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125 Cards in this Set
- Front
- Back
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T/F:
Hypercholesteremia, decrease in LDL and HDL are linked to increase in CHD, stroke and death |
False
Hypercholesteremia, INCREASED LDL, decreased HDL are linked to increase in CHD, stroke and death |
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T/F:
Initial therapy for lipid disorders is usually TLC. |
True, diet and exercise
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How are pharmalogical agents choosen for hyperlipidemia?
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Depends on what lipid abnormalities are present and how severe they are
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___TC, ____ LDL, _____ HDL, reduce mortality/CHD events
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_decrease_TC, _decrease_ LDL, _increase_ HDL, reduce mortality/CHD events
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What is hyperlipidemia?
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Elevated blood levels of lipoproteins (cholesterol, triglycerides, and phospholipids)
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Lipoprotein abnormalities include >/= one of the following?
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elevated TC
elevated LDL elevated TG reduced HDL |
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What are some nonlipid CHD risk factors added to hypercholesteremia? (5)
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Smoking, HTN, DM, low HDL, Electrocardiographic abnormalities
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What is the artheroschlerosis timeline?
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Foam cells-->fatty cells--> intermediate lesions--> artheroma--> fibrous plaque--> complicated lesion/rupture
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What can contribute to atheroschlerosis (general)?
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Lifestyle and genetics
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What is essential for cell membrane formation and hormone synthesis?
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Cholesterol
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T/F:
Lipids are present in free form and circulate in the plasma |
False,
not present in free forms, circulate in plasma as lipoproteins |
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What are the 3 major plasma lipoproteins?
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VLDL- 10-15% of Scholesterol
LDL- 60-70% of Schol (includes IDL) HDL- 20-30% of Schol |
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T/F:
Elevated cholesterol is not necessarily familial hypercholesteremia (type IIa) |
True
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What are the elevation of lipoproteins for the 6 types of hyperlipoproteinemia classifications?
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Type I- chylomicrons
Type IIa- LDL Type IIb- LDL+VLDL Type III- IDL Type IV- VLDL Type V- VLDL + chylomicron |
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What are some 2ndary causing of hypercholesteremia that are disease related?
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Hypothyroidism
Obstructive liver disease Nephrotic syndrome Anorexia nervosa Acute intermittent porphyria |
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What are some drugs that cause 2ndary hypercholesteremia?
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progestins
thiazides glucocorticoids BB isotretinoin protease inhibitors cyclosporine mirtazipine sirolimus |
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What are some disease states that cause 2ndary hyperTRIGLYCERIDEMIA?
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obesity
DM lipodystrophy ileal bypass surgery sepsis pregnancy acute hepatitis systemic lupus erythematous monocolonial gammopathy: multiple myeloma, lymphoma |
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What are some medications that cause 2ndary hyperTRIGLYceridemia?
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alcohol
estrogens isotretinoin BB glucocorticoids bile acid resins thiazides asparaginase interferons azole antifungals mirtazipine anabolic steriods sirolimus |
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What are some 2ndary causes of HYPOcholesteremia?
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malnutrition
malabsorption myeloproliferatibe disease chronic infectious disease (AIDS and TB) monoclonal gammopathy Chronic live disease |
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What are some 2ndary causes of low HDL?
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Malnutrition
obesity medications such as: non ISA BB anabolic steriods isotretoin progestins |
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Metabolic syndrome is considered 3 or more of the following?
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abdominal obesity:
F- >35 in M- >40 in elevated TG (>150mg/dl) increased BP (>130/85) elevated glucose (>100) HDL: F- <50 M- <40 Proinflammatory state |
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What are the symptoms of hyperlipidemia? (9)
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None
severe CP, palpitations sweating anxiety SOB loss of conciousness speech or movement difficulty abdominal pain sudden death |
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What are th signs of hyperlipidemia? (7)
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None
pancreatitis eruptive xanthomas peripheral polyneuropathy HTN BMI > 30 kg/m2 waist size >40 in men >35 in women |
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Lab test in pts w hyperlipidemia will usually show an elevation in what? While showing a decrease in?
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Increase:
TC, LDL, TG, apolipoprotein B, C-reactive protein Decrease: HDL |
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If a pt doesnt fast before a lipid panel which measurements are reliable?
