Management of Hyperlipidemia Flashcards
1
Q
What are the 3 types of lipids?
A
(1) Cholesterol
(2) Triglycerides
(3) Phospholipids
2
Q
Cholesterol
- A ________, primary component of cell _______
- Precursor for _____ acids which are required for _____ absorption
- Precursor for ______ steroids (aldosterone, others)
- Precursor of _____ hormones (estrogens, androgens)
- 40 - 60% of cholesterol is _________, the rest comes from diet
A
- A STEROID, primary component of cell MEMBRANES
- Precursor for BILE acids which are required for FAT absorption
- Precursor for ADRENAL steroids (aldosterone, others)
- Precursor of SEX hormones (estrogens, androgens)
- 40 - 60% of cholesterol is ENDOGENOUS, the rest comes from diet
3
Q
Triglycerides
- Composed of 3 _________ esterified to a single molecule
- Free fatty acids are used as ______ sources
- Triglycerides in the body are provided by ______ fats and _______ conversion of carbohydrates
A
- Composed of 3 FATTY ACIDS esterified to a single molecule
- Free fatty acids are used as ENERGY sources
- Triglycerides in the body are provided by DIETARY fats and HEPATIC conversion of carbohydrates
4
Q
Phospholipids
- Lipid containing __________ acid residues in addition to fatty acids and ______
- Major component of cell ________
- Play a role in single __________ in nerve tissue
A
- Lipid containing PHOSPHORIC acid residues in addition to fatty acids and ALCOHOL
- Major component of cell MEMBRANES
- Play a role in single TRANSDUCTION in nerve tissue
5
Q
Lipoproteins
- Cholesterol and triglycerides are _____phobic — cannot be transported through polar substance (i.e. ________) alone
- Lipoproteins are globular particles of high molecular weight that are…
- used to transport ______ lipids t/o the body
- Composed of a _______ lipid core consisting of triglycerides and cholesterol esters surrounding by a _______ surface of phospholipids, free cholesterol and apoproteins
A
- Cholesterol and triglycerides are HYDROPHOBIC — cannot be transported through polar substance (i.e. BLOOD) alone
- Lipoproteins are globular particles of high molecular weight that are…
- used to transport NON-POLAR lipids t/o the body
- Composed of a NON-POLAR lipid core consisting of triglycerides and cholesterol esters surrounding by a POLAR surface of phospholipids, free cholesterol and apoproteins
6
Q
What are the 6 types of lipoproteins?
A
(1) Chylomicrons
(2) Very low density lipoproteins (VLDL)
(3) Intermediate Density Lipoproteins (IDL)
(4) Low Density Lipoproteins (LDL)
(5) High Density Lipoproteins (HDL)
(6) Apolipoproteins
7
Q
Chylomicrons
- Formed in ________, transport dietary fat to ________ cells and ________
- Composition = > 90% _________, 2% ___________
- Role in disease: taken up by cells of the _______ wall, utilizing macrophages /c the end result of generation of ______ cells
A
- Formed in INTESTINE, transport dietary fat to PERIPHERAL cells and LIVER
- Composition = > 90% TRIGLYCERIDES, 2% CHOLESTEROL
- Role in disease: taken up by cells of the VESSEL wall, utilizing macrophages /c the end result of generation of FOAM cells
8
Q
Very Low Density Lipoproteins (VLDL)
- Transport endogenous cholesterol from _______ to _______
- Composition: 60 - 70% ________; 12% __________
- Role in disease: Uncertain. There is an ________ relationship btw TG rich lipoprotein concentrations (VLDL and IDL) and HDL
- it is thought that atherogenicity is more a function of low ______ as opposed to high _______
A
- Transport endogenous cholesterol from LIVER to PERIPHERY
- Composition: 60 - 70% TRIGLYCERIDES; 12% CHOLESTEROL
- Role in disease: Uncertain. There is an INVERSE relationship btw TG rich lipoprotein concentrations (VLDL and IDL) and HDL
- it is thought that atherogenicity is more a function of low HDL as opposed to high VLDL
