Pharm - Cholesterol

Question 1

Drugs that are primarily used to lower cholesterol

Answer 1

Statins
Ezetimibe 
Resins
PCSK9 inhibitors
ApoB antisense
MTP inhibitor

Question 2

Drugs that are primarily used to lower triglycerides

Answer 2

Fibrates

Question 3

Drugs that are primarily used to lower both cholesterol and triglycerides

Answer 3

Niacin

Question 4

Drugs to lower LDL cholesterol:
Statins
MOA

Answer 4

• Inhibit biosynthesis
• Induce LDL receptors to increase removal of LDL
• binds to HMG CoA reductase

Question 5

1st line drugs for both primary and secondary prevention of ASCVD

Answer 5

Statins

-monotherapy or combined with resins or ezetimibe

Question 6

What is the most potent statin?

Answer 6

Rosuvastatin

Question 7

Adverse effects of statins

Answer 7

Mild GI disturbances
Reversible memory loss
Headache
Rash
Diabetes
***Myopathy (common)
Rhabdomyolysis (rare)

Question 8

Contraindications for statins

Answer 8

Pregnant and lactating women

Serious illness, trauma, major surgery, or liver disease

Question 9

Drug-drug interactions of statins

Answer 9

Any drug that affects
CYP3A4 (lovastatin, simvastatin, atorvastatin) or
CYP2C9 (fluvastatin, rosuvastatin)

Question 10

Ezetimibe

MOA

Answer 10

• Inhibits intestinal sterol absorption (NPC1L1)

- inhibits expression of hepatic LDL receptors

Question 11

For patients who can’t tolerate statins

For primary and secondary preventions of ASCVD

Answer 11

Ezetimibe

Question 12

Resins

MOA

Answer 12

Increase bile acid excretion
induce up regulation of LDL receptors

*not absorbed orally

Question 13

Resins:

Examples

Answer 13

Colestipol
Cholestyramine
Colesevelam

Question 14

Primary and secondary prevention of ASCVD
antitoxic agents for cardiac glycosides
Bile malabsorption caused diarrhea

Answer 14

Resins

Question 15

___ can be used to treat hyperlipidemia in pregnant women

Answer 15

Resins

Question 16

Side effects of resins

Answer 16

Relatively safe
Constipation and bloating
Increase VLDL

Question 17

Side effects of ezetimibe

Answer 17

Few

Question 18

Contraindications for resins

Answer 18

Diverticulitis

Elevated VLDL

Question 19

Drug-drug interactions for resins

Answer 19

Absorption of some oral drugs may be reduced

Question 20

PCSK9 inhibitors

Examples

Answer 20

“Proprotein convertase subtilisin hexin 9”

• alirocumab
• evilocumab

Question 21

Used as an adjunct to diet and maximally tolerated statin in patients with HeFH when require additional lowering of LDL cholesterol

Answer 21

PCSK9 inhibitors

Question 22

Side effects of PCSK9 inhibitors

Answer 22

Injection site reaction

Myalgia

Question 23

Standard treatment for HoFH (homozygous familial hypercholesterolemia)

Answer 23

• low fat diet, high dose statin
• ezetimibe
• bile acid sequestrants
• niacin
• LDL apheresis

Question 24

2 orphan drugs for HoFH

Answer 24

Mipomerson

Lomitapide

Question 25

Adverse effects of Mipomerson and Lomitapide

Answer 25

- both: Liver toxicity (transaminase elevations and hepatic steatosis) - lomitapide: GI side effects - mipomerson: injection site rxns

Question 26

MOA 1. Mipomerson 2. Lomitapide

Answer 26

1. Binds to apoB to decrease expression 2. Binds to MTP to inhibit it * both inhibit synthesis

Question 27

Drug-drug interactions for lomitapide

Answer 27

CYP3A4 inhibitors | P-glycoprotein substrates

Question 28

Major contraindications for lomitapide and mipomerson

Answer 28

Hepatic diseases | *lomitapide: pregnant and lactating women

Question 29

Fibrates | MOA

Answer 29

Bind to PPAR alpha - increase LDL expression, increases lipolysis of triglycerides, lowers VLDL - oxidizes FFA, lowers VLDL synthesis - increases apoA1 expression, increases HDL

