Hyperlipidemia Flashcards
What is the major carrier of cholesterol in circulation?
LDL-C, contains 75% of total cholesterol, most atherogenic
_____ protects against development of atherosclerosis & removes free cholesterol from periphery & transports it back to liver for removal.
HDL-C
What carries cholesterol & triglycerides made in liver to sites of utilization?
VLDL-C
_____ are synthesized in intestines from dietary fat, are comprised of mostly triglycerides & transport dietary cholesterol & triglycerides?
Chilomicrons
Steps of pt evaluation for cholesterol screening (5)
- Determine lipoprotein level
- Determine presence of ASCVD (Atherosclerotic Caridovascular Disease)
- If no ASCVD, identify presence of ASCVD risk equivalents
- If no ASCVD or ASCVD risks, calculate 10 yr ASCVD risk factors
- If no ASCVD, ASCVD risks & 10 yr risk is >7.5, determine major ASCVD risk factors
Non-fasting lipoprotein panel should only evaluate the _____ and _____.
Total cholesterol & HDL-C
A fasting cholesterol evaluation is recommended if total cholesterol is _____ or _____
> 200mg/dL or HDL-C <40mg/dL
What is fasting defined as?
No oral intake for 8 hrs
In pts w/ ACS a lipoprotein sample should be obtained w/i _____ hrs.
24 hrs
LDL-C will be falsely _____ after 24 hrs for up to 4-6 weeks in pts w/ ACS
Low
How often, in all pts, should a fasting lipoprotein panel be checked?
Once every 5 years
What diseases indicate presence of ASCVD?
Coronary heart dz (ACS, hx of MI/UA/SA/PCI/CABG)
Cerebrovascular dz (stroke/TIA/>50% carotid occlusion) PAD
What are the ASCVD risk equivalents?
DM 1 or 2
What are the components of ASCVD risk calculation?
- Gender
- Age
- Race
- Total cholesterol
- HDL-C
- Systolic BP +/- treatment
- DM
- Smoking status
What are the ASCVD risk factors?
- LDL-C >160
- evidence of genetic hyperlipidemias
- Family hx of premature ASCVD: <55y in 1st degree male relative; <65y in 1st degree female relative
- CRP >2mg/L
- Coronary artery Ca score >300 or 75%ile for age, sex, ethnicity
- Elevated lifetime risk of ASCVD
nicotinic acid (Niacin) MOA
High doses inhibit lipolysis in adipose tissue. Fatty acids from adipose tissue are precursors to VLDL synthesis in liver which are then converted to LDL cholesterol.
Lipid effects of Niacin
LDL decreased by 5-25%
HDL decreased by 15-35%
TG decreased by 20-50%
nicotinic acid (Niacin) dosing/admin
IR: 250mg 1-3x/day w/ food, titrate every 4-7 days to 1-2g 2 or 3 times/day
ER: (Niaspan) 500mg QD @ bedtime, titrate by 500mg @ 4 wk intervals to max dose of 2g/day
ER combo (Advicor = niacin + lovastatin) 500/20, 750/20, 1000/20, 1000/40mg
nicotinic acid contraindications
- Liver dz
- Elevated LFTs
- GB dz
- Hypotension
- DM (uncontrolled)
- Active PUD
- Hyperuricemia
nicotinic acid adverse effects
- Derm: flushing/tingling/rash - tx w/ aspirin or NSAID
- GI: diarrhea, dyspepsia, N/V - tx w/ antacids
- Endocrine: incr fasting glucose or decreased glucose tolerance - adjust insulin/oral hypoglycemic agent
- Hepatic: elevated LFTs, hepatitis, hepatic failure (esp. in SR form) - repeat LFTs & d/c if 2-3x normal
- Rheum: gout
nicotinic acid monitoring
LFTs: baseline then every 12 wks for a year, then periodically
Glucose: baseline, after stable dosage established or increased & if symptomatic
Uric acid: baseline, in 4-6 wks and if joint pain develops
Bile acid sequestrant MOA
Binds bile salt in intestine preventing absorption, stimulating hepatic conversion of cholesterol to bile acids. This decreases intracellular conc of cholesterol which increases hepatic uptake of cholesterol by an increase in LDL receptors leading to decreased serum LDL & total cholesterol levels
Bile acid sequestrant lipoprotein effects
LDL decrease by 15-30%
HDL decrese by 3-5%
TG no change or increased
colestipol (Colestid) dosing/admin
Bile acid sequestrant
1g tablet/suspension/5g packet/scoop
2-16g/day QD/BID
Titrate @ 1-2 mo interval
cholestyramine (Questran)
4g cholestyramine/9g resin
4-24g/day (1-6 packets/scoops)
colesevelam (WelChol)
625mg PO tab
1.875g (3 tabs) BID or 3.75mg (6 tabs) QD
Max effect in 2 wks
Bile acid sequestrant contraindications
- familial dysbetalipoprotemia
- TG >400mg/dL absolute; >200mg/dL relative
- biliary obstruction
- hypersensitivity to bile acid sequestrants
Bile acid sequestrant adverse effects
