Hyperlipidemia Treatment

Question 1

How do Statins (HMG-CoA reductase inhibitors) work?

Answer 1

They limit the rate limiting step of cholesterol synthesis. They also upregulate LDL receptors in the liver (SREBP channels). Reduce lipoprotein secretion by the liver.

Question 2

What is the effect of statins?

Answer 2

Lower LDL up to 60%, Lower TG by 37%, increase HDL

Question 3

What are the major drug interactions for statins

Answer 3

Drugs that inhibit CYP3A4
Drugs that inhibit P-glycoprotein mediated intestinal reabsorption (cyclosporine and grapefruit juice), drugs that inhibit other pathways involved in statin metabolism.

Question 4

Why do statins have such a low bioawvailabilty?

Answer 4

Because they are so heavily reabsorbed in the small intestine by p-glycoprotein

Question 5

Adverse Effects of Statins

Answer 5

mild GI distress and others. pretty well tolerated
Statin use with Gemfibrozil leads to Rhabdomyolysis

Question 6

WHat do Bile Acids do?

Answer 6

Interrupt enterohepatic recycling of cholesterol by binding negatively charged bile acids in the gut

Question 7

What are the advantages of Bile Acid sequestrants?

Answer 7

Old and safe, safely used in children and people with liver disease

Question 8

What effect do bile acid sequestrants have on cholesterol levels

Answer 8

Lowers LDL by 25%…not as effective as Statins

Question 9

Bile Acid Sequestrants adverse effects

Answer 9

GI upset - bloating, farting, constipation
Prevents absorption of other drugs

Question 10

Cholesterol Absorption Inhibitors prototype drug

Answer 10

Ezetimibe

Question 11

How does Ezetimibe work>

Answer 11

prevents intestinal uptake of cholesterol itself whereas bile acids prevent re-uptake of bile acids

Question 12

Does Ezetimibe have an effect on the plasma levels of vitamins ADEK?

Answer 12

no

Question 13

Ezetimibe drug interactions

Answer 13

Bile acid sequestrants decrease the absorption of ezetimibe up to 80% (do not co-administer)

Cyclosporine increases ezetimible levels

Question 14

Fibric Acid Derivatives do what?

Answer 14

Reduce VLDL and triglycerides and raise HDL

Question 15

Lipoproteins

Answer 15

Macromolecular complexes in the blood that transport lipids

Question 16

Atorvastatin Metabolized how and where?

Answer 16

CYP3A4, beta oxidation, hydroxylation.
Fecal excretion

Question 17

Why do you have to reduce the dose of statins in those with liver disease

Answer 17

Because some statins, like provaststin are excreted renally

Question 18

Atorvastatin, simvastatin, and lovastatin should not be given with what drugs

Answer 18

Drugs that inhbit CYP3A4 like macrolide antibiotics (mycins), azole antifungals, selected SSRIs, calcium channel blockers, HIV protease inhibitors (-avirs), Immunosuppresants like cyclosporine.

Question 19

Gemfibrozil given with a statin

Answer 19

equals rhabdomyolysis

Question 20

Bile Acid Sequestrants prevent absorption of what other drugs

Answer 20

Beta Blockers, Digoxin, Thyroxine, Coumadin

Question 21

Bile acid sequestrants side effects

Answer 21

Constipations, farting, fecal impaction

Question 22

Bile Acid sequestrants contraindicated in who?

Answer 22

Old constipated ppl, those with complex drug regimens, those with hypertriglyceridemia

Question 23

Ezetimibe

Answer 23

inhibts cholesterol absorption by small intestine, no effect on fat soluble vitamins ADEK, reduces cholesterol delivery to the liver which in turn causes LDL receptors to be upregulated

Question 24

What should you not give Ezetimibe with

Answer 24

Bile acid sequestrants, they reduce ezetimibe absorption by 80%
Cyclosporine increases ezetimibe levels 3-4 fold
Fibrates: increase the risk of gallstones

Question 25

Two fibric acid derivative

Answer 25

Gemfibrozil, Fenofibrate

Question 26

Mecahnism of action for fibric acid derivatives

Answer 26

PPAR ligands

Question 27

Lipoprotein effects of fibrates

Answer 27

reduce VLDL, inc HDL, tri reduced by 50%, HDL increased up to 15%

Question 28

Adverse effects of Fibric acid derivatives

Answer 28

GE reflux, diarrhea, increased liver enzymes

Question 29

Fenofibrate can do what to creatinine levels

Answer 29

increase them

Question 30

PPAR alpha does what

Answer 30

Suppresses transcription of APOCIII which inhibits LPL. This leads to increased LPL activity which clears triglycerides from VLDL

Increased APO AI synthesis leads to more HDL

Increases phospholipid transfer protein leads to the transfer of PL from VLDL to HDL

Increased fatty acid oxidation leads to less triglyceride synthesis

Increaed biliary cholesterol excretion

Question 31

Nicotinic acid mechanism

Answer 31

Niacin inhibits mobilization of FFA from adipocytes, reduces hepatic triglyceride synthesis, Reduces ApoB synthesis and secretion (VLDL), promotes VLDL to LDL

Question 32

Nicotinic acid effects

Answer 32

Increases HDL-C
Reduces LDL

Question 33

Nicotinic acid side effects

Answer 33

cutaneous flushing, hepatic failure, GI irritation

Question 34

N-3 fatty acids

Answer 34

omega 3, fish oil, Lower Triglycerides,