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Advanced Pharm > Lipid Lowering drugs > Flashcards

Lipid Lowering drugs Flashcards

1
Q

What is the normal physiologic role of lipoproteins?

A
  • triglycerides are an essential energy source
  • cholesterol is necessary to produce:
    • cell membranes
    • bile acids
    • steroid hormones
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2
Q

What are lipoproteins?

A
  • a carrier required to transport lipids to and from cells in the periphery
  • produced via an exogenous pathway
    • dietary fat
    • cholesterol
    • fat soluble vitamins
  • Or produced endogenously
    • synthesized in liver
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3
Q

Order the density of lipoproteins from lowest to highest

A
  • chylomicrons
  • very low density lipoproteins
  • intermediate density lipoproteins
  • low density lipoproteins
    • bad b/c they carry cholesterol out to periphery
  • high density lipoproteins
    • good b/c they carry cholesterol back to liver
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4
Q

Why is hyperlipidemia a problem?

A
  • High cholesterol is associated with increased CAD
  • High triglycerides are associated with pancreatitis
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5
Q

How is atherosclerosis formed?

A
  • When there is excess LDL, the LDL molecules will deposit into the tunica intima
    • the LDL is then oxidized, which attracts macrophages
  • The macrophages will take up the LDLs and will become foam cells
    • foam cells promote migration of smooth muscle cells from the tunica media to the tunica intima and smooth muscle cell proliferation
  • Smooth cell proliferation causes increased formation of collagen, which causes hardening
  • during this process, foam cells will die, releasing lipid content and driving the growth of the plaque
  • the plaque can rupture, leading to thrombosis
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6
Q

What is primary hyperlipidemia?

A
  • genetic heterozygous condition resulting in elevated total cholesterol level or triglyceride level
  • often called Familial hypercholetolemia or familial hypertriglyceridemia
  • total cholesterol usually >200, triglycerides often >500
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7
Q

What is secondary hyperlipidemia?

A
  • Usually associated with another disease
    • DM
    • hypothyroidism
    • obstructive liver disease
    • chronic renal failure
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8
Q

What drugs can increase LDL and decrease HDL?

A
  • progestins
  • corticosteroids
  • anabolic steroids
  • protease inhibitors
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9
Q

What are desireable levels for

total cholesterol?

HDL?

LDL?

A
  • Total cholesterol:
    • desireable: <200
    • high: >240
  • HDL:
    • low <40
    • high >60
  • LDL
    • optimal <100
    • high 160-189
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10
Q

What are the newest ACC/AHA guidelines?

What were the previous guidelines?

A
  • the newest guidelines focus on the relative reduction of ASCVD (atherosclerotic cardiovascular disease) using statins
  • Previous guidelines focused on screening pts for hyperlipidemia and treating it to try to bring it down to a goal LDL level
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11
Q

How is ASCVD assessed?

A
  • History of choronary heart disease
    • angina
    • MI (anybody who has had an MI should go on statins)
    • coronary interventions (PTCA, stents, CABG)
  • Peripheral arterial disease
    • peripheral areterial disease
    • symptomatic carotid artery disease
    • abdominal aortic aneurysm
  • Risk factors (separate card)
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12
Q

What are the risk factors for ASCVD?

A
  • Gender
  • age- older
  • race
  • total cholesterol
  • HDL cholesterol- less concern if HDL is robust
  • BP- CV risk doubles with every 20 pt increase in BP
  • treatment for high blood pressure
  • DM
  • smoking
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13
Q

What are the four groups that warrant statin therapy?

A
  • Clinical ASCVD
  • LDL > 189
  • Ppl 40-75 with D< and LDL 70-189 without ASCVD
  • ppl 40-75 with DM and LDL 70-189 and a 10 year ASCVD risk of 7.5% or higher
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14
Q

What is the intensity of statin therapy based on?

A
  • Presence of clinical ASCVD
  • risk of developing ASCVD
  • presence of DM with/without hyperlipidemia
  • presence of isolated hyperlipidemia (genetic)
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15
Q

How much does High intensity statin therapy lower LDL?

moderate insensity?

low intensity?

(chart)

A
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16
Q

In what situations would the addition of a non-statin be considered?

A
  • High risk patients who have a less than anticipated response to statins
  • patients that are unable to tolerate the recommended intensity of a statin or are completely intolerant
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17
Q

What are secondary treatment goals?

