Anti-Hyperlipidemia Drugs

Question 1

Statins- available drugs

Answer 1

Lovastatin
Simavastatin
Atorvastatin
Fluvastatin
Rosuvastatin
Pravastatin

Question 2

Statins- Mech of action

Answer 2

• inhibits HMG-CoA reductase & triggers SREBP transcription factor
• leads to:

INCREASED LDL CLEARANCE
increased LDL-R expression

Question 3

Statins- Effect on Serum Lipids

Answer 3

decreased LDL (20-60%)
decreased TG (10-20%)
increased HDL (5-10%)

Question 4

Statins- Adverse Effects/Contraindications

Answer 4

RHABDOMYOLYSIS
muscle myalgia/myopathy
hepatitis

CONTRAINDICATED IN SEVERE LIVER DISEASE

Question 5

Statins- Drug Interactions- CYP34A inhibitors

Answer 5

increase [ ]s of L, S, and A

INCREASED RISK OF ADVERSE EFFECTS
ex: 
erythromycin
cyclosporin
ketaconazole
HIV protein inhibitors
grapefruit juice

Question 6

Statins- Drug interactions- CYP3A4 inducers

Answer 6

lower [ ]s of L, S, and A

DECREASED CLINICAL EFFICACY
ex:
phenytoin
phenobarbital 
rifampin

Question 7

Statins- Drug interactions- CYP2C9 inhibitors

Answer 7

increase [ ]s of F and R

ex.
ketoconazole
metronidazole

Question 8

Statins- Drug interactions- other

Answer 8

Gemfibrozil

• decreases OATP2, decreases glucoronidation= INCREASES [ALL STATINS]

Question 9

Bile Acid Binding Resins- available drugs

Answer 9

Cholestryramine
Colestipol
Colesevelam

Question 10

Bile Acid Binding Resins- Indications

Answer 10

high LDL

Question 11

Statins- Indications

Answer 11

high LDL

Question 12

Bile Acid Binding Resins- Mech of Action

Answer 12

binds bile acids and prevents reabsorption

= increased chol 7alpha-hydroxylase–> decreased cholesterol–> increased LDLR–> INCREASED LDL CLEARANCE

Question 13

Bile Acid Binding Resins- Effect on serum lipids

Answer 13

decreased LDL (10-25%)

Question 14

Bile Acid Binding Resins- Adverse Effects/Contraindications

Answer 14

CAN INCREASE TG LEVELS IN HYPERTRIGLYCERIDEMIA

CONTRAINDICATED WHEN TG > 400MG/DL

Question 15

Bile Acid Binding Resins- Drug interactions

Answer 15

cholestyramine/colestipol interfere w/ absorption of a number of drugs

ex. 
warfarin
phenobarbital
digoxin
tetracycline

Question 16

Ezetimibe- Indications

Answer 16

high LDL

Question 17

Ezetimibe- Mech of Action

Answer 17

inhibits intestinal absorption of cholesterol (via NPCL1)

= DECREASED HEPATIC CHOLESTEROL–> increased LDL-R expression–> INCREASED LDL CLEARANCE

Question 18

Ezetimibe- Effect on serum lipids

Answer 18

decreased LDL (about 18%)

Question 19

Ezetimibe- Adverse Effects/Contraindications

Answer 19

• generally well tolerated
• flatulence and diarrhea most common
• myalgia and rhabdomyolysis can occur, but is very rare
• low incidence of impaired liver function (reversible)

Question 20

Ezetimibe- Drug interactions

Answer 20

bile acid resins interfere w/ Ezetimibe absorption

Question 21

Niacin- Indications

Answer 21

high VLDL
high LDL
low HDL

Question 22

Niacin- Mech of Action

Answer 22

1. acts via GPCR GPR109A to decrease lipolysis in adiposites
   = DECREASED [FFA]–> DECREASED VLDL
2. increased apoAI expression
   = INCREASED HDL PRODUCTION
3. DECREASED LP-A–> DECREASED THROMBOSIS

Question 23

Niacin- Effect on serum lipids

Answer 23

decreased TG (30-80%)
decreased LDL (10-20%)
increased HDL (10-30%)

Question 24

Niacin- Adverse Effects/Contraindications

Answer 24

• SKIN FLUSHING (TX-NSAID)
• RISK OF GOUT
• EXACERBATES PEPTIC ULCERS
• risk of hyperglycemia
• hepatitis

Question 25

Niacin- Drug interactions

Answer 25

none given

Question 26

Fibrates- available drugs

Answer 26

gemfibrozil | fenofibrate

Question 27

Fibrates- Indications

Answer 27

high VLDL | low HDL

Question 28

Fibrates- Mech of Action

Answer 28

LIGANDS FOR PPAR-ALPHA TRANSCRIPTION FACTOR 1. decreased Apo C3, increased LPL expression, increased fatty acid oxidation = DECREASED VLDL SYNTHESIS, INCREASED VLDL CLEARANCE 2. increased ApoAI expression = INCREASED HDL PRODUCTION

Question 29

Fibrates- Effect on serum lipids

Answer 29

``` decreased TG (40-60%) decreased LDL (10-20%) increased HDL (10-20%) ```

Question 30

Fibrates- Adverse Effects/Contraindications

Answer 30

INCREASED GALLSTONES RHABDOMYOLYSIS (more common with gemfibrozil) hepatitis myopathy CONTRAINDICATED IN SEVERE RENAL/HEPATIC DISEASE

Question 31

Fibrates- Drug interactions

Answer 31

Strong protein binders: - increased warfarin--> increased risk of bleeding - increased sulfonylureas--> increased hypoglycemia STATIN interaction: - inhibit OATP2/glucoronidation - increased [statins]--> increased rhabdomyolysis, esp. gemfibrozil