Atherosclerosis Pharmacology

Question 1

HMG CoA Reductase Inhibitors

Answer 1

Atorvastatin Lovastatin Simvastatin

Question 2

What is the MOA of the statins?

Answer 2

Decrease production of cholesterol which also increase transcription of LDL-r on the cell which also helps to decrease LDL in the serum

Question 3

How are the statins metabolized?

Answer 3

CYP3A4

Question 4

What is the main side effect with the statins?

Answer 4

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

Question 5

Which polymorphism is associated with statin-induced myopathy?

Answer 5

SLCO1B1

Question 6

In what population are statins contraindicated?

Answer 6

Liver disease Women who are pregnant, lactating or likely to become pregnant

Question 7

Highly positively charged, binds to negatively charged bile acids causing them to be excreted in the stool

Answer 7

Cholestyramine

Question 8

What is the MOA of Cholestyramine?

Answer 8

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.

Question 9

What are some side effects of Cholestyramine?

Answer 9

Constipation/bloating Bad compliance – gritty consistency Modest increase in TGs

Question 10

Water soluble B complex vitamin Main effect to decrease TG but also decreases cholesterol

Answer 10

Nicotinic acid (Niacin)

Question 11

What is Niacin’s MOA?

Answer 11

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

Question 12

What is a main adverse effect of Niacin?

Answer 12

Intense cutaneous flush/pruritus GI, elevated liver enzymes, hyperuricemia, increase fasting glucose

Question 13

What population is Niacin CI in?

Answer 13

Peptic ulcers Gout Hepatic disease Diabetes

Question 14

What is Niacin used for?

Answer 14

Typically not first line for hypercholesterolemia but is used for individuals with hypercholesterolemia and hypertriglyceridemia.

Question 15

Inhibits Niemann pick C10-like protein decreasing the rate of cholesteryl ester incorporation into CM

Answer 15

Ezetimibe

Question 16

What is a side effect of Ezetimibe?

Answer 16

Well-tolerated

Question 17

What is the main use of Ezeimibe?

Answer 17

Primary hypercholesterolemia; combined with statins to further decrease LDL

Question 18

Ligands for nuclear transcription regulator–PPAR (in adipose and liver). Primarily decrease TG.

Answer 18

Gemfibrozil Fenofibrate (2nd gen)

Question 19

How does PPAR gene transcription help with high TG and cholesterol?

Answer 19

Increase LDL particle size Increase HDL synthesis Increase reverse cholesterol transport Decrease inflammation Decrease TG

Question 20

What are some adverse affects of Gemfibrozil and Fenofibrate?

Answer 20

Generally well tolerated GI symptoms most common CI with renal impairment

Question 21

What patient populations are Gemfibrozil and Fenofibrate use in?

Answer 21

Patients with high TG and low HDL with metabolic syndrome or type 2 diabetes Not a primary therapy for hypercholesterolemia w/o increase TG

Question 22

How do omega-3 fatty acids have lipid lowering effects?

Answer 22

Decrease TG Decrease rate of secreted VLDL TG Enhance plaque stability and improve EC function

Question 23

What are some adverse effects of omega-3 fatty acids?

Answer 23

Fish allergy May increase LDL May increase liver enzymes Prolong bleeding time

Question 24

Decreases expression of LDL-r normally

Answer 24

PCSK9 – inhibitors of this as treatment for hypercholesterolemia would increase availability of cell surface LDL-r

Question 25

Transfers neutral lipids between membrane vesicles

Answer 25

MTP (microsomal TG transfer protein)

Question 26

Directly binds to and inhibits MTP; prevents assembly of apo-b containing lipoproteins –> decreases production of CMs and VLDL and subsequently decrease LDL-C

Answer 26

Lomitapide

Question 27

Essential component of LDL-C and VLDL; ligand that binds to LDL-r and is important for transport and removal of atherogenic lipids

Answer 27

Apoprotein B-100

Question 28

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

Answer 28

Mipomersen