Hyperlipidemia Drugs

Front 1

risk factors for coronary heart disease?

Back 1

age
gender
family history of premature CHD
current cigarette smoking
hypertension
low HDL
obesity

Front 2

age and gender limits for risk factor for CHD?

Back 2

male >45 yrs
female >55 yrs

Front 3

family history of CHD as risk factor for CHD?

Back 3

1st degree relative: male <55 yrs, female <65 yrs

Front 4

hypertension limits for consideration as risk factor for CHD?

Back 4

BP >130/85
use of HTN meds

Front 5

obesity numbers as risk factor for CHD?

Back 5

BMI >25
waist circumference >40 inches in men
waist circumference >35 inches in women

Front 6

metabolic syndrome?

Back 6

3/5 risk factors:
hypertension (>130/85 or meds)
low HDL (<40)
obesity (BMI >25)
hyperglycemia (fasting >110)
high TG (>150)

Front 7

possible secondary causes of hyperlipidemia?

Back 7

type II DM
hypothyroid
obstructive liver disease
chronic renal failure
drugs

Front 8

drugs that increase LDL and decrease HDL?

Back 8

progestins
anabolic steroids
corticosteroids

Front 9

distinct protein on chylomicrons?

Back 9

B-48

Front 10

which lipoprotein is B100 found on?

Back 10

VLDL
IDL
LDL

Front 11

cornerstone to correcting primary hyperlipidemias?

Back 11

diet adjustment

Front 12

bile acid sequestrants?

Back 12

cholestyramine
colestipol
colesevelam

Front 13

which bile acid sequestrant is more palatable due to its polymeric hydrophilic gel form rather than a positively charged anion exchange resin?

Back 13

colesevelam

Front 14

mechanism of bile acid sequestrants?

Back 14

act locally to bind bile acids and increase bile acid excretion;
decrease cholesterol absorption

Front 15

outcomes data with bile acid sequestrants?

Back 15

clinical trial evidence of primary and secondary CHD risk reduction

Front 16

adverse reactions with bile acid sequestrants?

Back 16

upper and lower GI side effects: bloating, gas, constipation;
more common with resins rather than colesevelam

Front 17

drug interactions of bile acid sequestrants?

Back 17

impaired absorption of warfarin, digoxin, vitamins ADEK

Front 18

how minimize drug interactions with bile acid sequestrants?

Back 18

take other meds 2-4 hrs before bile acid sequestrants

Front 19

effects of bile acid sequestrants?

Back 19

decreased LDL
slight increased HDL
increased TG

Front 20

contraindications for bile acid sequestrants?

Back 20

patients with high TG (>400)

Front 21

statins mechanism of action?

Back 21

competitive inhibitors of HMG CoA reductase --> decreased liver cholesterol synthesis --> increased liver LDL receptors --> increased LDL clearance

Front 22

least efficacious statin?

Back 22

fluvastatin

Front 23

LDL decrease relationship to statin dosing?

Back 23

largest decrease seen at starting dose;
each doubling of dose only produces 5-7% further reduction in LDL

Front 24

most efficacious drugs for lowering LDL?

Back 24

statins
(followed by sequestrants and cholesterol absorption blockers)

Front 25

additional benefits of statins?

Back 25

decrease CRP which is associated with increased risk of ischemic hear and cerebrovascular disease and increased plaque stability

Front 26

outcomes data for statins?

Back 26

primary and secondary CHD risk reduction;
slowing of progression and even regression of coronary atherosclerosis

Front 27

adverse reactions with statins?

Back 27

dose-related increase in myopathy
elevation of liver enzymes

Front 28

contraindications for statins?

Back 28

active or chronic liver disease
pregnancy
breast feeding

Front 29

lovastatin and simvastatin metabolized by and consequences?

Back 29

CYP3A4
subject to interactions with inhibitors or inducers

Front 30

fluvastatin metabolized by and consequence?

Back 30

CYP2C9
few interactions reported

Front 31

pravastatin and rosuvastatin metabolism and consequence?

Back 31

not significantly metabolized by CYP system;
least affected by other drugs

Front 32

may increase risk of myopathy seen with statins?