9
Q
Intermediate Density Lipoproteins (IDL)
- Intermediate product of hydrolysis of ______ by lipases
- Composition: Cholesterol esters and __________
- Not though tot be contributory to _________
A
- Intermediate product of hydrolysis of VLDL by lipases
- Composition: Cholesterol esters and TRIGLYCERIDES
- Not though tot be contributory to DISEASE
10
Q
Low Density Lipoproteins (LDL)
- Generated from further “_________” of IDL
- Composition: _____ cholesterol content, ______ triglycerides (accounts for _____% of cholesterol in blood)
- Role in Disease: major class of lipoproteins attributable to _________ disease
A
- Generated from further “DELIPIDIZATION” of IDL
- Composition: HIGH cholesterol content, LOW triglycerides (accounts for 60 - 70% of cholesterol in blood)
- Role in Disease: major class of lipoproteins attributable to ATHEROSCLEROTIC disease
11
Q
High Density Lipoproteins (HDL)
- ________ cholesterol form the peripheral tissue for transport back to the liver for conversion into ______
- Composition: 45% _________, 25% ____________, 25% ____________
Role in disease: _____________ (removes ________ from foam cells in atherosclerotic lesions)
- Often referred to as “______ cholesterol” –> the ________ the better
A
- REMOVES cholesterol form the peripheral tissue for transport back to the liver for conversion into BILE
- Composition: 45% PROTEIN, 25% PHOSPHOLIPIDS, 25% CHOLESTEROL
Role in disease: PROTECTIVE (removes CHOLESTEROL from foam cells in atherosclerotic lesions) - Often referred to as “GOOD cholesterol” –> the HIGHER the better
12
Q
Apolipoproteins
- Provide __________ stability to lipoproteins and serve as ________ for enzymes
- Role in Disease: apolipoprotein is a ________ like protein that is thought to increase risk of __________ heart disease
A
- Provide STRUCTURAL stability to lipoproteins and serve as CO-FACTORS for enzymes
- Role in Disease: apolipoprotein is a PLASMINOGEN like protein that is thought to increase risk of CORONARY heart disease
13
Q
- High level of oxidized LDL cholesterol –> _______ formation in the walls of arteries –> atherosclerosis
- HDL cholesterol is able to _________ cholesterol from the atheroma
- Atherogenic cholesterol —> _______, _______, ______
A
- High level of oxidized LDL cholesterol –> ATHEROMA formation in the walls of arteries –> atherosclerosis
- HDL cholesterol is able to REMOVE cholesterol from the atheroma
- Atherogenic cholesterol —> LDL, VLDL, IDL
14
Q
Causes of Hyperlipidemia
- Diet
- Hereditary
- Hypothyrodism
- Anorexia
- Obesity
- Diabetes _________
- Pregnancy
- ____________ liver disease
- Acute ________
- _________ syndrome
- Systemic lupus ____________
- __________ inhibitors
- Atypical _________
A
- Diet
- Hereditary
- Hypothyrodism
- Anorexia
- Obesity
- Diabetes MELLITUS
- Pregnancy
- OBSTRUCTUIVE liver disease
- Acute HEPATITIS
- NEPHROTIC syndrome
- Systemic lupus ERYTHEMATOUSUS
- PROTEASE inhibitors
- Atypical ANTIPSYCHOTICS
15
Q
2014 NLA Guideline Summary
- Places patients into risk categories based upon various factors such as: ASCVD, ASCVD risk factors, Diabetes, Baseline LDL-C
- Provides target lipoprotein goals based upon risk categories
- Low/mod/high:
A
- Places patients into risk categories based upon various factors such as: ASCVD, ASCVD risk factors, Diabetes, Baseline LDL-C
- Provides target lipoprotein goals based upon risk categories
- Low/mod/high: <130 non-HDL-C; < 100 LDL-C; < 90 Apo B
- Very high: <100 non-HDL-C; < 70 LDL-C; < 80 Apo B
16
Q
Lifestyle Modifications
- Heart healthy _______
- Regular ________
- ________ cessation
- Maintenance of a healthy __________
A
- Heart healthy DIET
- Regular EXERCISE
- SMOKING cessation
- Maintenance of a healthy WEIGHT
17
Q
What are the 4 Dietary Sources of Cholesterol?