A
  • Treat elevated triglycerides
    • if triglycerides are > 200 and LDL goal has been achieved, add additional treatment for TGs
  • Treat low HDLs (<40)
    • If HDLs are <40 and LDL and TG goals have been achieved, add another treatment for HDLs
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18
Q

What are statins?

How do they work?

effects?

A
  • HMG-COA reductase inhibitors
    • inhibit the enzyme that catalyzes the rate-limiting step in the formation of cholesterol by the liver
    • specifically inhibits the conversion of HMG-COA to mevalonate
  • Effect is to:
    • decrease cholesterol synthesis in liver
    • enhance LDL receptor expression which increases LDL uptake in liver
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19
Q

How much do statins decrease LDLs?

TGs?

increase HDLs?

A
  • decrease LDLs 20-60%
  • decrease TGs 10-20%
  • increase HDLs about 10%
20
Q

What are the statin agents?

A
  • Lovastatin (Mevacor)
  • Simvistatin (zocor)
  • Atorvastaton
  • Rosuvastatin (Crestor)
  • Pravastatin (Pravachol)
  • Fluvastatin (Lescol)
21
Q

What are some other beneficial effects of statins besides normalization of lipids?

A
  • promote plaque stability
    • decreases M&M when administered perioperatively to a high risk patient
  • Antioxidant, anti-inflammatory, vasodilatory
  • Reduction in CV events even in pts with normal LDL levels
    • also helpful in diabetics
  • increased bone formation
22
Q

What are the pharmacokinetics of statins?

A
  • Lovastatin and simvastatin are prodrugs
  • Highly PB (except pravastatin)
  • extensive CYP450 metabolisme (except pravastatin)
  • E1/2t: 1-4 hours (clinical effects last for 24 hours)
    • atorvastatin 14 hours
23
Q

What is the incidence of side effects of statins?

What are the common side effects of statins?

The rare ones?

A
  • 5%- similar to placebo
  • common
    • HA
    • rash
    • GI disturbances
    • myalgias
  • Rare
    • hepatotoxicity
    • peripheral neuropathy
    • myopathy/rhabdomyalysis- can be fatal
24
Q

Who is at higher risk of myopathies with statins?

A
  • pts with pre-existing muscle disease
  • >80 yrs
  • female
  • asians
  • small body frame and frailty
  • impaired renal or hepatic system
  • alcohol abuse
  • hypothyroid
  • high statin levels
25
Q

What pregnancy category are statins?

A

Category X- the fetus NEEDS cholesterol/triglycerides to grow

26
Q

What are the drugs we care about regarding statin interactions?

A
  • Ketoconazole
  • erythromycin
  • clarithromycin
  • amiodarone
  • protease inhibitors
27
Q

How do bile acid sequestrants/resins work?

What is the effect?

A
  • It is a non-absorbable resin that binds bile acids and other substances in the GI tract, preventing absorption and promoting GI excretion
  • results in the liver using hepatic cholesterol to produce more bile acids and increased LDL receptor expression on hepatocytes
  • effect is to decrease LDLs, increase HDLs, no change to TGs
28
Q

What are some of the bile acid sequestrant drugs?

A

cholestyramine (Questran)

Colestipol

colesevelam

29
Q

How are bile sequestrants dosed?

A
  • It is a powder that gets mixed with liquid
  • take 30 min. before, during, or after a meal
  • increase dose gradually
30
Q

What are some bile acid sequestrant drug interactions?

A
  • Can interfere with absorption and/or form complexes with many PO meds
    • synthroid
    • oral contraception
    • sulfonylurea antibiotics
    • phenytoin
    • thiazide diuretics
    • fat soluble vitamins
31
Q

What are some advers effects of bile acid sequestrants?

A
  • GI- severe constipation, flatulence, N/V
    • high fiber diet
    • stool softener
  • reduced folate levels with long term use
  • cholestyramine (chloride) hyperchoremic acidosis
    • seen in young or small pts
32
Q

How does Nicotinic acid (Niacin) work to improve cholesterol?

What is the effect?

A
  • MOA unclear: reduces the production of VLDLs
    • works on liver and adipose tissue to inhibit TG production
    • increases HDLs more effectively than any other drug, how it does this is unknown
  • Effect:
    • reduces LDLs and TGs
    • increases HDLs
33
Q

What are some nicotinic acid agents?

A
  • Nicotinic acid in immediate release, extended release, sustained release
  • Niaspan
34
Q

How much does niacin improve long term outcomes?

A

It does little to improve long term outcomes. “Reduction in risk factors does not translate to reduction in actual risk”

35
Q

What are the adverse effects of Niacin?

