drugs to treat hyperlipidemia Flashcards Preview

Pharm block 4 hemostasis and cardiac > drugs to treat hyperlipidemia > Flashcards

Flashcards in drugs to treat hyperlipidemia Deck (83)
Loading flashcards...
1

Protective roles of HDL in the prevention of atherosclerosis

1) HDLs (the “good cholesterol”) inhibit the oxidation of LDLs
- paraoxonase enzyme (PON1) present on HDL surface
- anti-oxidant activity

2) HDLs inhibit the expression of adhesion molecules on the endothelium
-prevents recruitment of monocytes to atherosclerotic plaque

3) HDLs inhibit the formation of FOAM cells

4) HDLs promote REVERSE CHOLESTEROL TRANSPORT
-the transport of cholesterol from the periphery back to the liver where it can be secreted as bile

2

PON1 enzyme

found on HDL's surface and prevents the oxidation of LDL

3

optimal LDL level

4

optimal HDL level

M: >40 mg/dL
W: >50 mg/dL

5

optimal triglyceride level

6

Very high LDL level

>190mg/dL

7

very high triglycerides

>500 mg/dL

8

initial drug of choice for someone with hypercholesterolemia

statin

9

what are the classes of drugs used to treat hyperlipidemia

statins
Bile acid-binding resins
Cholesterol absorption inhibitors
PCSK9 inhibitors

10

what are the bile acid binding resins

Cholestryamine (Questran®)
Colestipol (Colestid®)
Colesevelam (Welchol®)

11

what is the cholesterol absorption inhibitor

ezetimibe

12

what are the PCSK9 inhitibitors

Evolocumab
Alirocumab

13

how do statins work

STATINS competitively inhibit HMG-CoA reductase
- inhibit endogenous cholesterol synthesis

induces the activation of the SREBP transcription factor

14

what is the primary clinical effect of statins

**Significant reduction in LDL-cholesterol (20-60%- dose/drug specific)
Modest reduction in triglycerides (10-20%)
Modest increase in HDL (5-10%)

15

what does SREBP transcription factor regulate

SREBP regulates expression of the LDL receptor gene
- leading to increased expression of the LDL-R at the PM
- increased LDL-R results in increased clearance of serum LDL

16

pathway by which statins work

1. statins inhibit HMG-CoA reductase leading to decreased production of cellular cholesterol
2. decreased cholesterol levels trigger the activation of SREBP transcription factor
3. SREBP activation increases transcription of the LDL receptor gene
4. increased expression of the LEL receptors increase the clearance of LDLs from the serum
5. LDLs are internalized and their cholesterol can be excreted in the bile

17

what 2 things are statins the drug of choice when treating

patients with increased LDL
primary and secondary prevention of CHD

18

primary prevention of CHD

even in patients with no clinical CHD and normal LDL, statin treatment lowered the number of coronary events, CHD death, stroke and total mortality

therefore statins are effective at lowing CHD risk regardless of initial baseline LDL

19

effects of doubling the dose of a statin

very small further reduction in LDL level (5%)
significant increase in adverse effects

20

what are the adverse effects of Statins

GI disturbances *most common
increased liver enzymes (rare)
type-2 diabetes (benefit outweighs risk)

* effects on muscles (common 5-10%)
- myalgia (pain)
-myopathy (weakness)
-dose dependent
- Rhabdomyolysis (rare but serious)

21

what is rhabdomyolysis

muscle inflammation & disintergration (very rare, but v. serious)

22

what increases the chances of rhabdomyolysis in a patient taking statins

taking statin + an interacting drug (cyclosporin, macrolide, ketaconazole)
high doses

associated with a polymorphism in the Statin hepatic anion transporter

23

where are statins absorbed

the intestine 30-85%

Lovastatin, Simvastatin, Atorvastatin undergo metabolism by CYP3A4 in the intestine

24

how does grapefruit juice affect statins

grapefruit juice inhibits CYP3A4 in the intestine therefore preventing metabolism and increasing the bioavailability of the drugs. Could lead to increased risk of adverse effects

25

how are statins taken up by the liver

via the OATP2 transporter

26

where are statins metabolized and excreted

STATINS are metabolized in the liver and excreted in the bile and feces (primarily hepatic excretion)

all STATINS are glucoronidated by glucurornyl transferase enzymes (UGT1A1/1A3)
-facilitates both further metabolism and excretion
- STATINs are variably metabolized by the CYP450 system

27

which statin is not metabolized by CYP450 enzymes

Pravastatin (hepatic and renal excretion)

28

what is responible for low serum concentrations of statins

OATP2 transporter

29

STATINS: Drug interactions

Drugs that inhibit cytochrome P450 enzymes will increase the concentration of specific STATINs leading to increased risk of adverse effects especially myopathy and Rhabdomyolysis

30

which statins are affected by CYP3A4 inhibitors

Lovastatin, Simvastatin & Atorvastatin (LSA) (increases their levels)