A
(1) Monounsaturated
(2) Polyunsaturated
(3) Saturated
(4) Trans
18
Q
What source of cholesterol comes from…
- Olives, olive oil, canola oil, peanut oil, cashews, almonds, peanuts and most other nuts; avocados
A
Monounsaturated
19
Q
What source of cholesterol comes from…
- corn, soybean, safflower and cottonseed oil; fish
A
Polyunsaturated
20
Q
What source of cholesterol comes from…
- Whole milk, butter, cheese, and ice cream; red meat; chocolate; coconuts, coconut milk, coconut oil, egg yolks, chicken skin
A
Saturated
21
Q
What source of cholesterol comes from…
- most margarines; vegetable shortening; partially hydrogenated vegetable oil; deep-fried chips; many fast foods; most commercial baked goods
A
Trans
22
Q
Effects of Monounsaturated Cholesterol
- Lowers ______
- Raises _______
A
- Lowers LDL
- Raises HDL
23
Q
Effects of Polyunsaturated Cholesterol
- Lowers ______
- Raises ______
A
- Lowers LDL
- Raises HDL
24
Q
Effects of Saturated Cholesterol
- Raises both _____ and ______
A
- Raises both LDL and HDL
25
Effects of Trans Cholesterol
| - Raises ______
- Raises LDL
26
Clinical ASCVD Statin Benefit Group
- High-intensity statin if age less than or equal to _____ y.o.
- Moderate-intensity statin if age greater than or equal to _____ y.o. or not candidate for high-intensity
- High-intensity statin if age less than or equal to 75 y.o.
- Moderate-intensity statin if age greater than or equal to 75 y.o. or not candidate for high-intensity
27
LDL-C (greater than or equal to 190 mg/dL) Statin Benefit Group
- ______ intensity statin
- HIGH intensity statin
28
Diabetes (type 1 or 2, age 40 - 75 y.o.)
- _______ intensity statin
- High intensity statin if 10 year ASCVD risk greater than or equal to _____%
- MODERATE intensity statin
| - High intensity statin if 10 year ASCVD risk greater than or equal to 7.5%
29
Greater than of equal to 7.5% estimated 10 year ASCVD risk and age 40 - 75 year
- ________ to _______ intensity statin
- MODERATE to HIGH intensity statin
30
Statin — MOA
- inhibit enzyme responsible for converting HMG-CoA to ___________
- __________ step in the production of cholesterol
- inhibit enzyme responsible for converting HMG-CoA to MEVALONATE
- RATE-LIMITING step in the production of cholesterol
31
Statin — most common side effects
- m_________
- Elevated ________ enzymes
- Monitoring: Check ___________ and __________ at baseline and then only if clinically indicated
- MYOPATHY
- Elevated LIVER enzymes
- Monitoring: Check CREATINE KINASE and LIVER FUNCTION TESTS at baseline and then only if clinically indicated
32
Statin — rare side effects
- new onset of __________
- ___________ stroke
- new onset of DIABETES
| - HEMORRHAGIC stroke
33
Statin — Contraindications
- Active _______ disease, unexplained persistent elevations in _______
- ___________ / lactation
- Selection medications: more common /c ________/___________
- Active LIVER disease, unexplained persistent elevations in LFT's
- PREGNANCY / lactation
- Selection medications: more common /c LOVASTATIN/SIMVASTATIN