Question 30

Fibrates examples

Answer 30

Gemfibrozil | Fenofibrate

Question 31

Drug of choice for hypertriglyceridemia

Answer 31

Fibrates

Question 32

Adverse effects of fibrates

Answer 32

Rare Rashes GI effects *risk of myopathy and rhabdomyolysis increases when used with statins

Question 33

Contraindications for fibrates

Answer 33

Hepatic dysfunction | Renal dysfunction

Question 34

Drug-drug interactions for fibrates

Answer 34

- gemfibrozil: myopathy with statins - fenofibrate: nephrotoxic drugs * both can potentiate the anticoagulation effects of warfarin and the antihyperglyceremic effects of pioglitazone

Question 35

Drugs used to lower LDL and VLDL Nicotinic acid MOA

Answer 35

* niacin, vitamin B3 - reduces Lp(a) - increases HDL and tPA

Question 36

Uses of nicotinic acids

Answer 36

Hypercholesterolemia by combining with resins and statins | Hypertriglyceridemia

Question 37

Adverse effects of nicotinic acids

Answer 37

Flush (PGE2 and PGD2) and dyspepsia | -high dose=GI distress, liver dysfunction, insulin resistance, hypotension, hyperuricemia

Question 38

Contraindications of nicotinic acids

Answer 38

Hepatic dysfunction and active peptic ulcer

Question 39

True or false: if one statin is not working well enough we should add another statin

Answer 39

False | Never!

Question 40

Which statins are prodrugs?

Answer 40

Lovastatin | Simvastatin

Question 41

Statins are analogues of ___and inhibit ___

Answer 41

HMG-CoA HMG-CoA Reductase *rate limiting step of synthesis

Question 42

Medications that inhibit CYP3A4 or CYP2C9 can ____ statins concentrations, while medications that induce them ____ statins concentrations

Answer 42

Increase | Decrease

Question 43

____ is the first drug that inhibits intestinal absorption of cholesterol. It is absorbed and conjugated in the intestine to an active glucuronide

Answer 43

Ezetimibe

Question 44

Ezetimibe's duration of action is ___

Answer 44

Long | 22 hour half life

Question 45

____ binds to NPC1L1 on GI epithelial cells to reduce absorption. What else does this drug do?

Answer 45

Ezetimibe | Increases expression of hepatic LDL receptors thus promoting uptake

Question 46

Examples of resins:

Answer 46

Colestipol Cholestyramine Colesevelam

Question 47

Resins enhance the conversion of cholesterol to ____ | They also do what?

Answer 47

Bile acids in the liver by 7 alpha hydroxylation and increasing excretion from feces *also induce up regulation of LDL receptors

Question 48

___ can be used for pregnant women with hyperlipidemia | What else can they be used for?

Answer 48

Resins | Digitalis toxicity

Question 49

PCSK9 inhibitors are human monoclonal antibodies that prevent PCSK9 from binding to ___

Answer 49

LDL receptors and degradation of LDL receptors thus increasing hepatic uptake and metabolism of LDL-C

Question 50

___ are given subcutaneously once every two weeks or every month

Answer 50

PCSK9 inhibitors

Question 51

Apo B-100 synthesis inhibitors are used to treat ___

Answer 51

Homozygous familial hypercholesterolemia

Question 52

___ binds to and cleaves apoB mRNA in the nucleus of hepatocytes, which inhibits apoB protein leading to reduced production of VLDL and LDL

Answer 52

Mipomersen

Question 53

Administration route of mipomersen

Answer 53

Subcutaneous injections once a week

Question 54

Administration route of Lomitapide | Metabolism

Answer 54

Orally once a day | CYP3A4

Question 55

True or false: | Mipomersen has no interactions with simvastatin from, ezetimibe, or warfarin

Answer 55

True

Question 56

Fibrates decrease VLDL by ___

Answer 56

1. Increase LPL expression 2. Reducing synthesis of VLDL 3. Increasing HDL

Question 57

True or false: fibrates do not pass the placenta

Answer 57

False. They easily pass it

Question 58

___ is the most effect be agent for increasing HDL and is the only agent for reducing Lp(a)

Answer 58

Niacin

Question 59

These drugs lower LDL

Answer 59

``` Statins Resins Ezetimibe PCSK9 inhibitors ApoB antisense MTP inhibitor Nicotinic acid ```

Question 60

These drugs lower VLDL

Answer 60

Fibrates Omega 3 PUFAs Nicotinic acid

Question 61

___ acts as a PPAR alpha agonist to lower trigs

Answer 61

Gemfibrozil