HMG CoA Reductase Inhibitors
Atorvastatin Lovastatin Simvastatin
What is the MOA of the statins?
Decrease production of cholesterol which also increase transcription of LDL-r on the cell which also helps to decrease LDL in the serum
How are the statins metabolized?
What is the main side effect with the statins?
Myopathy: muscle pain without CK elevation (possible d/t depletion of secondary metabolic intermediates) Rhabdomyolysis: muscle symptoms with increased CK d/t the breakdown of muscle fibers
Which polymorphism is associated with statin-induced myopathy?
In what population are statins contraindicated?
Liver disease Women who are pregnant, lactating or likely to become pregnant
Highly positively charged, binds to negatively charged bile acids causing them to be excreted in the stool
What is the MOA of Cholestyramine?
It decreases the pool of bile acids (increasing excretion) which causes more production of bile acids from cholesterol. This decreases hepatic cholesterol and stimulates LDL-r through SREBP TF.
What are some side effects of Cholestyramine?
Constipation/bloating Bad compliance -- gritty consistency Modest increase in TGs
Water soluble B complex vitamin Main effect to decrease TG but also decreases cholesterol
Nicotinic acid (Niacin)
What is Niacin's MOA?
In adipose -- inhibits FFA mobilization In liver -- decreases synthesis of VLDL by inhibiting DGAT2 and inhibits catabolism of HDL by inhibiting it's uptake through apoA1
What is a main adverse effect of Niacin?
Intense cutaneous flush/pruritus GI, elevated liver enzymes, hyperuricemia, increase fasting glucose
What population is Niacin CI in?
Peptic ulcers Gout Hepatic disease Diabetes
What is Niacin used for?
Typically not first line for hypercholesterolemia but is used for individuals with hypercholesterolemia and hypertriglyceridemia.
Inhibits Niemann pick C10-like protein decreasing the rate of cholesteryl ester incorporation into CM
What is a side effect of Ezetimibe?
What is the main use of Ezeimibe?
Primary hypercholesterolemia; combined with statins to further decrease LDL
Ligands for nuclear transcription regulator--PPAR (in adipose and liver). Primarily decrease TG.
Gemfibrozil Fenofibrate (2nd gen)
How does PPAR gene transcription help with high TG and cholesterol?
Increase LDL particle size Increase HDL synthesis Increase reverse cholesterol transport Decrease inflammation Decrease TG
What are some adverse affects of Gemfibrozil and Fenofibrate?
Generally well tolerated GI symptoms most common CI with renal impairment
What patient populations are Gemfibrozil and Fenofibrate use in?
Patients with high TG and low HDL with metabolic syndrome or type 2 diabetes Not a primary therapy for hypercholesterolemia w/o increase TG
How do omega-3 fatty acids have lipid lowering effects?
Decrease TG Decrease rate of secreted VLDL TG Enhance plaque stability and improve EC function
What are some adverse effects of omega-3 fatty acids?
Fish allergy May increase LDL May increase liver enzymes Prolong bleeding time
Decreases expression of LDL-r normally
PCSK9 -- inhibitors of this as treatment for hypercholesterolemia would increase availability of cell surface LDL-r
Transfers neutral lipids between membrane vesicles
MTP (microsomal TG transfer protein)
Directly binds to and inhibits MTP; prevents assembly of apo-b containing lipoproteins --> decreases production of CMs and VLDL and subsequently decrease LDL-C
Essential component of LDL-C and VLDL; ligand that binds to LDL-r and is important for transport and removal of atherogenic lipids
Antisense oligonucleotide to inhibit synthesis of apoB-100 in the liver; lipid lowering effects last almost 3 months after subq dose. Treatment for familial hypercholesterolemia