L 6/7 Anti-Hyperlipidemics Flashcards
What is Hyperlipidemia?
Excess lipids in the blood
Cholesterol plaque formation is the underlying cause of which conditions?
Angina, MI, Atherosclerosis, Hypertension, Heart Failure
Cholesterol Synthesis occurs through which pathway?
Mevalonate Pathway
Which enzyme catalyzes the rate limiting step of the Cholesterol Synthesis Pathway?
HMG-CoA Reductase (HMGCR)
Statin drugs all end with ______?
-statin
Statin MOA (Primary):
-Inhibits HMGCR enzyme in Mevalonate Pathway. (Selective competitive inhibition)
-Blocks cholesterol synthesis
-Reduces Cholesterol
Statin MOA (Secondary):
SREBP, in ER and Golgi, senses decreased cholesterol and gets cleaved and translocated into nucleus. LDL Receptor gene turned on to increase LDL receptors on every cell to breakdown LDL and make new cholesterol.
-Decrease LDL
Which two statins are inactive precursors?
Simvastatin and Lovastatin.
Converted to Beta-hydroxy acid derivatives.
-Simvastatin Hydroxy Acid (SVA)
-Lovastatin Hydroxy Acid (LVA)
Statin First Pass Metabolism is regulated by:
Organic Anion Transporter (OAT1B1)
Statin Adverse Effects:
- Hepatotoxicity ( increased AST, ALT)
- Myopathy: Should supplement with Co-Enzyme Q10
- Rhabdomyolysis (rapid muscle damage, rare): risk increases with Grapefruit drug-food interaction (furanocoumarins inhibit CYP enzymes, increases hepatotoxicity).
Bile Acid Sequestrant Drug names all start with ______.
Cole-/Chole-
Bile Acid Sequestrants MOA:
Are resins (positively charged) that bind bile acids (negatively charged). The complex is easily excreted from body.
- Decreases Bile Acids
- Induces production of more bile acids, using cholesterol.
-Decreases Hepatic Cholesterol
-Increased LDL receptor expression
Bile Acid Sequestrants Adverse Effects
Hypertriglyceremia
-must monitor triglycerides
GI issues:
-Bloating
-Dyspepsia
-Constipation
Bile Acid Sequestrant Contraindications:
High Triglycerides
Also, resins bind to other drugs and prevents absorption. Take this drug at least a few hours before or after other drugs.
Niacin MOA:
( Acts on Niacin receptor 1/2 (GPCR Family) )
-Inhibits HSL (Hormone Sensitive Lipase) in Adipose tissue. Prevents TG breakdown into FFAs.
-Decreased FFAs prevents liver from making TG to form VLDLs
-Results in Decreased TG and LDL, and increased HDL
-Niacin also increases LPL activity: Increases clearance of VLDLs and Chylomicrons
-Increases Apo A (HDL)
-Enhances Efflux of cholesterol from monocytes and macrophages (good)
Niacin Adverse Effects
-Flushing: increased by caffeine or ethanol
-Hepatotoxicity (important)
-Hyperglycemia (from liver)