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Only TC and HDL
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When should a fasting lipid panel be done?
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Every 5 yr for adults > 20 years
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What are the classifications for Total Cholesterol?
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<200 desirable
200-239 borderline high 240 high |
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What are the classifications for LDL?
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<100 optimal
100-129 near or above optimal 130-159 borderline high 160-189 high 190 very high |
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What are the classifications for HDL?
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<40 low
60 high |
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What are the classifications for TG?
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<150 normal
150-199 borderline high 200-499 high 500 very high |
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What are the major risk factors that modify LDL goals? (5)
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Age (M>45 F>55)
Family Hx of premature CHD (1st degree M<55 F<65) Smoking HTN >140/90 or on HTN meds Low HDL <40 M <50 F If HDL>60 subtract 1 risk factor |
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What are th CHD/CHD equivalents?
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Other atherschlerotic diseases such as PVD, adominal aortic aneurysm, symptomatic carotid artery disease
DM CHD>20% in 10 yr risk score |
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Framingham risk score is based on what factors? (5)
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Age
TC Smoking status HDL SBP |
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T/F:
LDL predicts morbidity/mortality and is the primary treatment target |
True
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What are th LDL goals for those with a high risk category? When should drug therapy be considered?
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Goal: <100
TLC: >100 Drug: >100 |
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What are th LDL goals for those with a moderately high risk category? When should drug therapy be considered?
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Goal: <130
TLC: >130 Drug: >130 |
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What are th LDL goals for those with a moderate risk category? When should drug therapy be considered?
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Goal: <130
TLC: >130 Drug >160 |
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What are th LDL goals for those with a lower risk category? When should drug therapy be considered?
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Goal: <160
TLC: >160 Drug: >190, 160-189 optional |
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Who might be a good candidate for goal LDL <70?
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People with IHD/CAD and
initial or recurrect ACS DM Smokers diffuse vascular disease Metabolic syndrome |
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What are some mitigating circumstances against agressive Tx?
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$$$
CrCl<30 ml/min Age >80 Small body frame/frailty Life expectancy <2 yrs instability critical DI 40% reduction and close to goal |
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What is the cornerstone of tx for lipid management?
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TLC
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What are some TLC that can be made in pts w hyperlipidemia?
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Low saturated fat and cholesterol diet
Increase soluble fiber in diet Weight reduction Increase physical activity if inactive (30min/day most of week) Smoking cessation TLC should never replace drug tx |
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What are the calculated allowed fat intake in pts?
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9 kcal/g fat
15-35% calories as fat <7% of cal as sat fat 2000 cal diet: 56-78 g of total fat <16 g of sat fat |
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What are the decreases in LDL in pt w LDL=160 when complying to TLC?
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Low sat fat/cholesterol: -12
Vicous fiber(10-25g/d): -8 Plant stanols/sterols(2g/d): -16 Total: -36mg/dL |
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How long should you wait to for a follow up after initiating TLC in a pt? What if its controlled?
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6 weeks, then every 4-6 months
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What is the lipid lowering effect of bile acid resins?
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LDL 15-20%
HDL 3-5% TG no change or increased |
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What is the lipid lowering effect of niacin?
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LDL 5-25%
HDL 15-35% TG 20-50% |
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What is the lipid lowering effect of statins?
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See excel chart
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What is the lipid lowering effect of fibrates?
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LDL: slight increase to 20% decrease
HDL: 10-20% TG: 20-50% |
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What is the lipid lowering effect of ezetimibe?
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LDL: 18-25%
HDL: 1-5% TG: 5-14% |
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When are bile acid resins NOT a 1st line tx?
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When TG are elevated at baseline, hypertriglyceridemia may worsen w BAR monothreapy
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What are the choices for tx in class I (chylomicron elevation)?
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Not indicated
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What are the choices for tx in class IIa (LDL elevated)?
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Statins
Cholestyramine or colestipol Niacin |
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What are the choices for tx in class IIb (LDL and VLDL elevated)?
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Statins
Fibrates Niacin |
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What are the choices for tx in class III (IDL elevated)?
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Fibrates
Niacin |
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What are the choices for tx in class IV (VLDL elevated)?
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Fibrates
Niacin |
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What are the choices for tx in class V (VLDL and chylomicrons elevated)?
