Dislipidemia Drugs- Melissa (3)* Flashcards Preview

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Flashcards in Dislipidemia Drugs- Melissa (3)* Deck (59):
1

4 disease states that raise cholesterol levels:

1. Biliary Disease
2. Renal Disease
3. Hypothyroidism
4. Diabetes Mellitus *respond well to STATINS*

2

Three disease states that raise TG levels:

1. Alcoholism
2. Renal Disaese
3. Diabetes Mellitus

3

Ideal levels:
1. cholesterol
2. LDL-C
3. TG

Cholesterol: UNDER 200
LDL-C: UNDER 100 (acceptable = 100-129)
TG: UNDER 150

4

Primary causes of hyperlipidemia (2)

diet
genetics

5

3 secondary causes of hyperlipidemia:

Drugs (Propranolol, HTZ), Disease (DM), ETOH abuse

6

What is the first line therapy in hyperlipidemia?

DIET MODIFICAITON:
- Decrease fat (TGs, etc.), carbs, ETOH
- Increase exercise--> ^HDL prodxn

7

Cholestyramine, Colesnvelam, Colestipol
Drug Class, ROA, MOA?

Resins: Aways start with chol/col

ROA:
PO w/ lots of fluid; NOT ABSORBED GI--> NO bioavailability!

MOA:
Bind bile acids in sm. intestine-->
^ Fecal bile acid excretion-->
DECREASE neg. feedback on *7a-HYDROXYLASE*-->
^ Liver conversion cholesterol--> bile acid -->
DECREASE circulating cholesterol

8

How is Colesevelam administered? Why is this important?

Administered as a capsule w/ liquid; becomes gel in GI tract
*Less GI sx*; better patient compliance

9

Therapeutic use for Resin drugs?
How long do they take for max effect?
What is max effect?

- Tx ^ cholesterol (~combo treatment for ^ TG/^C pts)
- 4 weeks to max effect= 20% reduction plasma LDL-C

10

Which patient populations can take resins safely (2)?
Why is this relevant?

preggos/ nursing; kiddos +6yrs

*Good alternative to statins which cannot be used in pregnancy or in children under 8yoa

11

Resins ADRs; when are they worse?

GI sx: bloating, constipation, abdominal pain
*Worse if patients don't take enough fluid!

12

DD interactions with resins--what is the cause?
How do we avoid this?

Resins compromise absorption of fat sol vitamins and drugs
*Take drug 1 hr before or 4 hrs after resin

13

MOA for all statin drugs?
Recall the two ultimate effects:

Competitive inhib. HMG-CoA Reductase (RLS cholesterol synth.)--> DECREASE *INDOGENOUS* CHOLESTEROL SYNTH. --> **^ LDL-Rs in LIVER** + **^ HDL levels**

14

Therapeutic use for ALL statin drugs (2)?
Time to max effect?

Hypercholesterolemia; combo tx. in patients with ^ TGs
**2 weeks to max effect

15

Which two drugs are the most effective statins and can be used to treat ^ TGs?
Why are they so effective (2)?

Atorvastatin, Rosuvastatin
- Longer t 1/2
- ^ LDR # the most--> LDLR binds APOE--> ^ IDL clearance (w/TGs)

16

Which statin drug can treat kids 8+ yoa?
Why?
What is the age cut off for all other statin drugs?

Pravastatin 8+ yoa (less side effects)
Other Statins 10+ yoa

Pr= Prim, little sister (maybe 8 years old in the first hunger games movie?)

17

At what time of day does cholesterol synth. peak?
Which statin drugs are taken at night (3)?

Cholesterol synth. peaks b/w 12-2AM
Lova-, Fluva-, Simvastatin

Leah is Fast aSLeep at night. (LFS = night time drugs)
**This was a good one, thank you! :)**

18

Which statin drug should be taken at dinner (w. food)?

Lovastatin

Leah Loves Food!
Take the "L" drug with food!
**Also excellent, thank you!!**

19

Which two statin drugs can not be taken with food (dec. absorption)?

