Lipid Lowering Drugs

Question 1

Which lipoprotein type contributes to atherosclerosis?

Answer 1

LDL (the most)

probably VLDL also

Question 2

Cholesterol

Answer 2

• cell membranes, membranes of intracellular organelles, hormone synthesis
• primarily manufactured in liver, some dietary intake required

Question 3

Lipoproteins

Answer 3

• transport cholesterol & TGs in blood
• apolipoproteins = recognition sites for cell surface receptors, allows for cellular ingestion & metabolism
• pharm apos = A-I, A-II, B-100

Question 4

VLDL

Answer 4

• TGs as core
• B100
• deliver TGs from liver to adipose & muscle tissue

Question 5

LDL

Answer 5

• cholesterol as core
• B100
• deliver cholesterol from liver to non-hepatic tissue
• increased cellular demand for cholesterol = increased LDL receptor #
• greatest contribution to atherosclerosis

Question 6

HDL

Answer 6

• cholesterol as core
• A-II, A-I
• delivery of cholesterol from peripheral tissues back to liver

Question 7

Which lipoprotein type protects against atherosclerosis

Answer 7

HDL

Question 8

First line treatment for hypercholesterolemia

Answer 8

lifestyle measures

Question 9

which drug class for hypercholesterolemia results in the greatest decrease in LDL

Answer 9

monoclonal antibodies (but not widely used)

**HMG-CoA reductase inhibitors (statins)

Question 10

How do HMG-CoA reductase inhibitors work?

Answer 10

inhibit the enzyme HMG-CoA reductase = increased LDL receptors and increased LDL uptake
–> decreased free LDL

Question 11

PK - HMG CoA reductase inhibitors

Answer 11

PO at night, hepatic met, biliary excretion, Rosuvastatin not well metabolized in Asian heritage

Question 12

HMG-CoA reductase inhibitors

Answer 12

atovastatin, lovastatin, simvastatin, rosuvastatin

Question 13

Adverse effects of HMG-CoA reductase inhibitors

Answer 13

myopathies (can lead to rhabdomyolysis)
hepatotoxicity

Question 14

Bile acid sequestrants

Answer 14

colesevelam, cholestyramine, colestipol

Question 15

mechanism of action of bile acid sequestrants

Answer 15

• remain in GI tract and bind up bile acids –> decreased absorption/increased excretion
• increases hepatocyte LDL receptor #

Question 16

adverse effects of bile acid sequestrants

Answer 16

GI side effects (i.e. constipation)

Question 17

Fibric acid derivatives / fibrates

Answer 17

gemfibrozil, fenofibrate, bezafibrate

Question 18

mechanism of action of fibrates

Answer 18

inhibit hepatic production of triglycerides - decreased VLDL
(i.e. NOT LDL which holds cholesterol)

Question 19

adverse effects of fibrates?

Answer 19

GI disturbances
gallstones
myopathy
hepatotoxicity

Question 20

mechanism of action of ezetimibe

Answer 20

decreased dietary & biliary cholesterol absorption/reabsorption

Question 21

PK: ezetimibe

Answer 21

PO, converted to active metabolite esetimibe glucuronide, biliary elimination

Question 22

adverse effects of ezetimibe

Answer 22

myopathy/rhabdomyolysis
hepatitis
pancreatitis
thrombocytopenia

Question 23

PCSK9 inhibitors

Answer 23

alirocumab, evolocumab

Question 24

mechanism of action of monoclonal antibody (PCSK) inhibitors

Answer 24

inhibit PCSK9
PCSK9 usually binds LDL receptors in liver

free LDL receptors = increased LDL uptake & less free LDL

Question 25

adverse effects of monoclonal antibody (PCSK9) inhibitors

Answer 25

hypersensitivity immunogenicity

Question 26

PCSK9 inhibitors: PK

Answer 26

subQ, dosing Q2 weeks, 11-20 day 1/2 life; used in combination w/ statins in patients w/ high risk of mortality / morbidity

Question 27

ACL inhibitors

Answer 27

Bempedoic acid

Question 28

mechanism of action of ACL inhbitors

Answer 28

inhibit ACL activity (enzyme higher up pathway than HMG-CoA) --> increased LDL receptor & increased uptake of LDL, decreased cholesterol synthesis

Question 29

adverse effects of ACL inhibitors

Answer 29

increased uric acid (gout risk) tendon rupture

Question 30

When & how should patients take their HMG-CoA Reductase inhibitor medication

Answer 30

at night, PO

Question 31

list some HMG-CoA Reductase inhibitors

Answer 31

"statins" atorvastatin lovastatin simvastatin rosuvastatin

Question 32

s/s of myopathy that can lead to rhabdo with statin administration

Answer 32

muscle aches tenderness weakness

Question 33

What is the risk if patient doesn't call provider w/ myopathies?

Answer 33

progression to myositis with increased CK & K+ can lead to renal injury

Question 34

What labs do we monitor upon initial therapy with HMG-CoA reductase inhibitors?

Answer 34

CK at start of therapy and again if symptomatic

Question 35

Name some bile acid sequestrants

Answer 35

colesevelam cholestyramine colestipol

Question 36

Name some fibric acid derivatives

Answer 36

gemfibrozil fenofibrate bezafibrate