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Flashcards in hypolipidemic drugs Deck (40):
1

LDL

low density lipoproteins
- transports cholesterol from liver to the blood stream
- aka "bad cholesterol"
- high levels in the blood are associated with an increased risk of atherosclerosis and coronary artery disease
- normal 100 start treatment

2

HDL

High density lipoprotein
- "good cholesterol"
- HDLs acquire cholesterol from peripheral tissue i.e. arterial walls
- low HDL levels = risk factor for cardiovascular disease
-

3

LP(a) Lipoprotein

formed from a LDL-like moiety and LP(a) protein
- highly homologous to plasminogen but lacks the ability to be activated by tPA
- repair of vessels

4

competitive inhibition

has same Vmax different Km

5

noncompetitive inhibition

has same Km different Vmax (squashed graph)

6

Cholesterol metabolism

?

7

statins

simvastatin
fluvastatin
atorvastatin
pravastatin
lovastatin

8

statins use and MOA

* lower LDL levels (by almost 60% ; TG down 40%)
MOA: competitive inhibitors of HMC-CoA reductase
- leads to an induction of high affinity LDL receptors--> thus lowering serum LDL levels
- increasing LDL receptors is the important part of the mechanism!!

clinically all statins have the same efficacy

9

statin side effects

1. elevations of serum aminotransferase and hepatotoxicity (increase in liver enzymes ALT/AST)
2. myositis (muscle pain), marked by elevated creatine kinase activity
- if drug is not discontinued, rhabdomyolysis may occur--> producing myoglobinemia --> may lead to acute renal failure

*always monitor liver enzymes and creatine kinase when giving statins!

10

statin drug interactions

- drugs that may inhibit CYP enzymes (erythromycin, ketoconazole) will increase the plasma concentrations of statins
- concomitant use of amiodarone (class 3) or verapamil (class 4) or fibrates causes an increased risk of myopathy

*statin + BABR/ezetimibe (which works better in conjunction with statins)

*never use statins + fibrate bc toxicity! (myositis)

* never combine statins + niacin bc toxicity! (myositis)

11

niacin

aka nicotinic acid
**when used in high doses**

12

Niacin MOA and use

- water soluble VB3 which is converted in the body into nicotinamide adenine dinucleotide (NAD) but in high [ ]
- decreases plasma LDL levels and VLDL **
- markledly decreases plasma TG levels
mechanism primarily involves the inhibition of VLDL synthesis and esterification of Fatty Acids in the liver

13

Niacin Side Effects

- flushing (PGE2--> vasodilation--> flushing.....treated by aspirin or other NSAIDS)
- diarrhea
- hyperuricemia (can precipitate gout)
- hyperglycemia (so statins are preferred in diabetics)

14

Fabric Acid Derivatives and use

Gemfibrozil
Fenofibrate

Use: Increases the activity of LPL and Reduces VLDL levels, especially TG!!!

15

Fenofibrate MOA and use and A/E and drug interactions

MOA: agonist at peroxisome proliferator-activated receptor alpha (PPARalpha) which is a nuclear receptor

* PPARalpha affects genes necessary for carb and fat metabolism --> activation --> increase plasma HDL and decrease plasma TG

- increases the activity of lipoprotein lipase!!
- reduces VLDL levels esp lowers triglycerides

Use: typically used to treat hypertriglyceridemias
(preferred over statins)

A/E:
- GI symptoms
- myopathy (increased with given with statins)
- risk of cholesterol gallstones

Major Drug Interactions:
- fabric acid derivatives can displace other albumin bound drugs like warfarin--> thereby increase the anticoagulant effect of warfarin and sulfonyl ureas

16

Bile Acid Binding Resins and use

Colestipol
Cholestyramine
Colesevelam

Use: DECREASE LDL levels and INCREASE HDL

17

drugs that may inhibit CYP enzymes

erythromycin (macrolide antibiotics)
ketoconazole
cimetidine
SSRIs
fluoroquinolones
HIV protease inhibitors
grapefruit juice

18

CYP450 enzyme INDUCERS

rifampicin
barbiturates
phenytoin
carbamazepine
glucocorticoids
chronic alcohol administration

19

Gemfibrozil MOA and use and A/E and drug interactions

MOA: agonist at peroxisome proliferator-activated receptor alpha (PPARalpha) which is a nuclear receptor

* PPARalpha affects genes necessary for carb and fat metabolism --> activation --> increase plasma HDL and decrease plasma TG

- increases the activity of lipoprotein lipase!!
- reduces VLDL levels esp lowers triglycerides

Use: typically used to treat hypertriglyceridemias
(preferred over statins)

A/E:
- GI symptoms
- myopathy (increased with given with statins)
- risk of cholesterol gallstones

Major Drug Interactions:
- fabric acid derivatives can displace other albumin bound drugs like warfarin--> thereby increase the anticoagulant effect of warfarin and sulfonyl ureas

