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DT III Exam 1 > Drugs to lower Cholesterol and Triglycerides > Flashcards

Drugs to lower Cholesterol and Triglycerides Flashcards

1
Q

First line therapy to lower cholesterol and triglycerides

A

Diet therapy

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2
Q

Resin

A

Cholestyramine, Colesevelam, Colestipol

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3
Q

Cholestyramine

A

Resin

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4
Q

Cholesevelam

A

Resin

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5
Q

Colestipol

A

Resin

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6
Q

Resin: MoA

A

Increase fecal excretion of bile acids
Decrease negative feedback by 7 alpha hydroxylase
Increase conversion of hepatic cholesterol to bile acids
Increase # of hepatic LDL receptors (lower LDL-C)

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7
Q

Bile acid negative feedback

A

7 alpha hydroxylase

Resins remove negative feedback

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8
Q

Resins: contra

A

Statins

Resin can be used in pregnancy

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9
Q

Resin: ADR

A

GI issues (bloating, constipation, stomach pain)

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10
Q

Resin: metabolism

A

Must be staggered with other drugs, especially fat soluble vitamins (ADEK) and acidic anionic drugs
Not absorbed in GI tract or biotransformed by liver
{No alteration with P450 or binding displacement}

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11
Q

Statins (HMG CoA reductase inhibitors)

A

Atorvastatin, Simvastatin, Lovastatin, Rosuvastatin, Pravastatin, Fluvastatin, Pitavastatin

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12
Q

“-statin”

A

Statins

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13
Q

Statin: MoA

A

Reversible competitive inhibitors of cholesterol biosynthesis at liver
(HMG CoA >|| Mevalonate > Cholesterol}
Increase # of hepatic plasma LDL
Lower cholesterol levels

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14
Q

Statins that lower cholesterol and triglycerides

A

Atorvastin, Rosuvastin

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15
Q

Statin: ADR

A 
Elevate plasma ALT/AST
Increase CPK (creatine phosphokinase)
Myalgia {must withdraw if happens}
(Myalgia less with Fluva and Prava}
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16
Q

Statin: contra

A

Pregnancy
Nursing mother
Acute liver disease {ALT/ AST}

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17
Q

Statins: pediatric use

A

8 yo: Pravastatin

10 yo: Other statins

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18
Q

Statin: administration and bioavailability

A

Midnight-2AM (peak cholesterol synthesis)
Higher bioavailability with food: Fluva, Lova, Simva
Lower bioavailability with food: Prava, Pitava {Don’t eat Peas at dinner}

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19
Q

Atovastatin and Rosuvastatin: MoA

A

Longer half life
Higher increase in LDL receptor
Increase clearance of IDL (ApoE)

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20
Q

Statin: prodrug

A

Lovastatin, Simvastatin

{Converted by intestinal carboxyesterase and CYP3A4}

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21
Q

Statin: CYP3A4

A

Atorva, Lova, Simva

Avoid CYP3A4 inhibitors and Grapefruit juice

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22
Q

Statin: CYP2CP

A

Rosuva, Fluva

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23
Q

Statin: CYP2D6

A

Simvastatin

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24
Q

Statin: polymorphism

A

Simvastatin induced muscle pain
Higher with CYP2D6*4 allele (higher half life)
SCLO1B1 SNP lowers hepatic uptake higher plasma levels

25
Q

Ezetimibe: MoA

A

Inhibit cholesterol absorption at brush border of small intestine
Inhibit cholesterol absorption at enterocytes
Inhibit NPC1L1 transporter protein
Target dietary cholesterol
Lower LDL-C by 20%
Better with statin than statin*2

26
Q

Ezetimibe: ADR

A

Minimal GI side effects, diarrhea after fatty meal

27
Q

Ezetimibe: contra

A

Hepatic dysfunction (enterohepatic recirculation)
Resins
Stain increase transaminase levels

