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96 Cards in this Set

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Epidemiologic Data/Two major early studies showed:
Framingham
MRFIT
*Continuous/Linear relationship between cholesterol levels and CHD
*Risk of CHD increases as LDL increases
*Risk of CHD increases at low levels of HDL
Framingham Heart Study
1948; 5,127 men & women; 30-62 years; Total C>240 increases risk of CHD; elevated HDL-C protects against CHD; elevated LDL increases risk of CHD; total-C: HDL-C RATIO predictor of CHD risk
MRFIT
12,866 middle-aged men with CHD risk factors; 1% decrease in total-C=2% decrease in CHD risk
Key Classes of Lipid-Lowering Drugs
1. HMG-CoA reductase inhibitors (statins)
2. Fibric Acid Derivatives (fibrates)
3. Nicotinic Acid (niacin)
4. Bile acid sequestrants (resins)
Which most effective?
Statins
HMG-CoA Reductase Inhibitors (STATINS) MOA
MOA: 1)Upregulate LDL receptors in liver/"pulls out the LDL"
2)Inhibit the biosynthesis of LDL
Statins: contraindications and warnings
Contraindications: Active liver disease, hypersensitivity, pregnancy/lactation
Warnings: Muscle-related effects; abnorm liver function tests
*Dosing
*Maximum response in __ wks
*Administer in evening except for PLC
*Four
PLC
Not taken in the evening/take anytime: Pravachol, Lipitor, Crestor
Fibric Acid Derivatives (fibrates)
MOA: breakdsdown the VLDL/IDL, which REDUCES TGs
Safety: GI adverse events
Nicotinic Acid (Niacin)
-Increases HDL
-Limited use due to poor tolerability: 25% discontinue
-Flushing of face
Bile Acid Sequestrants (Resins)
Bind to intestinal bile acids and form insoluable; Safety: GI disturbances; hard to tolerate; POWDERS/MIXES/tablets; "Welcol"
Selective Cholesterol Inhibitors
Inhibits absorbption of cholesterol in SMALL INTESTINE; "zetia"
Dosing: once daily w or w/o statin
Safety: back pain; diarrhea
NCEP ATP III Guidelines
1) LDL primary target of therapy
2) Most stringent classification of LDL/HDL/TG Levels
3) Recom intensive treatment for patients w/ CHD but focus is prevention of CHD
FOCUS of NCEP
1) LDL 2) TG
NCEP ATP III stands for...
National Cholesterol Education Program Adult Treatment Panel
HDL
Reverse Cholesterol Transport
Low HDL=high CHD risk
>60 HDL=carioprotective
Risk Equivalents
Diabetes
Atherosclerosis rel diseases
Multiple risk factors: 10-yr CHD risk >20%
What type of cholesterol do most diabetics have?
LDL: small, dense, bullet-like C that can penetrate the endothelial
Risk Factors (excluding LDL)
^Smoking
^Hypertension
^Low HDL
^Family history
^Age: men 45, women 55
Risk Categories
CHD/CHD risk equivalents: 10-yr CHD risk: >20%; <100
Multiple >=2 risk factors: 10-yr CHD risk <=20%; <130
0-1 risk factor: 10-yr CHD risk: <10%; LDL<160
Risk Determination: If pt has greater than ___ risk factors assess 10-year absolute risk
TWO
What is the goal of primary prevention?
Goal: reduce both long-term and short-term risk for CHD in people who have yet to have a cardiovascular event
What is the goal of secondary prevention?
To prevent another event with Patients who have established CHD or CHD risk factors, for example diabetes
True or False: The Primary goal of lipid-lowering therapy: to lower LDL-C and the secondary goal is to increase HDL
Secondary Goal is to decrease TG (or non-HDL cholesterol)
True or False: Pravachol is indicated for both Primary prevention of coronary events & Secondary prevention of cardiovascular events
TRUE
What are some of the drug interactions associated with Zocor?
Drug interactions:
Other potent CYP3A4 inhibitors (eg, cyclosporine, ketoconazole, clarithromycin, grapefruit juice)
Lipid-lowering drugs (fibrates, niacin), amiodarone, verapamil, propranolol, digoxin, anticoagulants
What is Zetia's MOA?
Inhibits intestinal absorption of cholesterol
Vytorin should be taken in the evening with or without food. True or False.
True
What are Lipitor's indications?
In the prevention of CV disease: Reduce risk of MI
Reduce risk for revascularization + angina
Reduce Stroke
Reduce elevated total cholesterol, LDL-C, apo B, triglycerides; increase HDL-C in primary hypercholesterolemia and mixed dyslipidemia
NCEP ATP III stands for...