34
Statin — Drug Interaction
- Fibrates = increased risk of _________ and rhabdomyolysis
- Niacin = do not exceed dose of 1g/day d/t increased risk of _______ and rhabdomyolysis
- Fibrates = increased risk of MYOPATHY and rhabdomyolysis
| - Niacin = do not exceed dose of 1g/day d/t increased risk of MYOPATHY and rhabdomyolysis
35
Statin
- avoid unnecessary __________ of statins
- obtain h/o prior or current _______ symptoms to establish baseline before initiating statin therapy
- avoid unnecessary DISCONTINUATION of statins
| - obtain h/o prior or current MUSCLE symptoms to establish baseline before initiating statin therapy
36
Statin
- Unexplained severe _____ symptoms or _______
- promptly _________ statin and address possibility of ___________
- Urinalysis, ________ levels, and _________ levels
- Unexplained severe MUSCLE symptoms or FATIGUE
- promptly DISCONTINUE statin and address possibility of RHABDOMYOLYSIS
- Urinalysis, CK levels, and SERUM CREATININE levels
37
Statin — Mild to moderate symptoms
- Evaluate for other conditions that may increase risk of _______ symptoms
- Establish causal relationship between ______ symptoms and _____ therapy
If causal relationship...
- _________ original statin
- Resume _____ dose alternative statin
- Increase to maximum ________ dose
- Evaluate for other conditions that may increase risk of MUSCLE symptoms
- Establish causal relationship between MUSCLE symptoms and STATIN therapy
If causal relationship...
- DISCONTINUE original statin
- Resume LOW dose alternative statin
- Increase to maximum TOLERATED dose
38
Non-Statin Therapies
- Niacin
- Bile acid sequestrates (BAS)
- Ezetimibe
- PCSK9 inhibitors
- Fibric acids
- Omega 3 Fatty acids
Primarily for triglyceride management
- Fibric acids
- Omega 3 Fatty acids
39
Niacin
- ________ acid, vitamin ____
MOA:
- inhibits ____ synthesis and hepatic secretion
- inhibits release of ________ acids from adipose tissue
- NICOTINIC acid, vitamin B
MOA:
- inhibits VLDL synthesis and hepatic secretion
- inhibits release of FREE FATTY acids from adipose tissue
40
Niacin — Clinical Uses
- adjunctive therapy for lowering ______, can lower _________
- most effective agent at increasing _____
- adjunctive therapy for lowering LDL, can lower TRIGLYCERIDES
- most effective agent at increasing HDL
41
Niacin should NOT be used if
- Hepatic transaminase > _______ times ULN
- Severe _______ symptoms, persistent _________, acute ______, or unexplained _______ pain
- Hepatic transaminase > 2 - 3 times ULN
| - Severe CUTANEOUS symptoms, persistent HYPERGLYCEMIA, acute GOUT, or unexplained ABDOMINAL pain
42
Niacin
- may cause significant __________
- can premeditate /c ________, take at bedtime /c food, avoid _____ beverages, _____ foods, or _____ showers around administration time
- may cause significant FLUSHING
- can premeditate /c ASPIRIN, take at bedtime /c food, avoid HOT beverages, SPICY foods, or HOT showers around administration time
43
What are these products?