28
Q

PCSK9 inhibitors

A

Alirocumab, Evolocumab

Proprotein convertase subtilisin kexin 9 inhibitors

29
Q

Alirocumab

A

PCSK9 inhibitors

30
Q

Evolocumab

A

PCSK9 inhibitors

31
Q

PCSK9 inhibitors: MoA

A

More LDL receptor # than statin

Subcutaneous injection per 2-4wk

32
Q

PCSK9: ADR

A

Hypersensitivity

33
Q

Fibrates

A

Gemfibrozil, Clofibrate, Fenofibrate {-fib-}

34
Q

Gemfibrozil

A

Fibrate

35
Q

Clofibrate

A

Fibrate

36
Q

Fenofibrate

A

Fibrate

37
Q

Fibrates: MoA

A

Lower triglycerides
Increase HDL by increasing APO AI and AII
Binds to PPAR alpha & stimulates fatty acid oxidation)
PPAR alpha reduces apoCII expression
Result in increased lipoprotein lipase activity (decrease APO CIII)
PPAR decrease hepatic production of VLDL

38
Q

ApoCIII function

A

Inhibit lipoprotein lipase and VLDL ligand clearance

Reduced by Fibrates

39
Q

Fibrates: ADR

A

Gallstone risk (Clofibrate only)
Myopathy when combined with Statin
(worse with Gem and Clo) (least with Feno)
{Gembifrozil inhibit OATP2 (Atova, Prava, Rosuvastatins)}

40
Q

Fibrate: contra

A

Liver dysfunction
Renal disease
Preexisting gallbladder disease (Clofibrate)

41
Q

Nicotinic acid: MoA

A

Decrease production of hepatic VLDL
Inhibit lipolysis, decrease FFA delivery to liver
Inhibit hormone sensitive lipase in adipose tissue
Increase lipoprotein lipase activity (increase VLDL clearance)

42
Q

Nicotinic acid: use

A

Lower triglycerides and cholesterol (both)

43
Q

Nicotinic acid: ADR

A

Itching and Flushing (alleviated by Aspirin)
{inhibit prostaglandin synthesis causing flushing}
Elevate ALT/ AST (stop if x3 elevated)
Peptic ulcer
Hyperuricemia and glucose intolerance

44
Q

Nicotinic acid: cautions

A

Monitor Creatine kinase (CK) when combined with Statin
Can’t interchange dose between immediate/ extended release
Titration over 4wk

45
Q

Nicotinic acid: contra

A

Bleeding disorders (peptic ulcer with statin)
Active liver disease
Active peptic ulcer

46
Q

Familial hyperchylomicronemia

A

Type I
Elevated Chylomicrons and triglycerides
Defect in Lipoprotein lipase activity or in Apo C-II
Control with diet therapy, Fibrates (Gem), Nicotinic acid

47
Q

Familial hypercholesterolemia

A 
Type IIa
Elevated Cholesterol and LDL
Increased CVD risk
Decreased LDL clearance
Control with Statins, Ezetimibe, Resins
48
Q

Familial combined hyperlipoproteinemia

A

Type IIb
Elevated Triglycerides (VLDL) and Cholesterol (LDL)
Control with Statin (Atorva, Lova, Rosuva), Nicotinic acid

49
Q

Familial dysbetalipoproteinemia

A

Type III
Elavated Triglycerides, Cholesterol, IDL, Chylomicron remnants
Decreased VLDL catabolism= IDL accumulation
ApoE2
Increased VLDL production
Most sensitive to Fibrates

50
Q

Familial hypertriglyceridemia

A

Type IV
Elevated Triglycerides and VLDL
Associated with Hyperuricemia and Glucose intolerance
Control with Fibrates
Uric acid and blood glucose control worse with Nicotinic acid

51
Q

Secondary cause of cholesterol elevation

A

Biliary disease, Renal disease, Hypothyroidism, Diabetes mellitus

52
Q

Secondary cause of Triglycerides elevation

A

Alcoholism, Renal disease, Diabetes mellitus

53
Q

Elevation of lipids by Thiazide diuretics

A

Elevate Cholesterol and Triglycerides

54
Q

Elevation of lipids by non-specific beta blockers

A

Elevate triglycerides

Decrease HDL

55
Q

Lipids elevated by Oral contraceptive

A

Elevate Triglycerides

Estrogen/ Progesterone comb

56
Q

Drugs that lower cholesterol

A

Statin, Resins, Nicotinic acid

57
Q

For patients with diabetics taking oral hypoglycemic agents

A

Use Lovastatin

{Nicotinic acid makes diabetes worse}

58
Q

Avoided in first trimester of pregnancy

A

Statins (in all trimester)

DT III Exam 1 (5 decks)

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