GI: constipation, abd discomfort, epigast fullness, belching, flatulence - tx w/ incr fluid, fiber, stool softeners
Endocrine: incr TG
Heme: bleeding - tx w/ vitamin K
Bile acid sequestrant monitoring
LFT anually
Fibric acid derivatives MOA
Stimulate lipoprotein lipase activity thus hydrolyzing TG in chylomicrons & VLDL and hastening their removal from plasma
Fibric acid derivative lipoprotein effects
LDL decreased by 5-20%
HDL decreased by 10-20%
TG decreased by 20-50%
gemfibrozil (Lopid) dosing/admin
Fibric acid derivative
600mg PO BID 30 mins before meals
fenofibrate (Tricor)
67-200mg PO QD
clofibrate (Atromid-S)
2000mg/day in 2-4 divide doses
Fibric acid derivative contraindications
- Hepatic dysfunction
- Elevated LFTs
- Primary biliary cirrhosis or preexisting cholelithiasis
- Renal dysfunction (SCr>2.0mg/dL)
Fibric acid derivative adverse effects
GI: diarrhea, dyspepsia, N/V, RUQ pain, cholelithiasis
Heme: anemia, leukopenia, thrombocytopenia
Hepatic: LFTs - d/c if >3x NL
Musculoskeletal: myopathy - measure CK, d/c if elevated
SIADH (clofibrate)
Fibric acid derivative drug interactions - anticoagulants
Monitor and adjust anticoagulant dose. Gemfibrozil may enhance pharmacologic effect
Fibric acid derivative drug interactions - HMG-CoA reductase inhibitors
Increased risk of myopathy and rhabdo after 3 wks of lovastatin & gemfibrozil (decrease the max dose of statins used)
Fibric acid derivative monitoring
LFT @ baseline + every 6 mo for a year then anually
CPK @ baseline 4-6 wks, 3 mo, every 6 mo
CBC @ baseline, in 3-6 mo then yearly
HMG co-reductase inhibitor MOA
Inhibits enzyme HMG co-reductase (rate limiting step in cholesterol synthesis). Decreases intracellular cholesterol & causes the cell to increase # of LDL receptors.
HMG-CoA reudctase inhib lipoprotein effects
LDL decrease by 18-55%
HDL decrease by 5-15%
TG decrease by 7-30%
lovastatin (Mevacor) dosing/admin
HMG-CoA reductase inhib
Decreases LDL by 24-40%
20mg/d w/ evening meal, titrate to 80mg/d QD/BID
10mg initail dose in immunosuppressed or if using gemfibrozil or niacin concomitantly. Don’t exceed 20mg
Dont exceed 20mg/d in pts w/ severe renal insufficiency (CrCl<30ml/min)
pravastatin (Pravachol)
HMG-CoA reductase inhibitor
Decreases lipids by 22-34%
10-20mg/d @ bedtime or with evening meal, titrate to max of 40mg/d
10mg/d initial dose in pts w/ significant renal or hepatic dysfunction
simvastatin (Zocor)
HMG-CoA reductase inhib
24-40% lipid reduction
5-20mg/d, max 80mg/d; @ bedtime (qHS)
atrovastatin (Lipitor)
10-80mg QD
41-61% lipid reduction
rosuvastatin (Crestor)
5-10mg QD
45-63% lipid reduction
HMG-CoA reductase inhib contraindications
- Hypersensitivity
- Liver dz
- Elevated LFTs
HMG-CoA reductase monitoring
LFT @ baseline, 4-6 wks, 8-12 wks, 6 mo & 1 year after initiation/dose increase + every 6 mo after 1 year
CPK @ baseline, 4-6 wks, 3 months & if symptomatic of myopathy
HMG-CoA adverse effects
GI: constipation, diarrhea, dyspepsia, flatulence, nausea, abd pain
Hepatic: elevated LFTS - d/c if LFTs 3x norm
Musculoskeletal: myopathy - measure CK & d/c if CK elevated
Nuero: HA, dizziness
Atorvastatin, Lovastatin, Simvastatin drug interactions
3A4 Inhibitor: Cyclosporin Azole antifungals Macrolide abx Grapefruit juice Cimetidine Protease inhibitors Amiodarone Ca channel blockers
Fluvastatin
Rosuvastatin drug interactions
2C9 Inhibitor: Cimetidine Amiodarone TMP/SMX Omeprazole Fluconazole Fluvoxamine Ritonavir Zafirlukast
ezetimibe (Zetia) MOA
Decreased absorption of cholesterol from intestines by blocking the protein transport system that brings cholesterol into the intestinal cells.
What is different about the duration of action of ezetimibe (Zetia)?
Enterohepatic recycling of drug prolongs duration of action. Effective t1/2 = 28-30h
ezetimibe (Zetia) clinical efficacy
Flat dose response curve
10mg/day decreases LDL by 10% & increased HDL
Decreased triglycerides
Peak effect in 2 weeks
What is the benefit of adding ezetimibe (Zetia) to a statin?
Lowering of LDL by additional 15-20%
ezetimibe (Zetia) drug interactions
Fenofibrate, gemfibrozil increases ezetimibe levels by 50%
ezetimibe (Zetia) adverse effects
Chest pain Arthralgia Diarrhea Dizziness HA *no hepatotoxicity or skeletal muscle dysfunction
ezetimibe (Zetia) dosing admin
10mg BID w/ or w/o food
