04.07 - Lipids (Elam) Flashcards
Defect in Primary Chylomicronemia
Defective removal of CM (apoCII, LPL defect)
(according to elam) what drug to give if hyper-tg-emic
Statins
(According to firecracker) To decrease TG’s, use:
Fibrates (and Niacin)
2 Fibrates
Gemfibrozil, Fenofibrate
3 AE’s of Statins
Teratogen, Muscle, GI distress, (and neuro)
3 drugs that lower TG and raise HDL
Fibrates, Niacin, Fish Oil
4 potent inhibitors of CYP3A4
Macrolides, CCBs, Azoles, HIV protease inhibitors
Advantage of Pravastatin
Not p450, so fewer interactions
Adverse Effects of Fibrates
GERD, Diarrhea; Fenofibrate increases creatinine, paradoxical HDL lower
AE’s of Niacin besides flushing
Liver, GI, Gout, Eye, Insulin Resistance
Best LDL-lowering class of drugs
Statins
Better tolerated formation of Niacin (nicotinic acid)
ER formulation
Common mechanism of Cholesterol Lowering Drugs
Increase LDL receptors
Contraindications of Bile Acids Seqs
Hyper-TG-emia; Complex regimens, Constipation
Defect in Familial Combined Hyperlipidemia
Overproduction of ApoB (VLDL)
Defect in Familial Dysbetalipoproteinemia
Defective Metabolism of VLDL, Chylomicrons, ApoE defects
Defect in Familial Hypercholesterolemia
LDL receptor, ApoB defect; Decreased receptor-mediated removal of LDL from plasma
Defect in Familial Hypertriglyceridemia
Defective metabolism of VLDL (LPL defect)
Defective metabolism of VLDL (LPL defect)
Defect in Familial Hypertriglyceridemia
Defective Metabolism of VLDL, Chylomicrons, ApoE defects
Defect in Familial Dysbetalipoproteinemia
Defective removal of CM (apoCII, LPL defect)
Defect in Primary Chylomicronemia
Desirable HDL for men
> 40
Desirable HDL for women
> 50
Drug interactions of Bile Acid Seqs
Prevents absorption of other drugs: Digoxin, BB’s, Thyroxine, Coumadin
Drugs that inhibit p-glycoprotein-mediated intestinal reabsorption
Cyclosporine, Grapefruite Juice
Effect of Colestipol on Pancreatitis
May make worse
Effect of Niacin on HDL, LDL, TG
HDL up, LDL down, TG down
Effects of Bile Acid Seqs on LDL, HDL, TG
Dec LDL, Modest HDL, No change or inc. TG!
Effects of N-3 Fatty Acids on TG, HDL, LDL
Reduce TG, Little-no effect on HDL, LDL
Elevated Cholesterol and TG; Plasma has creamy top layer with clear infranate
Primary Chylomicronemia
Gallstones
Fibrates
General MOA of Ezetimibe
Prevents absorption of dietary cholesterol
General MOA of Niacin
Reduces VLDL synthesis
HDL Cholesterol level ranges
High >60 (Desirable: >40 for men, >60 for women)
High Potency Statins
Atorvastatin, Rosuvastatin
How do Bile Acid Sequestrants work
Positively charged, so bind negatively charged bile acids in gut
How do stains increase number of LDL receptors
Promote ER to Golgi transport and cleavage of SREBP-2
How is Ezetimibe used?
Adjunct to Statin, not by itself; or in statin-intolerant patients
If existing heart disease, what type of stains do you want to use
high-intensity: Atorvastatin over Pravastatin, (Rosuvastatin too)
Increased creatinine, paradoxical HDL lowering
Fenofibrate
LDL Cholesterol level ranges
Desirable less than 130, high greater 160
LDL for use of high intensity statin for >21 yo patients
> 190
LDL receptor, ApoB defect; Decreased receptor-mediated removal of LDL from plasma
Defect in Familial Hypercholesterolemia
Lipoprotein effects of Fibrates
VLDL down, HDL up, TG down, LDL unchanged
Main beneficial effects of N-3 Fatty Acids
Reduced plasma TG
Metabolism of Fibrates
Gemfibrozil and Fenofibrate by liver
MOA of Fibrates
Ligand-activation of PPARalpha nulcear receptor
MOA’s of Niacin
Inhibits moblization of FFA from adipocytes; Reduces hepatic TG synthesis and ApoB (VLDL) synthesis
Most common muscle syndrome on statins
Myalgia (10%), no rise in CPK
Overproduction of ApoB (VLDL)
Defect in Familial Combined Hyperlipidemia
PRIMARY tx to reduce risk of recurrent Coronary Disease Events?
Rosuvastatin
Principal dietary components that increase LDL-C
Cholesterol, Saturated and Trans-saturated fats
Promote ER to Golgi transport and cleavage of SREBP-2
How do stains increase number of LDL receptors
Pros of Bile Acid Seqs
Liver Disease OK, Powder and Pill, non-systemic
Statin metabolized by sulfation
Pravastatin
Statins metabolised by CYP3A4
Atorvastatin, Lovastatin, Simvastatin
Statins metabolized by CYP2C9
Fluvastatin, Rosuvastatin
T/F: Adverse effect of Ezetemibe is inhibiting absorption of fat soluble vitamins
FALSE
T/F: Statins are cleared almost completely first-pass?
TRUE
T/F: There are proven CV benefits of adding TG lowering drugs to statins
False, uncertain
TG level ranges
Desirable less than 120, High greater than 200
To Decrease LDL, use
Statins, can add Ezetimibe
To Increase HDL, use
Niacin
Total Cholesterol level ranges
Desirable less than 200, high greater 240
Type of fats that are recommended
Cis-mono unsaturated fats
Unique feature of Niacin
Reduces Lipoprotein(a)
What can limit use of Bile Acid Seqs
GI side effects (bloating, constipation)
What causes GI irritation in Niacin use
Release of Histamine in gut –> Increase gastric acid –> irritation
What does SREBP bind
sterol-regulatory-element 1
What drug causes insulin resistance
Niacin
What is side effect of immediate release niacin
flushing
What is SREBP-2
Binds to sequence in LDL promoter that is sterol-responsive –> transcribe LDL receptor
What should not be used with hx of Peptic Ulcer Disease
Niacin
What type of statin do you use in high risk ASCVD patients
High intensity if under 75, moderate if over
Which class is teratogenic
Statins
Which Fibrate can be given with renal disease
Gemfibrozil
Which Fibrate cannot be given with renal disease
Fenofibrate (renal excretion)
Which fibrate cannot be given with statins and why
Gemfibrozil is metabolized in liver by UGT1A1, same as statins
Which fibrate is excreted by Kidney
Fenofibrate