Back 32

concomitant use with fibrates and possible nicotinic acid

Front 33

ezetimibe?

Back 33

cholesterol absorption blocker

Front 34

ezetimibe mechanism of action?

Back 34

inhibits activity of NPC1L1 to reduce cholesterol absorption --> decreased dietary cholesterol to liver --> reduction in hepatic stores --> upregulation of LDL receptor --> increased cholesterol clearance from the blood

Front 35

NPC1L1 (niemann-pick C1-like protein)?

Back 35

sterol influx transporter located at apical membrane of enterocyte to actively facilitate the uptake of cholesterol by promoting passage of sterols across the brush border membrane of the enterocyte

Front 36

vytorin?

Back 36

fixed dose-dose combination of ezetimibe (10mg) and simvastatin (10,20,40,80mg)

Front 37

major uses of ezetimibe?

Back 37

primary hypercholesterolemia
homozygous familial hypercholesterolemia
homozygous sitosterolemia

Front 38

only medication approved for homozygous sitosterolemia?

Back 38

ezetimibe

Front 39

adverse effects of ezetimibe?

Back 39

troublesome diarrhea
depression

Front 40

precautions with ezetimibe?

Back 40

myalgia-rhabdomyolysis
liver enzymees
geriatrics
pregnancy and nursing mothers

Front 41

ezetimibe considerations in geriatric population?

Back 41

higher blood levels compared to younger so need lower dosing

Front 42

ezetimibe drug interactions?

Back 42

fibrates increase bioavailability and AUC
cholestyramine decrease absorption

Front 43

contraindications for ezetimibe?

Back 43

patients with moderate or severe liver disease or unexplained persistent elevations in serum transaminases

Front 44

nicotinic acid mechanism of action?

Back 44

binds GPR109A receptor to inhibit adenylyl cyclase --> inhibition of lipolysis --> decreased FFA levels --> substrate shortage for hepatic TAG synthesis --> less VLDL synthesized --> less LDL

Front 45

biological effects of nictonic acid?

Back 45

physiological
pharmacological

Front 46

physiological vs pharmacological effects of nicotinic acid?

Back 46

physiological: dose >15-20 mg/day in diet, nicotinamide is equivalent as a vitamin;
pharmacological: dose = 500-2000 mg/day, nicotinamide does not have same effects

Front 47

lipoprotein effects of nicotinic acid?

Back 47

decreased LDL
increased HDL
decreased TG
decreased LP(a)

Front 48

most efficacious agent for raising HDL?

Back 48

nicotinic acid

Front 49

major use of nicotinic acid?

Back 49

broad spectrum agent, can be used to decreased LDL, TG as well as increase HDL in variety of lipoprotein abnormalities

Front 50

outcomes data for nicotinic acid?

Back 50

secondary MI prevention and reduction of mortality

Front 51

adverse reactions with nicotinic acid?

Back 51

flushing
increase insulin resistance
induce hyperuricemia
headache
heartburn
indigestion
nausea
diarrhea
stomach pain

Front 52

niacin flushing onset and duration?

Back 52

within 20 min to 1 hr lasting 30-90 minutes;
associated with intense erythema, tingling, itching, and elevation of skin temp

Front 53

flushing mechanism?

Back 53

smae nicotinic acid receptor found in adipose tissue is found on Langerhans cells in the skin --> stimulation results in formation of prostaglandins

Front 54

minimize flushing?

Back 54

start low and gradually increase
attenuated by inhibition of COX with aspirin taken 30 min before

Front 55

tolerance to flushing?

Back 55

markedly decreases after several weeks of continuous use

Front 56

drug interaction of nicotinic acid?

Back 56

possible increase in myopathy when combined with a statin

Front 57

contraindications for nicotinic acid?

Back 57

active liver disease
acitve peptic ulcer
gouty arthritis
make diabetes control difficult (relative)

Front 58

fibric acid derivatives?

Back 58

fenofibrate
gemfibrozil
clofibrate
fenofibric acid

Front 59

fibrates mechanism of action?

