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Pharmacology > Hyperlipidemia > Flashcards

Hyperlipidemia Flashcards

1
Q

What is the major carrier of cholesterol in circulation?

A

LDL-C, contains 75% of total cholesterol, most atherogenic

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2
Q

_____ protects against development of atherosclerosis & removes free cholesterol from periphery & transports it back to liver for removal.

A

HDL-C

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3
Q

What carries cholesterol & triglycerides made in liver to sites of utilization?

A

VLDL-C

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4
Q

_____ are synthesized in intestines from dietary fat, are comprised of mostly triglycerides & transport dietary cholesterol & triglycerides?

A

Chilomicrons

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5
Q

Steps of pt evaluation for cholesterol screening (5)

A
  1. Determine lipoprotein level
  2. Determine presence of ASCVD (Atherosclerotic Caridovascular Disease)
  3. If no ASCVD, identify presence of ASCVD risk equivalents
  4. If no ASCVD or ASCVD risks, calculate 10 yr ASCVD risk factors
  5. If no ASCVD, ASCVD risks & 10 yr risk is >7.5, determine major ASCVD risk factors
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6
Q

Non-fasting lipoprotein panel should only evaluate the _____ and _____.

A

Total cholesterol & HDL-C

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7
Q

A fasting cholesterol evaluation is recommended if total cholesterol is _____ or _____

A

> 200mg/dL or HDL-C <40mg/dL

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8
Q

What is fasting defined as?

A

No oral intake for 8 hrs

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9
Q

In pts w/ ACS a lipoprotein sample should be obtained w/i _____ hrs.

A

24 hrs

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10
Q

LDL-C will be falsely _____ after 24 hrs for up to 4-6 weeks in pts w/ ACS

A

Low

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11
Q

How often, in all pts, should a fasting lipoprotein panel be checked?

A

Once every 5 years

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12
Q

What diseases indicate presence of ASCVD?

A

Coronary heart dz (ACS, hx of MI/UA/SA/PCI/CABG)

Cerebrovascular dz (stroke/TIA/>50% carotid occlusion)
PAD
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13
Q

What are the ASCVD risk equivalents?

A

DM 1 or 2

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14
Q

What are the components of ASCVD risk calculation?

A
  • Gender
  • Age
  • Race
  • Total cholesterol
  • HDL-C
  • Systolic BP +/- treatment
  • DM
  • Smoking status
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15
Q

What are the ASCVD risk factors?

A
  • 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
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16
Q

nicotinic acid (Niacin) MOA

A

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.

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17
Q

Lipid effects of Niacin

A

LDL decreased by 5-25%
HDL decreased by 15-35%
TG decreased by 20-50%

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18
Q

nicotinic acid (Niacin) dosing/admin

A

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

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19
Q

nicotinic acid contraindications

A
  • Liver dz
  • Elevated LFTs
  • GB dz
  • Hypotension
  • DM (uncontrolled)
  • Active PUD
  • Hyperuricemia
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20
Q

nicotinic acid adverse effects

A
  • 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
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21
Q

nicotinic acid monitoring

A

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

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22
Q

Bile acid sequestrant MOA

A

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

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23
Q

Bile acid sequestrant lipoprotein effects

A

LDL decrease by 15-30%
HDL decrese by 3-5%
TG no change or increased

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24
Q

colestipol (Colestid) dosing/admin

A

Bile acid sequestrant
1g tablet/suspension/5g packet/scoop
2-16g/day QD/BID
Titrate @ 1-2 mo interval

25
Q

cholestyramine (Questran)

A

4g cholestyramine/9g resin

4-24g/day (1-6 packets/scoops)

26
Q

colesevelam (WelChol)

A

625mg PO tab
1.875g (3 tabs) BID or 3.75mg (6 tabs) QD
Max effect in 2 wks

27
Q

Bile acid sequestrant contraindications

A
  • familial dysbetalipoprotemia
  • TG >400mg/dL absolute; >200mg/dL relative
  • biliary obstruction
  • hypersensitivity to bile acid sequestrants
28
Q

Bile acid sequestrant adverse effects

A

GI: constipation, abd discomfort, epigast fullness, belching, flatulence - tx w/ incr fluid, fiber, stool softeners