20

Colestipol: use, MOA, A/E and drug interactions

**Decreases LDL levels and increases HDL

MOA:
- bind bile acids in the intestine forming a complex that is excreted in the feces
- this leads to an increased oxidation of cholesterol to bile acids in the liver
- this results in an increase in the number of low-density lipoprotein receptors --> thereby decreasing serum LDL levels

Side Effects:
- constipation
- bad taste (may lead to compliance issues)
- deficiency of fat-soluble vitamins (as these resins bind bile acids they may interfere with normal fit digestion and absorption and thus may prevent absorption of fat soluble vitamin such as A, D, E and K)

* side effects can even be seen at therapeutic doses compared to toxicities which are seen at higher than therapeutic doses*

Drug Interactions:
- may delay or reduce the absorption of other concomitant oral medications i.e. digitalis, warfarin

21

Side Effects vs Toxicities

* side effects can even be seen at therapeutic doses compared to toxicities which are seen at higher than therapeutic doses*

22

patient has flushing. what drug did you give the patient and how do you treat it

the patient was given Niacin to lower LDL and VLDL

you treat this with aspirin or other NSAIDs

23

cholestyramine: use, MOA, A/E and drug interactions

**Decreases LDL levels and increases HDL

MOA:
- bind bile acids in the intestine forming a complex that is excreted in the feces
- this leads to an increased oxidation of cholesterol to bile acids in the liver
- this results in an increase in the number of low-density lipoprotein receptors --> thereby decreasing serum LDL levels

Side Effects:
- constipation
- bad taste (may lead to compliance issues)
- deficiency of fat-soluble vitamins (as these resins bind bile acids they may interfere with normal fit digestion and absorption and thus may prevent absorption of fat soluble vitamin such as A, D, E and K)

* side effects can even be seen at therapeutic doses compared to toxicities which are seen at higher than therapeutic doses*

Drug Interactions:
- may delay or reduce the absorption of other concomitant oral medications i.e. digitalis, warfarin

24

Ezetimibe: use & toxicity

(zetia*)
- Prodrug
- lowers serum LDL and TG*
- decreases GI absorption of cholesterol
- used alone reduces LDL by 18% but MUCH more effective when given with statins (72%)

Toxicity: well-tolerated, MC side effect = diarrhea, abdominal pain

25

MOA = decrease synthesis of VLDL

name that drug!

Niacin

26

MOA = decrease cholesterol synthesis and increase LDL receptors

name that drug!

statins

27

MOA = interrupts enterohepatic circulation of bile acids and increases synthesis of bile acids and LDL receptors

name that drug!

Bile acid binding resins

Colestipol
Cholestyramine
colesevelam

28

colesevelam: use, MOA, A/E and drug interactions

**Decreases LDL levels and increases HDL

MOA:
- bind bile acids in the intestine forming a complex that is excreted in the feces
- this leads to an increased oxidation of cholesterol to bile acids in the liver
- this results in an increase in the number of low-density lipoprotein receptors --> thereby decreasing serum LDL levels

Side Effects:
- constipation
- bad taste (may lead to compliance issues)
- deficiency of fat-soluble vitamins (as these resins bind bile acids they may interfere with normal fit digestion and absorption and thus may prevent absorption of fat soluble vitamin such as A, D, E and K)

* side effects can even be seen at therapeutic doses compared to toxicities which are seen at higher than therapeutic doses*

Drug Interactions:
- may delay or reduce the absorption of other concomitant oral medications i.e. digitalis, warfarin

29

MOA = increase LPL and TG hydrolysis

name that drug!

Fibrates

gemfibrozil
fenofibrate

30

MOA = decrease intestinal absorption of cholesterol

name that drug!

Ezetimibe

31

drug causes flushing, diarrhea, hepatic dysfunction, nausea, pruritus and gout

name that drug!

niacin

32

drug causes hepatotoxicity and myopathy

name that drug!

statins

33

drug causes hepatotoxicity, nausea and myositis

name that drug!

Fibrates

gemfibrozil
fenofibrate

34

drug causes GI disturbances

name that drug!

exetimibe

35

drug causes constipation, bloating, nausea and fat soluble vitamin deficiency

name that drug!

Bile acid binding resins

Colestipol
Cholestyramine
colesevelam

36

during drug treatment with atorvastatin it is important to routinely monitor serum concentrations of

alanine and aspartate transaminases and creatine kinase

37

two primary adverse effects HMG CoA inhibitors

hepatotoxicity and myopathy

38

dyslipidemia

general term associated with high cholesterol and/or high triglyceride (TG) levels in plasma.

39

CYP450 enzyme inducers

- rifampicin
- barbiturates
- phenytoin
- carbamazepine
- glucocorticoids
- chronic alcohol use

40

CYP450 enzyme inhibitors

- cimetidine
- SSRIs
- ketoconazole
- macrolide antibiotics
- fluoroquinolones
- HIV protease inhibitors
- grapefruitjuice