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Flashcards in Hyperlipidemia Treatment Deck (34):
1

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

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.

2

What is the effect of statins?

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

3

What are the major drug interactions for statins

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.

4

Why do statins have such a low bioawvailabilty?

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

5

Adverse Effects of Statins

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

6

WHat do Bile Acids do?

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

7

What are the advantages of Bile Acid sequestrants?

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

8

What effect do bile acid sequestrants have on cholesterol levels

Lowers LDL by 25%...not as effective as Statins

9

Bile Acid Sequestrants adverse effects

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

10

Cholesterol Absorption Inhibitors prototype drug

Ezetimibe

11

How does Ezetimibe work>

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

12

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

no

13

Ezetimibe drug interactions

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

Cyclosporine increases ezetimible levels

14

Fibric Acid Derivatives do what?

Reduce VLDL and triglycerides and raise HDL

15

Lipoproteins

Macromolecular complexes in the blood that transport lipids

16

Atorvastatin Metabolized how and where?

CYP3A4, beta oxidation, hydroxylation. 
Fecal excretion

17

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

Because some statins, like provaststin are excreted renally

18

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

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

 

19

Gemfibrozil given with a statin 

equals rhabdomyolysis

20

Bile Acid Sequestrants prevent absorption of what other drugs

Beta Blockers, Digoxin, Thyroxine, Coumadin

21

Bile acid sequestrants side effects

Constipations, farting, fecal impaction

22

Bile Acid sequestrants contraindicated in who?

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

23

Ezetimibe

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

24

What should you not give Ezetimibe with

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

25

Two fibric acid derivative

Gemfibrozil, Fenofibrate

26

Mecahnism of action for fibric acid derivatives

PPAR ligands

27

Lipoprotein effects of fibrates

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

28

Adverse effects of Fibric acid derivatives

GE reflux, diarrhea, increased liver enzymes

29

Fenofibrate can do what to creatinine levels

increase them

30

PPAR alpha does what

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

 

31

Nicotinic acid mechanism

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

32

Nicotinic acid effects

Increases HDL-C
Reduces LDL

33

Nicotinic acid side effects

cutaneous flushing, hepatic failure, GI irritation

34

N-3 fatty acids

omega 3, fish oil, Lower Triglycerides,