Endocrine: incr TG

Heme: bleeding - tx w/ vitamin K

29
Q

Bile acid sequestrant monitoring

A

LFT anually

30
Q

Fibric acid derivatives MOA

A

Stimulate lipoprotein lipase activity thus hydrolyzing TG in chylomicrons & VLDL and hastening their removal from plasma

31
Q

Fibric acid derivative lipoprotein effects

A

LDL decreased by 5-20%
HDL decreased by 10-20%
TG decreased by 20-50%

32
Q

gemfibrozil (Lopid) dosing/admin

A

Fibric acid derivative

600mg PO BID 30 mins before meals

33
Q

fenofibrate (Tricor)

A

67-200mg PO QD

34
Q

clofibrate (Atromid-S)

A

2000mg/day in 2-4 divide doses

35
Q

Fibric acid derivative contraindications

A
  • Hepatic dysfunction
  • Elevated LFTs
  • Primary biliary cirrhosis or preexisting cholelithiasis
  • Renal dysfunction (SCr>2.0mg/dL)
36
Q

Fibric acid derivative adverse effects

A

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)

37
Q

Fibric acid derivative drug interactions - anticoagulants

A

Monitor and adjust anticoagulant dose. Gemfibrozil may enhance pharmacologic effect

38
Q

Fibric acid derivative drug interactions - HMG-CoA reductase inhibitors

A

Increased risk of myopathy and rhabdo after 3 wks of lovastatin & gemfibrozil (decrease the max dose of statins used)

39
Q

Fibric acid derivative monitoring

A

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

40
Q

HMG co-reductase inhibitor MOA

A

Inhibits enzyme HMG co-reductase (rate limiting step in cholesterol synthesis). Decreases intracellular cholesterol & causes the cell to increase # of LDL receptors.

41
Q

HMG-CoA reudctase inhib lipoprotein effects

A

LDL decrease by 18-55%
HDL decrease by 5-15%
TG decrease by 7-30%

42
Q

lovastatin (Mevacor) dosing/admin

A

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)

43
Q

pravastatin (Pravachol)

A

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

44
Q

simvastatin (Zocor)

A

HMG-CoA reductase inhib

24-40% lipid reduction

5-20mg/d, max 80mg/d; @ bedtime (qHS)

45
Q

atrovastatin (Lipitor)

A

10-80mg QD

41-61% lipid reduction

46
Q

rosuvastatin (Crestor)

A

5-10mg QD

45-63% lipid reduction

47
Q

HMG-CoA reductase inhib contraindications

A
  • Hypersensitivity
  • Liver dz
  • Elevated LFTs
48
Q

HMG-CoA reductase monitoring

A

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

49
Q

HMG-CoA adverse effects

A

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

50
Q

Atorvastatin, Lovastatin, Simvastatin drug interactions

A 
3A4 Inhibitor:
Cyclosporin
Azole antifungals
Macrolide abx
Grapefruit juice
Cimetidine
Protease inhibitors
Amiodarone
Ca channel blockers
51
Q

Fluvastatin

Rosuvastatin drug interactions

A 
2C9 Inhibitor:
Cimetidine
Amiodarone
TMP/SMX
Omeprazole
Fluconazole
Fluvoxamine
Ritonavir
Zafirlukast
52
Q

ezetimibe (Zetia) MOA

A

Decreased absorption of cholesterol from intestines by blocking the protein transport system that brings cholesterol into the intestinal cells.

53
Q

What is different about the duration of action of ezetimibe (Zetia)?

A

Enterohepatic recycling of drug prolongs duration of action. Effective t1/2 = 28-30h

54
Q

ezetimibe (Zetia) clinical efficacy

A

Flat dose response curve
10mg/day decreases LDL by 10% & increased HDL
Decreased triglycerides
Peak effect in 2 weeks

55
Q

What is the benefit of adding ezetimibe (Zetia) to a statin?

A

Lowering of LDL by additional 15-20%

56
Q

ezetimibe (Zetia) drug interactions

A

Fenofibrate, gemfibrozil increases ezetimibe levels by 50%

57
Q

ezetimibe (Zetia) adverse effects

A 
Chest pain
Arthralgia
Diarrhea
Dizziness
HA
*no hepatotoxicity or skeletal muscle dysfunction
58
Q

ezetimibe (Zetia) dosing admin

A

10mg BID w/ or w/o food

Pharmacology (10 decks)

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