National Cholesterol Education Program Adult Treatment Panel
HDL
Reverse Cholesterol Transport
Low HDL=high CHD risk
>60 HDL=carioprotective
Risk Equivalents
Diabetes
Atherosclerosis rel diseases
Multiple risk factors: 10-yr CHD risk >20%
What type of cholesterol do most diabetics have?
LDL: small, dense, bullet-like C that can penetrate the endothelial
Risk Factors (excluding LDL)
^Smoking
^Hypertension
^Low HDL
^Family history
^Age: men 45, women 55
Risk Categories
CHD/CHD risk equivalents: 10-yr CHD risk: >20%; <100
Multiple >=2 risk factors: 10-yr CHD risk <=20%; <130
0-1 risk factor: 10-yr CHD risk: <10%; LDL<160
Risk Determination: If pt has greater than ___ risk factors assess 10-year absolute risk
TWO
What is the goal of primary prevention?
Goal: reduce both long-term and short-term risk for CHD in people who have yet to have a cardiovascular event
What is the goal of secondary prevention?
To prevent another event with Patients who have established CHD or CHD risk factors, for example diabetes
True or False: The Primary goal of lipid-lowering therapy: to lower LDL-C and the secondary goal is to increase HDL
Secondary Goal is to decrease TG (or non-HDL cholesterol)
True or False: Pravachol is indicated for both Primary prevention of coronary events & Secondary prevention of cardiovascular events
TRUE
What are some of the drug interactions associated with Zocor?
Drug interactions:
Other potent CYP3A4 inhibitors (eg, cyclosporine, ketoconazole, clarithromycin, grapefruit juice)
Lipid-lowering drugs (fibrates, niacin), amiodarone, verapamil, propranolol, digoxin, anticoagulants
What is Zetia's MOA?
Inhibits intestinal absorption of cholesterol
Vytorin should be taken in the evening with or without food. True or False.
True
What are Lipitor's indications?
In the prevention of CV disease: Reduce risk of MI
Reduce risk for revascularization + angina
Reduce Stroke
Reduce elevated total cholesterol, LDL-C, apo B, triglycerides; increase HDL-C in primary hypercholesterolemia and mixed dyslipidemia
Lipitor Dosing
10 mg, 20 mg, 40 mg, 80 mg tablets
Flexible Start™
Starting dose: 10 mg/day or 20 mg daily
Dose range: 10 mg to 80 mg
Patients requiring larger LDL-C reduction (>45%) may start on 40 mg/day
80 mg dose is a titration dose
Taken any time of day, with/without food
What is the reduction of LDL-C for Lipitor across the 10-80 mg dose range?
39-60% over the 10-80 mg
What is the reduction of TG for Lipitor across the 10-80 mg dose range?
19-37%
How many patients were tested in ASCOT-LLA?
10,305 hypertensive subjects aged 40 to 79 years with at least 3 other
Results of ASCOT-LLA
36% reduction in nonfatal MI/CHD
45% reduction in nonfatal MI
27% in fatal/nonfatal stroke
29% reduction in total coronary events
21% reduction in total CV events, (incl revasc procedures)
CARDS results...
37% in major coronary events
48% in stroke
27% in total mortality
Which of the following statins can be taken once-daily, with or without meals, at any time during the day?
Pravachol, Lipitor, Crestor
Lipid hypothesis
Elevated total – C and LDL – C are central to the pathogenesis of Coronary heart disease and that lipid lowering reduces CHD risk.
Secondary prevention
A Secondary prevention study seeks to determine whether intervention (usually drug therapy) can prevent established disease from progressing (MI, angina, PVD, CAD)
First US study to show that CHD events are related to elevated lipids and lipoproteins
Framingham
Was MRFIT an epidemiologic or a secondary prevention study?
Epidemiologic study that followed 12,866 middle-aged men with CHD risk factors.
Continuous, linear relation between Total C and CHD mortatlity was noted
1% drop in TC = 2% drop in CHD risk
Match the trial with its drug:
4S
WOSCOPS
CARE
AFCAPS/TexCAPS
LIPID
ASCOT
4S - Zocor
WOSCOPS – Pravachol
CARE – Pravachol
AFCAPS/TexCAPS – Mevacor
LIPID - Pravachol
AVERT – Lipitor
Describe 4S
Secondary
4,444 patients
Simvastatin/Zocor
Drug to treat high TG
Fibric Acid Derivatives
Examples:
Gemfibrozil
Fenofibrate
True or false: The combination of statins with fibrates or niacin should generally be avoided.
TRUE
Lipitor does which of the following in patients with hypercholesterolemia?:
A. lowers total cholesterol
B. lowers LDL cholesterol
C. lowers apo B
D. all of the above
D. All of the above
What is Lipitor’s effect on HDL?
Raises it by 5-9%
Where is Lipitor metabolized?
