Drug Therapy for Lipid Disorders

Question 1

Statin Action

Answer 1

Inhibit HMG CoA Reductase, rate-limiting enzyme in chol biosynth

Question 2

2 Other Things from HMG CoA Pathway

Answer 2

Prenylation of signalling peptides like ras and raf
Ubiquinone synth (CoQ-10, etc)

Question 3

Effect of LDL-Reducing Drugs on Liver

Answer 3

Increase LDL R density, so increase clearance

Question 4

CYP450 3A4 (& 2 statins that follow its metabolism)

Answer 4

Involved in many drug clearance and inhibited by a lot of drugs too. Atorvastatin and simvastatin

Question 5

Statin w/out Renal Clearance

Answer 5

Atorvastatin

Question 6

Longest halflife Statin

Answer 6

Pravastatin

Question 7

2 Statins w/ Greatest Degree of LDL Lowering

Answer 7

Atorvastatin and rosuvastatin

Question 8

LDL Lowering Dosing

Answer 8

First use dose to get to 30% reduction, then 6% increase for each doubling

Question 9

3 Pleiotropic Effects of Statins

Answer 9

Increased NO/endothelial function
Acute anti-inflammatory, maybe most important. Reduced CRP
Maybe antiox, prevent LDL peroxidation

Question 10

3 Adverse Effects of Statins (& major point)

Answer 10

Liver Enzyme Elevations
Myopathy
Mildly increased diabetes occurrence
Effects are rare and mild

Question 11

2 Medicines that Interfere w/ Statin Catabolism

Answer 11

Cyclosporin

Gemfibrozil

Question 12

Bile Acid Sequestrant Mech

Answer 12

Inhibits bile return to liver, so liver is forced to use up more chol to synth BAs

Question 13

Colesevelam (Welchol)

Answer 13

Dissolvable BAS

Question 14

New Discovered Effect of BAS

Answer 14

Antihyperglycemic action

Question 15

Importance of BAS Effects

Answer 15

Lower LDL and have been shown to have reduced CHD mortality - so without pleiotropic effects of statins, gives credence to hypothesis that lower LDL leads to lower CHD

Question 16

Plant Sterols and Sterol Esters (Stanols)

Answer 16

Reduce cholesterol absorption by interfering w/ micelle formation. Not great

Question 17

Ezetimibe (Zetia) (2)

Answer 17

Specifically inhibits cholesterol absorption channel NPC1L1 and reduces LDL. Well tolerated so usually 1st addition to statin

Question 18

Fibric Acid Derivates (what they’re for, how they work, and 2 of them)

Answer 18

Hypertriglyceridemia treatment mainly by increasing lipoprotein lipase (so it won’t work in LPL deficient individuals).
Gemfibrozil and fenofibrate

Question 19

Fenofibrate vs. Gemfibrozil (2)

Answer 19

Fenofibrate over gemfibrozil w/ statin bc less effect on statin clearance
But Gemfibrozil has been better shown to reduce coronary events

Question 20

Omega 3 FAs (O3FA)

Answer 20

Reduce TGs at very high doses

Question 21

Lovasa

Answer 21

Prescription O3FA

Question 22

Niacin (benefit and problem)

Answer 22

Raises HDL cholesterol, but has huge problem with flushing