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Fibrates
Niacin |
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What do you do if the LDL reduction isnt 30-40% by the 2nd visit?
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Consider high statin dose or add 2nd agent
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What is the drug of choice for hyperlipidemia (high LDL)?
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Statins! Unless pregnant or nursing, then contraindication!!!!!
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What is the MOA of statins?
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Reduce hepatic cholesterol synthesis--> lowering intracellular cholesterol--> stimulates upregulation of LDL receptors and increases the uptake of nonHDL particles from systemic circulation
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Statins are what class of drug?
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HMG-CoA reductase inhibitors
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When should statins be taken?Which are the exceptions?
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In the evening when hepatic cholesterol production is peaked
Excepetion: atrovastatin and rosuvastatin can be taken at any time of the day |
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Which statin requires dosage adjustments in severe renal impairment and hepatic disease?
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Rosuvastatin
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What are the ADR of statins that occurs in a few % of pts?
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Elevated serum transaminases
Myalgia Myopathy RHABDOMYOLYSIS (break down of muscle fibers) flu like symptoms mild GI disturbances |
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What are the potential time course effects of statins?
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LDL lowering--> endothelial fxn restored--> inflammation reduced--> ischemic episodes reduced--> vulnerable plaque stabilized--> cardiac events reduced
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What statins are used in primary preventative tx?
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Pravastatin
Atorvastatin Lovastatin (PAL) |
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What statins are used in secondary preventative tx (Had CHD/CHD equivalent event)?
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Simvastatin
Pravastatin |
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Are all statins and doses created equally?
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No
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Are statins safe in non-alcoholic steatohepatitis/FLD, chronic liver failure, and compensated cirrhosis?
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Yes
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What are statins contraindicated in?
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Uncompensated cirrhosis
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What should be monitored in pt that are SYMPTOMATIC of myopathy or rhabdomyolysis? What should be done in regards to the statin?
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CK (creatine kinase)
Statin should be reduced in dose or d/c depending on pt |
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What risk factors are found with elevated CK?
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Female
Age Renal insufficiency Biliary obstructive liver disease Hypothyroidism Trauma Seizures Falls Rigorous exercise Infection |
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What are some exacerbating factors associated with elevated CK?
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GFJ
Concomitant meds Herbals |
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When d/c a statin due to PN or cognitive impairment what are some factors that could be contributing?
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DM
RI alcohol abuse B12 deficiency cancer hypothyroidism AIDS lyme disease heavy metal intoxication |
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What is the MOA of BAR?
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Inhibits the reabsorption of bile bile acids decreasing LDL
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What are the BARs and the dosings?
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Cholestyramine: 4-16g/d
Colestipol: 5-20g/d Colesevelam: 625 mg tabs 6-7 tabs/d |
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What are the ADRs for BARs? (4)
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Constipation
bloating ab pain flatulence but... no systemic toxicity |
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What are some drug interactions of cholestyramine and colestipol (BARs)?
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Bind other negatively charged drugs
Impede absorption of drugs and/or fat soluble vitamins |
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What is the rule of thumb when giving BARs with other drugs?
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Must give other drug 1 hour before or 4-6 hours after giving BAR
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What is the safest lipid lowering drug?
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BAR
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What can BARs aggrevate?
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Hypertriglyceridemia
caution if TG >200 Contraindicated if TG >400 |
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What can powdered BARs be mixed with?
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liquids or foods such as OJ, oatmeal, or applesauce
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T/F:
Colestipol is odorless and tasteless |
True
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What is the MOA of ezetimibe?
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Selectively inhibits cholesterol absorption
This decreases the delivery of cholesterol to the liver increasing the expression of LDL receptors thus decreasing the cholesterol content of atherogenic particles |
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What limits the systemic exposure of ezetimibe?
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Ezetimibe and its active glucuronide metabolite circulate enterohepatically
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What are the DI with ezetimibe?
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Statins: none
Cholestyramine: decreases AUC of ezetimibe, should be admin. >2 hrs prior or >4 hrs after BAR Fibrates: not recommended Cyclosporin: can increase ezetimibe levels No sign. interactions with: antacids, cimetidine, warfarin, digoxin, estradiol, levonorgestral, glipizide, or tolbutamide |
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What is the indication for ezetimibe as monotherapy or combo with statins?