In the Liver: CYP 450
When a patient is initiated on Lipitor, what is the protocol for liver function testing?
Baseline
12 weeks
Semi-annually (upon titration, need to run again after 12 weeks)
Which drugs increase the risk of myopathy/ rhabdomyolysis with concomitant statin use:
Fibrates
Niacin
Erythromycin/macrolides (not Zithromax)
Azole antifungals
cyclosporine
The following describes which drug class?
Inconvenient dosing
High incidence of GI effects
LDL reductions of 15 – 30%
HDL increases of 3 – 5%
Bile Acid Sequestrants
How often do you need to complete a fasting lipoprotein trial?
From the age of 20 – every 5 years (unless health status dictates more frequently)
At what triglyceride level is treatment considered necessary, secondary to LDL?
>200
In clinical trials, what % of patients on Lipitor discontinued therapy because of adverse events?
<2%
Flexible Start
10mg, 20mg, or for patients requiring >45% drop in LDL to reach goal…40mg may be used as a starting dosage.
What is the clinically significant ALT elevation (where you would discontinue a statin or any other med)?
Clinically significant level is >3xULN
10 mg rate is 0.2
20 mg rate is 0.2
40 mg rate is 0.6
80 mg rate is 2.3
Which type of lipoprotein contains the highest concentration of cholesterol?
LDL: small, bullet-like, very dense, able to easily penetrate endothelial
In ASCOT, Lipitor 10 mg reduced the risk of nonfatal MI and Fatal CHD by _______.
36%
What impact would an HDL level of 68 have on a person’s CHD risk factor profile?
Decrease it by ONE factor (Cardioprotective)
TRUE or FALSE: Nonpharmacologic therapy is the essential first step in the management of CHD?
TRUE!
What is the LDL cholesterol target level for drug therapy in a patient with CHD or Diabetes?
<100
What is the LDL reduction of Zetia monotherapy?
18%
The target LDL Cholesterol Goal is < 160 mg/dl for a patient with ≥____ risk factors and no CHD.
2
What is the generic name for Crestor?
Rosuvastatin
Follow-up of MRFIT showed that a __% reduction in total cholesterol resulted in __% reduction in CHD risk
1%; 2%
What type of trial was WOSCOPS?
PRIMARY
Which trials are secondary prevention trials for Zocor and Pravachol?
4S, CARE
The 40mg dose of this statin is not available for rapid distribution to pharmacies and is reserved for those patients who are not effectively treated with the 20mg dose.
Crestor
As of today, which statin is indicated for both primary and secondary prevention?
Pravachol
True or False: Zocor is indicated to reduce both elevated LDL and triglycerides.
True
With regards to the NCEP III Guidelines and TGs, what is considered to be normal?
<150
What is the most common side effect reported with Lipitor?
GI
Explain an epidemiologic study
Is Observational; no intervention by investigators. Is used to determine whether intervention can prevent disease development (primary prevention)
Is used to determine whether intervention can prevent established disease from progressing.
(secondary prevention)
Hypertriglyceridemia Treatment
Decrease weight and increase physical activity in BORDERLINE HIGH, HIGH and VERY HIGH patients; add drug therapy (statin) for HIGH patients; add very low-fat diet/fibrate/nicotinic acid for VERY HIGH pateients
Zocor Facts
Starting dose: 20-40 mg/day
Comes in: 5, 10, 20, 40, 80
Merck
"simvastatin"; GI; myopathy; rhabdomyolysis; grapefruit juice; lipid-lwring drugs; 3rd statin, best statin pre-Lipitor
Mevacor
"lovastatin"; Merck; 1987, first statin; 1/2-life=2-4 hours; 10, 20, 40 mg; start dose: 20mg/day with evening meal
Pravachol
"pravastatin sodium"; Bristol-Meyers Squibb; 1/2-life=77 hours; 10, 20, 40, 80 mg; start dose: 40, max 80; can be admin anytime with/w/o food; treats PRIMARY/SECONDARY
Lescol
"fluvastatin sodium"; Novartis; 20, 40 mg or 80 mg XL; start dose of 20-80mg; food decreases rate of absorption; secondary; liver complications
Crestor
Treats primary, high TG; homozygous FH; liver issues; myopathy, rhabdomyolysis; proteinuria/blood in urine/Asian patients
Zetia
Liver issues; pregnancy catagory C; GI; 10mg dosing; Merck-Sharing Plough
Vytorin
"simvastatin/ezetimibe"; Merck Schering-Plough; zetia 10 + Zocor 10, 20, 40 or 80; once daily 10/20 or 10/40; taken at night, with/w/o food; works in liver; "takes care of food you eat"; myopathy; rhabdomyolysis, grapefruit juice