- Cholestyramine
- Colestipol
- Colesevelam
Bile Acid Sequestrants
44
Bile Acid Sequestrants — MOA
| - binds bile in GI tract for fecal ______ to stop _________ cycling
- binds bile in GI tract for fecal EXCRETION to stop ENTEROHEPATIC cycling
45
Bile Acid Sequestrants
| - __________ adverse effects may be limiting factor
- GASTROINTESTINAL adverse effects may be limiting factor
46
Bile Acid Sequestrants
- Avoid if baseline fasting triglycerides exceed ____ mg/dL
- Discontinue if triglycerides exceed ______ mg/dL on therapy
- Avoid if baseline fasting triglycerides exceed 300 mg/dL
| - Discontinue if triglycerides exceed 400 mg/dL on therapy
47
Bile Acid Sequestrants
| - cholestyramine / colestipol separate all drugs by __ hour before or __ hours after
- cholestyramine / colestipol separate all drugs by 1 hour before or 4 hours after
48
Ezetimibe (Zetia) — MOA
| - inhibits the absorption of intestinal _________
- inhibits the absorption of intestinal CHOLESTEROL
49
Ezetimibe (Zetia) — Efficacy
- ____ reduction of 18%
- reduced primary composite endpoint of _____________ death, non-fatal ______, UA /c hospitalization, coronary ________, and non-fatal stroke
- LDL reduction of 18%
- reduced primary composite endpoint of CARDIOVASCULAR death, non-fatal MYOCARDIAL INFARCTION, UA /c hospitalization, coronary REVASCULARIZATION, and non-fatal stroke
50
Ezetimibe (Zetia)
| - monitor _______ transaminases when clinically indicated. Discontinue if persistent levels > ____ times ULN
- monitor HEPATIC transaminases when clinically indicated. Discontinue if persistent levels > 3 times ULN
51
What are 3 adverse effects of Ezetimibe (Zetia)?
(1) Overall well tolerated
(2) Abdominal pain
(3) Diarrhea
52
PCSK9 Inhibitors
(1) Praluent (alirocumab) = subcutaneous injection every _____ weeks
(2) Repatha (evolucumab) = subcutaneous injection every ______ weeks
(1) Praluent (alirocumab) = subcutaneous injection every 2 weeks
(2) Repatha (evolucumab) = subcutaneous injection every 2-4 weeks
53
PCSK9 Inhibitors — MOA
- monoclonal antibody that inhibits a protein called PCSK9 --> increased expression of ______ receptors on hepatocyte surfaces --> increased _______ clearance from the liver
- monoclonal antibody that inhibits a protein called PCSK9 --> increased expression of LDL receptors on hepatocyte surfaces --> increased CHOLESTEROL clearance from the liver
54
PCSK9 Inhibitors — Efficacy
- Have been shown to lower ________ levels by 40 - 72%
- Outcome studies have shown reduced rates of ____________ and ______ death
- Have been shown to lower LDL-C levels by 40 - 72%
| - Outcome studies have shown reduced rates of MYOCARDIAL INFARCTION and CARDIOVASCULAR death
55
PCSK9 Inhibitors — Adverse Effect
- _______ site reactions
- _________ infections
- INJECTION site reactions
| - RESPIRATORY infections
56
Fibric Acids — MOA
- Inhibits ________ of VLDL and increases _________ of VLDL, fatty acid _____, and _________ of triglyceride-rich particles
- Inhibits SYNTHESIS of VLDL and increases CATABOLISM of VLDL, fatty acid OXIDATION, and ELIMINATION of triglyceride-rich particles
57
What type of drugs are these...
- Fenofibrate (Tricor, Triglie, Trillpix, Antara)
- Gemfibrozil (Lopid)
Fibric Acids
58
What are 4 contraindications to Fibric Acids?
(1) Pregnancy
(2) Severe hepatic disease
(3) Severe renal disease
(4) Gall bladder disease
59
What are 2 adverse drug reactions of Fibric Acids?
(1) gastrointestinal
| (2) myopathies /c gemfibrozil
60
Triglyceride Management
- Primary goal = prevent _________
- non-pharmacological therapy = weight _______, e_______, avoid large amounts of ________
- Primary treated /c _________ or _________ fatty acids
- Primary goal = prevent PANCREATITIS
- non-pharmacological therapy = weight LOSS, EXERCISE, avoid large amounts of ALCOHOL
- Primary treated /c FIBRATES or OMEGA-3 fatty acids