Back 59

activation of PPARa

Front 60

fibrates effects?

Back 60

increase LDL clearance
reduces small dense LDL

Front 61

why is reduction of small dense LDL a good thing?

Back 61

larger, less dense LDL have high binding affinity for cellular LDL receptors and are less susceptible to oxidation

Front 62

which lipoproteins are fibrates alone more efficacious for improving than statins?

Back 62

lowering TG
raising HDL

Front 63

addition of statin to fibrate has what effect on TG levels?

Back 63

additional lowering

Front 64

addition of statin to fibrate has what effect on HDL?

Back 64

no additional raising

Front 65

major uses of fibrates?

Back 65

decrease TG
increase HDL
treatment of atherogenic dyslipidemia

Front 66

outcomes data for fibrates?

Back 66

primary prevention of CHD
prevention of CHD in type 2 DM
secondary prevention of cardiac events in men with low HDL

Front 67

fibrates adverse reactions?

Back 67

myalgia (gemfibrozil > fenofibrate)
elevated liver enzymes
possible gallstones (clofibrate)

Front 68

gemfibrozil drug interactions?

Back 68

inhibit CYP2C8 and glucuronidation of statins and increased their AUC

Front 69

fenofibrate drug interaction?

Back 69

prolong warfarin INR

Front 70

fibrates drug interactions?

Back 70

increase AUC of statins (gemfibrozil)
increase AUC of antidiabetics
prolong warfarin INR (fenofibrate)

Front 71

contraindications for fibrates?

Back 71

severe renal or hepatic dysfunction
preexisting gall bladder disease
nursing mothers

Front 72

lovaza?

Back 72

omega-3 polyunsaturated fatty acids: ethyl esters of EPA (eicosapentaenoic acid) and DHA (docosahexaenoic acid)

Front 73

potential PUFA mechanism?

Back 73

inhibition of acyl CoA:1,2-diacylglycerol acyltransferase;
increased mitochondrial and peroxisomal beta-oxidation in liver;
decreased lipogenesis in liver and increased plasma lipoprotein lipase activity;
reduce synthesis of TG in liver

Front 74

lipoprotein effects of PUFAs?

Back 74

increase LDL (but less atherogenic)
increase HDL
decrease TG

Front 75

major use of PUFAs?

Back 75

adjunct to diet for very high TG (4g/day);
reduce incidence of coronary heart disease and mortality (1g/day due to inhibiting platelet aggregation)

Front 76

outcomes data for PUFAs?

Back 76

secondary prevention: reduce cardiovascular death; sudden death; and combined endpoint of death, nonfatal MI and stroke

Front 77

PUFAs adverse effects?

Back 77

eructation
dyspepsia
taste perversion
worsening of glycemic control in diabetics
impaired homeostasis

Front 78

PUFA drug interactions?

Back 78

no significant
NO increased risk of myopathy with statins

Front 79

PUFA contraindications?

Back 79

hypersensitivity to any component of the medication

Front 80

orlistat?

Back 80

inhibitor of gastric and pancreatic lipase

Front 81

alli?

Back 81

1/2 dose orlistat available OTC

Front 82

orlistat mechanism?

Back 82

acts within lumen to inhibit gastric and pancreatic lipases --> lipases cannot hydrolyze dietary TG into FFA and monoglycerides to be absorbed --> undigested TG not absorbed

Front 83

orlistat indications?

Back 83

obesity management including weight loss and weight management when used in conjunction with a nutritionally balanced but reduce-calorie diet

Front 84

orlistat adverse effects?

Back 84

oily spotting
flatus with discharge
fecal urgency
fatty/oily stool
oily evacuation
increased defecation
fecal incontinence
(incidence increases with diet fat content)

Front 85

orlistat contraindications?

Back 85

chronic malabsorption syndrome
cholestasis
hypersensitvity
pregnancy
nursing women

Front 86

orlistat drug interactions?

Back 86

decreased plasma cyclosporine
fat soluble vitamins
warfarin (poor vit K absorption)
reduction in oral hypoglycemics or insulin (improved metabolic control in diabetics)