Prava-, Pitavastatin

Both start with "P". Don't take the "p" drugs when you eat your "peas".
**PRAy for PITA but don't eat it!**

20

Two prominent ADRs of statin drugs:

-Hepatic dysfunciton (^ALT, AST)
-Myalgia (^CPK) ***STOP DRUG***

21

Factors that increase hepatic ADRs of statin drugs (3)

-^dose statin
-gemfibrosil or nicotinic acid
-CYP3A4 inhibitors (ketoconazole, erythromycin)

22

Which two statins cause the LEAST ADRs?

Fluvastatin, Pravastain (KIDDOS 8+ yoa!)
--> Consequently, these are also the least potent/ cause the smallest cholesterol reduction.

23

3 contraindications for statins:

-PREGGOS X!!!/ nursing
-Liver disease
-Kiddos under 8/10

24

Which two statins are prodrugs?
Two potential factors compromising their safety of use?

Lova-, Simvastatin
CYP3A4 inhibitors, Grapefruit juice
*Atorvastatin not prodrug, but met. by CYP3A4

"LOve SIMone; she's a pro."
or "Leah's SIMply a PRO at school :)"

25

Which 2 statins are metabolized by CYP2C9?

Rosuva-, Fluvastatin

It would be *Freaking *Ridiculous 2 C 9 monkeys at the BCC!

26

Which statin is metabolized by CYP2D6?
2 clinical implications?

Simvastatin
1. CYP2D6*4 allele--> slow metabolizers--> longer t 1/2
2. SCLO1B1 SNP--> poor hepatic uptake--> ^ plasma levels
--> more ADRs (MSK pain!)

27

SCLO1B1 SNP: clinical significance?

Simvistatin; low hepatic absorption and more MSK pain!
Give these patients lower Simvastatin doses.

28

Ezetimibe:
MOA?
Describe administration regimen?

Targets *DIETARY cholesterol*
Once daily dosing

MOA:
INHIBIT NPC1L1 transporter--> DECREASE cholesterol absorption at brush boarder enterocytes (sm. intestine)

29

Therapeutic uses for Ezetimibe (2) :

Hypercholesterolemia (decrease LDL-C 20%) independently or combo tx

*DOUBLE Statin effectiveness*

30

2 ADRs of Ezetimibe:

Diarrhea with fatty meals; Hepatic dysfxn.

*Your poops come out too EZ :)*💩

31

Contraindications to Ezetimibe use (2):

-Hepatic disease (enterohepatic recirculation)
-Resins decrease absorption

32

Alirocumab, Evolocumab:
Drug class + MOA?
ROA + Dosing regimine?

Remember. --mab = monoclonal antibody

PCSK9 Inhibitors
Inhibit PCSK9 binding LDL-Rs-->
STOP targeting endocytosed receptors for destruction-->
^ LDL-R recycling--> ^ # LDL-Rs

*IV infusion every 2-4 weeks

33

ADRs of PCSK9 Inhibitors:

Hypersensitivity
-others really unknown because these are so new

34

Gemfibrozil, Clofibrate, Fenofibrate, Benzafibrate

Drug Class?
MOA ( + 3 effects)?

Fibrates (have fibr in name)

MOA:
Bind + stimulate PPAR-a -->
1. ^ FA oxidation/LPL--> DECREASE FFA
2. ^ APO AI/AII--> ^ HDL (15%)
3. DECREASE APO CIII--> ^LPL--> DECREASE VLDL

35

2 ADRs of Fibrate drugs--which drugs/ circumstances are worst?

-Gallstones (worst = Clofibrate)
-Myopathy (statin combo>>>)
(worst = Gemfibrosil, Clofibrate)

36

Which fibrate drug causes the LEAST myopathy?

Fenofibrate

*FEeel NO pain with FENOfibrate*

37

Describe why fibrate drugs cause worsened myopathy when combined with statins:

Which statins are affected the worst (3)?

Block OATP2 transporter--> can't clear statins from liver--> ^ conc. in circ--> ^ MSK sx.

*statins affected = prava-, atorva-, rosuvastatin

When the fibrates ruin the OATs, the PARty is ruined! We can't have no bake cookies without OATmeal. No cookies = sucky PARty.
PAR = prava, atorva, rosuvastatin

38

3 contraindications for fibrate drugs

gallbladder/ liver/ renal disease

39

Nicotinic Acid:
MOA (2)

1. INHIBIT hormone sensitive lipase (adipose cells) --> Decrease lipolysis of fats --> DECREASE FFA return to liver

2. ^LPL --> ^ VLDL clearance

(Thank you! :) )

40

Which two classes of drugs are used to treat elevated blood triglycerides?
How do they work?