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Hypercholesteremia (IIa)
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What are the contraindications of ezetimibe?
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Hypersensitivity (rash)
Moderate to sever liver enzyme elevation Pregnancy |
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When statins and BAS are used in combo there is no benefit in _____ in high TG
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When statins and BAS are used in combo there is no benefit in _HDL_ in high TG
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When is a statin/niacin combo desirable?
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Pt w abnormal HDL and/or TG when statins dont work alone
Same with statin/fibrate |
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What is the increased risk w a statin/niacin combo?
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Heptatoxicity and myopathy
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T/F:
The risk of myopathy is greater in a statin/niacin combo then in a statin/fibrate combo |
False
statin/fibrate combo has a higher risk for myopathy |
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For pt with a TG >500 why should control of TG take primary focus?
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Reduce risk of abdominal pain and pancreatitis
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Whats the equation for nonHDL?
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nonHDL= TC- HDL
Approx. LDL + VLDL |
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With the tx of mixed hyperlipidemia what are the goals?
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1. acheive LDL
2. acheive non HDL |
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What are the examples of fibrates given in the lecture?
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Fenofibrate, gemfibrozil, clofibrate
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What is MOA of fibrates?
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Decrease TG and increase clearance of VLDL/ reduced production
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T/F:
Fibrates can cause a concurrent increase in LDL |
True
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What is the increase in HDL in fibrates?
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>10-15%
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What does the efficacy of fibrates depend on?
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Lipoprotein type and baseline TG
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What is the dosing for gemfibrozil?
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BID 30 min before meals
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T/F:
Fenofibrate is the preferred fibrate because it can be given w/o regards to food |
True
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What are fibrates contraindicated in?
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Renal failure
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Combination with these drugs can cause an increase risk of muscle toxicity
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what is statins or niacin
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What are some ADRs of fibrates?
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GI complaint, rash, myalgia, HA, fatigue
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What can clofibrate cause?
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Gallstones
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Fibrates have what type of effect in pts on sulfonylureas?
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Enhanced hypoglycemia
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Fibrates can also potentiate the effect of what class of drugs?
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Anticogulants,
monitor PT/INR closely |
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Fibrates are ___ effective then niacin and ____ tolerated
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Fibrates are _less_ effective then niacin and _better_ tolerated
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Diets rich in omega 3 FA from oily fish can do what to lipids?
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Decrease:
TC, TG, LDL, CV events Increase: HDL |
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What is the Rx for fish oil and how is it given?
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Lovaza 4TPOQD
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How does Lovaza effect lipids?
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lowers TG 14-30%
raises HDL 10% |
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What is a potential complication of high doses of Lovaza?
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Thrombocytopenia, bleeding disorders
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How much EPA & DHA is recommended for high TG?
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2-4g/d decreases TG by 45%
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What are some ADR of omega3FA?
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GI, fishy aftertaste, increased risk of bleeding/thrombocytopenia, worsen glycemic control
increased LDL abnormal LFT |
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How much EPA & DHA is found in most omega3FA supplements?
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EPA: 180mg
DHA: 120mg enough for prevention but not enough to lower TG |
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What are factors that contribute to low HDL?
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Smoking, obesity, insulin resistance, male, high carbo diet
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What is the MOA of nicotinic acid (niacin)?
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Decrease of hepatic production of VLDL and apolipoprotein B
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What is the best agent to raise HDL?
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Niacin
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What products are available containing nicotinic acid?
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Immediate release: 2-4g/d
Extended release: 1-2g/d OTC sustained release: <2g/d |
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What are the ADR of niacin?
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FLUSHING, itching, HA (immediate release)
Heptatoxicity, GI (sustained release) Activation of peptic ulcers Hyperglycemia and reduced insulin sensitivity |
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What are the contraindications for niacin?
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Active liver disease or high LFT
PUD |
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For Niacin ER what is the daily dosing for each week?
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Week 1-4: 500mgQD
Week 5-8: 1000mgQD Titrate: 1500mgQD Titrate: 2000mgQD |
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What can be taken to reduced flushing from niacin?
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Taking ASA at bedtime and/or eating low fat snack at bedtime (applesauce)
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Niacin should be used with caution in which pts?
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Those w DM, gout, hyperuricemia, PUD
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