Anti-lipid drugs Flashcards
HMG CoA reductase inhibitors have what functions?
- Block synthesis of cholesterol
- INCREASE uptake of LDL into hepatocytes via LDL-receptor
What are some other HMG CoA reductase inhibitor functions?
- Increase endothelial NO and vasorelaxation
- Stabilize arterial plaques, and reduce risk of thrombosis
- Reduce inflammation in atherogenesis
* 4. Reduce Platelet activation and risk of VTE (43% reduction)*
Some statins should only be taken at night, why is that so?
Because liver synthesis peaks between midnight and 2am
Which statins should be taken at night?
lovastatin, simvastatin, fluvastatin
Which statins can be taken anytime?
atorvastatin, rosuvastatin, and pravastatin
What are some toxicities of statins?
Birth defects (class X), hepatotoxicity (particularly in patients with underlying disease or chronic alcohol use), myopathy (low baseline risk but increases with dose, age, hepatic and renal function, and other drug interactions). Myopathy can progress to rhabdomyolosis
Phase 1 CYP2C19 metabolizes which statins?
Fluvastatin and rosuvastatin
Phase 1 CYP3A4 metabolizes which statins?
Lovastatin, simvastatin, and atorvastatin
Phase 2 sulfation metabolizes which statin?
pravastatin
What are some drugs that inhibit CYP3A4 and therefore increase risk of myopathy with concomittant use of statins?
Gemfibrozil (anticholesterol), amlodipine, warfarin, macrolides, azoles, digoxin, cyclosporin
Simvastatin dose should not exceed what amount with amlodipine?
20mg/day
Bile acid binding agents help decrease cholesterol by what mechanism?
They increase elimination of bile acids, drawing more cholesterol out of liver and eliminates them rather than being reabsorbed as cholesterol
True or false: Colestipol enters the blood stream
False, it only remains in the GI tract
BABA drugs are a decent alternate to what drug class during pregnancy
statins, but can be used alongside with statins
What are some issues with BABA drugs?
- They have high doses (grams) which can lead to GI toxicities like dyspepsia, flatulence/bloating, diarrhea/constipation
- They also reduce absorption of numerous other drugs
When should you take your medications while on BABA agents?
1 hour before or 3 hours after BABA administration
Statins and BABA agents together can bring LDL down by what percent?
40-60%
Statins have what effect on LDL, TG, and HDL
Decreases LDL and TG; no effect on HDL
BABA agents have what effect on LDL, TG, and HDL
Decreases LDL, No effect on TG, Increases HDL minimally
True or false: daily vitamins of niacin provide adequate amount
False, they provide little niacin
What is the mechanism of action of Niacin?
Inhibits the synthesis of TGs in the liver
What are the toxicities of Niacin?
Common, not serious: Flushing/pruitis
Serious, not common: Hepatotoxicity, insulin resistance (use cautiously in DM)
Niacin has what effect on LDL, TG, and HDL
Decreases LDL and TG. Increases HDL (does more so than others)
Fibric acid derivatives have what mechanisms of action in lowering cholesterol?
- Increases LDL receptor expression in hepatocytes, promoting sucking up of free cholesterol
- Activate Lipoprotein Lipase, therefore breaking down TGs
- Promotes oxidation of FFAs downstream
What are some Fibric Acid toxicities/drug interactions?
- Myopathy (5%) when used with statins as fibric acid deriviatives Inhibit statin absorption into liver leading to increased serum statin and potentially myopathy
- Fibric acid derivatives bind to albumin and when used concomitantly with warfarin, warfarin can get kicked off albumin leading to free warfarin in blood increasing bleeding risk
Fibric acid derivatives have what effects on LDL, TG, and HDL
Decreases LDL (but is variable on type of dyslipidemia), Decreases TG, and Increases HDL
Ezetimibe has what mechanism of action when it comes to cholesterol?
Blocks absorption of cholesterol from intestines (NPC1 cholesterol receptor inhibitor) and therefore stimulates LDL-R expression
Inhibition of ezetimibe increases synthesis of cholesterol, however. What drug can be combined with ezetimibe to inhibit this production?
Statins
Ezetimibe has what effects on LDL, TG, and HDL
Decreases LDL, No effect on TG and HDL
Alirocumab and Evolocumab have what mechanism of action when it comes to cholesterol?
They are antibody drugs that inhibit PCSK9. PCSK9 is a protein that induces LDL-R degradation. These antibody drugs therefore increase number of LDL-R on hepatocytes
PCSK9 inhibitors have what effect on LDL, TG, and HDL
Decrease LDL. No effect on TG or HDL
