Anti-Lipid Drugs Flashcards
Which of these classes of drugs does NOT work by lowering serum LDL?
a. statins
b. bile acid-binding resins
c. NPC1L1 inhibitors
d. PCSK9 inhibitors
e. ACL inhibitors
f. fibril acid derivatives
lower serum LDL:
a. statins (Atorvastatin, Lovastatin)
b. bile acid-binding resins (Colesevelam)
c. NPC1L1 inhibitors (Ezetimibe)
d. PCSK9 inhibitors (Alirocumab)
e. ACL inhibitors (Bempedoic Acid)
lower septum TAG and raise HDL:
f. fibril acid derivatives (Gemfibrozil)
[also vit. B3 (Niacin)]
atorvastatin vs lovastatin
high potency statins: atorvastatin, rosuvastatin, simvastatin
low potency statins: lovastatin, pravastatin, fluvastatin, pitavastatin
recall statins inhibit HMG CoA reductase (lower LDL), also cause modest increase in serum HDL
how to atorvastatin and lovastatin work?
statins = HMG CoA reductase competitive inhibitors
rate-limiting enzyme in hepatic cholesterol biosynthesis —> increased expression of LDL receptor = lower plasma LDL (and IDL)
atorvastatin = high potency statin
lovastatin = low potency statin
Statins are considered first-line LDL-lowering agents; however, patients with this condition will not respond as well. What is?
homozygous familial hypercholesterolemia - due to both alleles of LDL receptor being dysfunctional
what are the 2 adverse reactions associated with statins?
- myopathy (muscle issues) - rarely rhabdomyolysis (elevated creatinine kinase)
- hepatotoxicity - will see modest elevation in liver enzymes
what is the mechanism of action of colesevelam, cholestyramine, and colestipol?
bile acid-binding resins (sequestrant): large cationic polymer that binds anionic build acids in intestinal lumen, preventing reabsorption
—> bile acid elimination drives more bile acid synthesis in liver —> this requires cholesterol synthesis —> unregulated LDL receptors lower plasma LDL/IDL levels
*note resin-induced decrease in hepatic cholesterol is slightly offset by increase in HMG CoA reductase activity - therefore work best in combination with statins
when is colesevelam, cholestyramine, or colestipol use indicated?
bile acid-binding resin (sequestrant): resin-induced decrease in hepatic cholesterol is partially offset by up-regulation of HMG CoA reductase
therefore, work best in combination with statins - most often used in patients requiring additional lowering of atherogenic cholesterol (start with lowest dose, escalate slowly as tolerated/needed)
what adverse reactions are associated with colesevelam, cholestyramine, and colestipol?
bile acid-binding resins
adverse effects are limited to GI tract since resins are not absorbed: dyspepsia, constipation, bloating, flatulence
*not recommended for patients with high TAGs since increased bile acid production is accompanied by modest increase in hepatic TAG synthesis
what is the mechanism of action of Ezetimibe?
Ezetimibe: inhibits NPC1L1 enterocyte cholesterol transporter —> reduced absorption of dietary cholesterol
—> less cholesterol is delivered to liver —> LDL receptor up-regulation —> further lowered serum LDL
works synergistically with statins
bile acid-resins are _____ to statin efficacy, while Ezetimibe is _____ to statin efficacy
bile acid-resins are ADDITIVE to statin efficacy, while Ezetimibe (NPC1L1 inhibitor) is SYNERGISTIC to statin efficacy
When is Ezetimibe use implicated?
Ezetimibe: inhibits NPC1L1 enterocyte cholesterol transporter
works synergistically with statins - main use is in combination with statins (when high potency is not enough) or in patients who can’t tolerate statins
no significant adverse effects
what is the mechanism of action of alirocumab and evolocumab?
PCSK9 inhibitors (mAb) —> increased LDL receptors —> lower serum LDL
recall PCSK9 protease binds hepatocyte LDL receptor and enhances its degradation
when is use of alirocumab or evolocumab implicated?
PCSK9 (enhances LDL receptor degradation) inhibitor (mAb - monoclonal antibodies)
biologics are never first-line because they can’t be given orally and commonly cause injection site reactions
approved for patients with heterozygous familial hypercholesterolemia who don’t respond well to statins alone
what is the mechanism of action of bempedoic acid in lowering serum LDL?
bempedoic acid: competitively inhibits hepatic ATP-citrate lyase (ACL), which is upstream of HMG CoA reductase (rate-limiting step) in cholesterol synthesis
ACL is required for generating acetyl-CoA needed for de novo cholesterol synthesis (the building blocks)
—> up-regulated LDL receptor —> lower serum LDL
when is bempedoic acid use implicated?
bempedoic acid: competitively inhibits hepatic ATP-citrate lyase (ACL), required for generating acetyl-CoA (building blocks of cholesterol synthesis)
LDL lowering activity is additive with statins and ezetimibe (NPC1L1 inhibitor)
approved for oral use in patients with heterozygous familial hypercholesterolemia for which max statin therapy alone is not enough to lower LDL
