid) protein bound?
yes
how does food affect absorption of gemfibrozil (lopid)?
increases its absorption
does gemfibrozil (lopid) cross the placenta?
yes
gemfibrozil (lopid) half life?
1.5 hours
how is gemfibrozil (lopid) eliminated?
70% kidney elimination
Describe fenofibrate (tricar)
isopropyl ester that is hydrolyzed in the intestine
half life of fenofibrate (tricar)?
20hrs
how is fenofibrate (tricar) eliminated?
60% in urine
25% feces
MOA of fibric acid derivatives?
ligand for nuclear transcription receptor PPAR-alpha
physiologic effects of fibric acid derivatives?
^oxidation of fatty acids in liver and striated muscle
^lipolysis of lipoprotein triglycerides
decrase VLDL
modest reduction in LDL
mod ^ of HDL secretion
when are fibric acid derivatives used?
VLDL predominated hypertriglyceridemia
dysbetalipoproteinemia
toxicty of firbric acid derivatives?
potentiate actions of coumadin and indanedione anticoagulants
^ mypopathy risk with statins
^ risk of cholesterol gall stones (especially women, obese, native americans)
when to avoid fibric acid derivatives?
hepatic and renal dysfunction
where does bile acid come from?
metabolite of cholesterol
name some bile acid binding resins
colestipol
cholestyramine
colesevelam
when are bile acid binding resins used?
isolated ^ LDL only
if triglyerides ^ > ^ VLDL
how do Resins work?
bind bile acids in the intestines >
prevent reabsorption > 10x ^ of excretion
how often are resins administered?
BID or TID with meals
which medication class is helpful to decrease pruritis from cholestasis & bile salt accumulation?
bile acid binding resins
toxicity of resins
impairs absorption of other meds (give 1 hr before meal or 2hrs after)
Constipation/bloating so CI in diverticulitis
malabsorption of Vit K, monitor PT in patients taking anticoagulants
Name an intestinal sterol absorption inhibitor
Ezitimibe
MOA of ezitimibe
selective inhibition of absorption of cholesterol and phytosterols
which transport protein does ezitimibe target?
NPC1L1
how does ezitimibe effect lipid levels?
decrase LDL
minimal ^ HDL
half life of ezitimibe
22hrs
ezitimibe is synergystic with what medications?
statins
toxicity of ezitimibe?
low incidence of reversible hepatic dysfunction
