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Flashcards in Antihyperlipidemic Drugs Deck (35):
1

increased risk of cardiovascular mortality is closely linked to what

elevated level of LDL cholesterol
decreased level of HDL cholesterol
hypertriglyceridemia (esp with low HDLs)

2

other risk factors of cardiovascular diseases

smoking
obesity
diabetes
hypertension

3

primary causes of hyperlipidemia

monogenic diseases
genetic polymorphisms
gene environment interactions

4

how does excessive alcohol intake cause VLDL production

alcohol increases the synthesis of FA which are esterified to form triglycerides

5

how does type II DM cause hyperlipidemia

- insulin suppresses VLDL production by the liver but with insulin resistance in type II DM, there is lack of suppression and increased VLDL production

- also apoCIII levels are increased with insulin resistance leading to reduced breakdown of chylomicrons and VLDL

6

common secondary causes of hyperlipidemia

-hypertrigylcerides: DM, renal failure, hypothyroidism, alcohol excess, contraceptives, beta blockers, glucocorticoids

-hypercholesterolemia: hypothyroidism, nephrotic syndrome, obstructive liver disease, glucocorticoids

7

what can dyslipidemia cause

symptomatic vascular disease such as CAD and peripheral artery disease

high TGs can cause acute pancreatitis

8

how to diagnose hyperlipidemia

- measure serum lipids after 10 hour fast: gives you tot cholesterol, TGs, and HDL

-if TGs is less than 400mg/dL and patient has been fasting, LDL = TC - [HDL + (TG/5)]

9

5 main classes of drugs available for the treatment of hyperlipidemia

- HMG-CoA reductase inhibitors
- Niacin
- Bile acid binding resins
- Cholesterol absorption inhibitors
- fibrate derivatives

10

what are the HMG-CoA reductase inhibitors

FiRe SLAP

Fluvastatin
Rosuvastatin
Simvastatin
Lovastatin
Atorvastatin
Pravastatin

11

mechanism of statins

- competitive inhibitor of HMG-CoA reductase the enzyme that catalyzes the first committed step of cholesterol synthesis
- therefore deplete intracellular cholesterol
- upregulation of LDL receptors
- increased clearance of LDL from the blood
- improve endothelial functions
- decrease platelet aggregation
- stabilize atherosclerotic plaque
- reduce inflammation

12

statin in order of decreased potency in lowering TGs and LDL

Rosuvastatin, Atorvastatin, Simvastatin, Lovastatin = Pravastatin, then last is Fluvastatin

RAS LP F

13

which statins are prodrugs and how are they activated

Lovastatin and Simvastatin which are inactive lactones that are hydrolyzed in the GI to yield the active beta hydroxyl derivatives

14

clinical uses of statins

- drug of choice for LDL reduction
- reduce cardiovascular mortality
- useful also when combined with bile acid binding resins, niacins, or ezetimbe

15

who does statins not benefit

those who are homozygous for familial hypercholesterolemia IIA because they have non functional LDL receptors

16

what types of people should not take statins

women who are pregnant, lactating, or likely to become pregnant

17

four major statin benefit groups

- pts with clinical atherosclerotic cardiovascular disease (ASCVD)
- pts with LDL 190mg/dL or higher
- pts 40-75 with diabetes and LDL 70-189mg/dL
- pts without ASCVD or diabetes with LDL 70-189mg/dL and an estimated 10 year risk of ASCVD or higher

18

adverse effects of statins

- elevation of aminotransferases
- myopathy and rhabdomyolysis

19

most effective drug for increasing HDL and most may reduce lipoprotein a

niacin

20

mechanism of niacin

- inhibits adenylyl cyclase in adipocytes (via Gi) --> inhibition of hormone sensitive lipase --> reduces transport of fatty acids to liver and decreases hepatic TG synthesis
- decreased TG --> decreased VLDL production --> reduced LDL levels
- increases LPL --> increases clearance of chylomicrons and VLDL TGs
- catabolic rate of HDL decreased --> increased HDL

21

uses of niacin

- raise HDL levels
- pts with combined hyperlipidemia with low HDL
- effective with statins

22

adverse effects of niacin

- red flushed face with first dose or increased dose but can be decreased with NSAIDs prior to intake of drug
- Hyperglycemia and Hyperuricemia
- Hepatotoxicity (increased serum transaminases)

4Hs

23

what are the fibrate derivatives

Fenofibrate
Gemfibrozil

24

mechanism of fibrates (name them again)

fenofibrate and gemfibrozil

- activate the nuclear receptor PPAR-α (peroxisome proliferator activated receptor)
- decreased in TGs due to increased expression of lipoprotein lipase, decreased apoCIII (liver), and increased hepatic oxidation of FA

25

uses of fibrates

severe hypertrigylceridemia

26

adverse effects of fibrates

- myositis (inflammation and degeneration of muscle tissues)
- rhabdomyolysis (destruction of striated muscle cell
- lithiasis (gallstones)
- mild GI disturbances

27

types of pts that should avoid fibrates

those with hepatic or renal dysfuncton

28

drug interaction with gemfibrozil

- inhibits hepatic uptake of statins by OATP1B1 hence increasing plasma conc of statins
- also competes for same glucuronosyl transferase that metabolizes most statins hence both drugs will be increased in plasma
- hence higher chance of rhabdomyolysis is more likely

29

what are the bile acid binding resins

cholestyramine
colestipol
colesevelam

30

mechanism of action for bile acid binding resins (name them again)

cholestyramine, colestipol, colesevelam

polymeric anionic exchange resins that are insoluble in water that bind to anionic bile acids in intestinal lumen and preventing their absorption and excrete them in feces --> leads to more conversion of cholesterol to bile acids hence depleting amount of intracellular cholesterol --> upregulation of LDL receptors --> decreased LDL in plasma

partially offset by increased cholesterol synthesis due to upregulation of HMG-CoA reductase

31

uses of bile acid binding resins

- used with statins and niacins to reduce LDL
- drug of choice for children and women planning to become pregnant

32

type of pts that bile acid binding resins are not effective on

those with defective LDL receptors

33

adverse effects of bile acid binding resins (name the drugs again)

cholestyramine, colestipol, colesevelam

GI symptoms: bloating, nausea, cramping, constipation

34

contraindications of bile acid binding resins

those with hypertriglyceridemia because it increase TGs

35

drug interactions of bile acid binding resins

cholestyramine and colestipol impair the absorption of fat soluble vitamins A, D, E, and k

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