Antihyperlipidemics

Question 1

Lipid digestion products associate with bile salts to form ______ (transport poorly soluble products to surface of enterocyte)

Answer 1

micelles

Question 2

what is choelsterol absorbed thruogh

Monoglycerides and fatty acids diffuse across plasma membrane

Answer 2

NPC1L1 (Niemann-Pick C1 like 1) transporter

Question 3

synthesis of chylomicrons (exogenous metabolism)

Answer 3

1. SI mucosal cells secrete TAG-rich chylomicrons
2. Apo C-ll and E are transferred from HDL to nascent chylomicron
3. chylomicron –> systemic circulation
4. Lipoprotein lipase (Apo C-II activates it) degrades TAG in CM in capillaries –> FA to tissues and glycerol to liver
5. Apo E is receptor on liver that allows take up of chylomicron remnants

Question 4

Endogenous synthesis/metabolism of VLDL, IDL, LDL

Answer 4

1. Apo B attachd to Tag-rich VLDL particles in liver
2. secretes and Apo C-II and E are added to VLDL
3. VLDL enters capillaries and lipoprotein lipase degrades –> FA to tissues and glycerol to liver –> IDL –> LDL
   (can be converted to LDL or taken up by liver)
4. LDL binds to receptors on extrahepatic tissue

Question 5

what is apoE important for

Answer 5

important for chylomicron elemetns to be taken up and LDL

Question 6

How is excess cholesterol gotten rid of

Answer 6

HDL takes it up

HDL binds to A-1 and SR-BI in liver

Question 7

what apolipoprotein is ligand for LDL

what happens if inactivated

Answer 7

Apo B-100

increase in LDL

Question 8

what apolipoprotein is cofactor for LPL

what happens if inactivated

Answer 8

Apo C-II

increase chylomicrons and VLDL

Question 9

what apolipoprotein is Ligand for IDL to bind to LDL receptor and chylomicron remnants to bind to remnant receptors

what happens if inactivated

Answer 9

ApoE

increase IDL and chylomicrons

Question 10

what happens if LPL is inactivated

Answer 10

increase in chylomicrons and VLDL

Question 11

what happens if LDL-receptor is inactivated

Answer 11

increase LDL

Question 12

what are the statins target?

Answer 12

HMG CoA reductase inhibitors

Question 13

what are the fibrates (PPAR activators)?

Answer 13

gemfibrozil

fenofibrate

Question 14

what are the bile acid sequestrants

Answer 14

Colesevelam

Colestipol

Cholestyramine

Question 15

what is a cholesterol absorption inhibitor

Answer 15

Ezetimibe

Question 16

what is fibric acid derivatives used to treat

Answer 16

hypertriglyceridemia

Question 17

adverse effects of fibrates

Answer 17

Rarely cause rashes, gastrointestinal symptoms, and myopathy

Risk of myopathy increases with combination with statins

Question 18

Gemfibrozil is contraindicated with what drug

Answer 18

statins

Use caution when combining fenofibrate with statins

Question 19

what do bile acid-binding resins treat

Answer 19

hypercholesterolemia - for patients whom statins do not provide sufficient LDL reduction

Question 20

MOA of bile acid-binding resins

Answer 20

***Bind to bile acids and bile salts in intestine

Disrupt enterohepatic circulation of bile acid and bile salts

Liver has to increase synthesis of bile acid to replace lost bile acids and salts

Requires increased liver uptake of cholesterol
Elevation of liver LDL-receptors

Question 21

MOA of fibrates

Answer 21

activates PPAR receptor

Question 22

Bile acid-binding resins:

↓ 1
However, can increase plasma 2
Should not generally be used in patients with 3
Can cause 4 and constipation

Answer 22

1. LDL
2. TG
3. hypertriglyceridemia
4. bloating

Question 23

Drug of choice to lower cholesterol in children and women who are pregnant or lactating
(not systemically absorbed)

Answer 23

Bile acid-binding resins

Question 24

MOA of niacin

Answer 24

Inhibit VLDL synthesis & secretion by liver

Question 25

what does niacin treat

Answer 25

Can be useful in treatment of all hypertriglyceridemias and hypercholesterolemia

Question 26

SE of niacin

Answer 26

Cutaneous flushing and itching (most common side effect) - due to prostacyclin from skin released - pretreat with NSAID Hyperuricemia (induce gout attacks in susceptible individuals) Hepatotoxicity (slight risk) Slightly increases risk of statin-induced myopathy Safest combination is niacin with fluvastatin and highest risk is with lovastatin

Question 27

what is the safest combo for niacin and a statin to decrease risk of statin-induced myopathy what is the highest risk combo

Answer 27

niacin with fluvastatin highest risk = lovastatin

Question 28

what drug inhibits cholesterol absorption at jejunum

Answer 28

Ezetimibe

Question 29

Ezetimibe (Zetia) blocks intestinal absorption of cholesterol by inhibiting ___

Answer 29

*** Niemann-Pick C1-like 1 protein Blocks uptake of both dietary cholesterol and reabsorption of cholesterol excreted in bile Reduces incorporation of cholesterol into chylomicrons Reduced chylomicron remnants delivered to liver increases expression of hepatic LDL receptors Reduces plasma LDL levels by 15-20%

Question 30

What can ezetimibe tx

Answer 30

hypercholesterolemia

Question 31

what statin is least potent and what are most potent

Answer 31

Least: Fluvastatin Most: atorvastin and rosuvastatin

Question 32

MOA of statins

Answer 32

**inhbit HMG CoA reductase --> decrease concentration of cholesterol in cells low cholesterol --> stimulates synthesis of LDL receptros --> uptake of LDL from blood low intracellular cholesterol decreases VLDL

Question 33

what drugs greatly reduce CV risk and mortality

Answer 33

statins

Question 34

SE of statins

Answer 34

Myopathy - Patients with an inherited variant in a anion transporter are at higher risk for myopathy - Baseline creatine kinase measurements recommended Rarely rhabdomyolysis occurs *Liver toxicity in low percentage of patients

Question 35

clinical indictions for statins

Answer 35

Indications Elevated LDL, CVD, and elevated CVD risk Used to lower plasma cholesterol levels in many types of hyperlipidemias Given to patients with clinically evident atherosclerotic disease or at high risk

Question 36

first line tx of hypercholesterolemia if pts do not respond adequately then what?

Answer 36

Statins Add cholesterol absorption inhibitors and/or bile acid binding resins

Question 37

what is niacin often useful for

Answer 37

both hypercholesterolemia and hypertriglyceridemia

Question 38

what is often used for Hypertriglyceridemia (generally elevated VLDL and/or chylomicrons)

Answer 38

fibrates Niacin