A
  • skin flushing and itching
    • can pretreat with aspirin 30 min before dose
  • GI discomfort
  • hepatotoxicity- assess liver function regularly
  • hyperglycemia
  • gouty arthritis
  • can raise blood levels of uric acid
    • check kidney function, encourage 2-3 L/day water intake
36
Q

How is Niacin dosed?

A
  • gradually increase dose
  • titrate: 1.5-2 g/day
  • divided doses with meals
  • ASA prior to dosing
  • avoid hot fluids prior to use
  • contains yellow dye #5
37
Q

How do Fibric acid derivatives work?

How do they affect the levels of TGs, HDLs, and LDLs?

A
  • MOA: Interacts with a receptor (PPAR alpha) that increases synthesis of lipoprotein lipase (LPL)
    • and decreases an apolipoprotein that inhibits LPL
  • Increases lopolysis of triglycerides
  • **most effective drugs available to decrease TGs (40-50%)
  • Can increase HDLs 15-25%
  • Very little decrease in LDLs
38
Q

What are the three Fibric acid derivative drugs?

A
  • Gemfibrozil (Lipod)
  • Fenofibrate (Tricor)
  • Fenofibric acid (TriLipix)
39
Q

What are the adverse drug reactions with Fibric acid derivatives?

A
  • displaces warfarin from albumin- can increase risk of bleeding
    • measure INR
  • rashes
  • GI disturbances
  • HA
  • rhabdo & myopathy- do not give with statins
  • Gallstones
  • hepatotoxic- check LFTs
40
Q

How does Exetimibe (Zetia) work?

A
  • By inhibiting cholesterol and phytosterol absorption from the brush border of the intestines
    • disrupts complex btw annexin-2 and cavolin-1 proteins
    • increases the expression of LDL receptors
  • No affect on absorption of fat soluble vitamins (A,D,E,K)
  • No affect on CYP450 enzymes
  • intended for use in conjunction with a statin
41
Q

What did the IMPROVE-IT trial find?

A
  • IMPROVE-IT added Exetimibe to simvistatin and reduced LDL by 24%
  • also demonstrated a 2% reduction in the primary composite end point of CV death, major coronary events, or nonfatal CVA
  • *unclear if this is b/c of overall lowering of LDL or the addition of exetimbe but it diminishes the idea that only statins provide a mortality benefit
  • **Other studies have not shown a mortality benefit
42
Q

What is the LDL deduction of a statin combined with Exetimibe?

A statin with a bile acid sequestant?

A statin with a fibric acid derivative?

A statin and Niacin?

A
    • Extimibe = 25% reduction in LDL
    • bile acid sequestant = 8-16% reduction in LDL
    • Fibric acid derivative = decreases triglycerides
      • increased risk of myopathies
      • contraindicated with hepatic disease
    • Niacin = increased risk of hepatic dysfunction
43
Q

What is the only lipid lowering medication class that is safe during pregnancy?

A

Bile acid-binding resins

44
Q

Apply all your knowledge to describe what is happening in this picture.

A

If you dont know this from the other 40 cards you just learned, start over.

45
Q

What are apolipoproteins and how might useful?

A
  • Apolipoproteins are embedded in the outer layer of the phospholipid bilayer that surrounds the cholesterol (all types)
    • they are necessary for assembly, provide sturcture, activate enzymes, and act as receptor ligands for cellular uptake
    • They are also the culprit that binds to the arterial wall, beginning the oxidative and inflammatory process that really gets the atherogenesis going
  • Apolipopotein B seems to be linked with cardiovascular disease
    • monitoring apolipoprotein B may be useful as an additional means of monitoring the efficacy of a given treatment
46
Q

What is Mipomerson?

A
  • An antisense oligonucleotide targeted to human mRNA for apolipoprotein B-100
  • if mipomerson combines to apoB mRNA, will result in degredation and loss of translation of the apoB protein
  • FDA approved for familial hyperlipidemia
  • Adverse affects: hepatic dysfunction, steatosis, flu-like symptoms, Nausea, HA
    • hepatotoxicity = black box warning
47
Q

What is lopitamide?

A
  • A Microsomal triglyceride transfer protein inhibitor
  • presents assembly of apoB-containing lipoproteins in enterocytes and hepatocytes
    • inhibits the synthesis of chylomicrons and VLDL in liver
    • up to 50% decrease in plasma LDL levels
  • Adverse affect: hepatic steatosis

Advanced Pharm (27 decks)

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