Fibrates and Nicotinic Acid
1. Fibrates: through PPARa
2. Nicotinic acid through hormone sensitive lipase

41

Two caveats to administration of nicotinic acid:

1. CAN'T INTERCHANGE immediate and XR versions
(will ^ ADRs)

2. MUST TITRATE DOSE over 4 weeks to the therapeutic dose of 2-6 g/d (will ^ ADRs otherwise.... Like flushing and itching)

42

6 Most common ADRs asstd. with nicotinic acid:

-Itching/ Flushing*** (admin ASA ***to prevent flushing)
-PEPTIC ULCERS***
-HYPERURICEMIA (Gout)***
-GLUCOSE INTOLERANCE (DM)***
-Liver disease
-Myopathy w/ Statins

43

3 Contraindications for nicotinic acid use:

Bleeding disorders, peptic ulcers, Liver disease

(probably gout and DM too if conditions are severe...)

44

Familial Hyperchylomicronemia (type 1):
Describe disease + Treatment

Defective LPL or APOCII--> ^ TG/chylomicrons w. 12 hr fast

TX:
-Diet (limit carbs + fats)
-Fibrates + Nicotinic acid- because this is a TG problem! Not cholesterol.

45

Familial Hypercholesterolemia (IIa):
Describe disease + Drug Treatment

Impaired LDL-C clearance *HIGHEST RISK CVD*

TX:
#1 Statins
-possible combo w/ Ezetimibe or Resin
(B/c this is a CHOLESTEROL problem!)

46

Familial Combined Hyperlipoproteinemia (IIb):
Describe disease + Drug Treatment

^ TG, ^ Cholesterol

TX:
#1 Statins (Atorvastatin or Rosuvastatin are best- because this is a TG AND CHOLESTEROL problem)
Possible combo w/ nicotinic acid

47

Familial Dysbetalipoproteinemia (III):
Describe disease + Drug Treatment

*Abnormal APOE2*--> Can't clear VLDL properly-->
^ TG/cholest., ^IDL + chylomicrons
...Basically, all of the levels are messed up.

TX: #1 Fibrates (DECREASE TG 50%)
*I don't know a logical reason for not treating the cholesterol issue. *Me either, this perplexed me.

48

Familial hypertriglyceridemia (IV)
Describe disease + Drug Treatment

Which drug makes it worse?

^ TG/ VLDL w/ asstd. hyperuricemia + glucose intolerance

TX: #1 Fibrates

*NICOTINIC ACID will WORSEN uricemia/ glucose intol.!*

49

Thiazide diuretics effect on lipid profile:

^ cholesterol + ^ TG 10-15%

50

Non-specific B-Blockers (propranolol) effect on lipid profile:

^ TG
DECREASE HDL

51

OCPs effect on lipid profile:

^TG

52

Of all drugs to treat Dislipidemia, which are not labeled to cause hepatic dysfunction/ aren't specifically contraindicated in hepatic failure?

Resins (Because they have no bioavailability)
PCSK9i's (maybe because not enough research yet)

53

NPC1L1 transporter is inhibited by which drug?

Ezetimibe

54

Worst three statins to combine with fibrate drugs:

prava-, atorva-, rosuvastatin

55

What do you give patients to prevent itching/ flushing induced by nicotinic acid?

ASA prophylaxis

56

Which familial lipid disorder has the highest associated risk for CVD?

Familial Hypercholesterolemia (IIa)

57

Three well known CYP3A4 inhibitors

--Azoles (antifungals)
--grapefruit juice
--erythromycin

58

What are types:
I, IIA, IIB, III, and IV dislipidemia?

I. Hyperchylomicronemia
IIA. Hypercholesterolemia
IIB. Combined Hyperlipidemia
III. Dysbetalipoproteinemia
IV. Hypertriglyceridemia (the one with glucose/utricle acid issues)

59

Which drugs have the following effects?
^TG/cholesterol
^ TG
^TG/ decreased HDL

^TG/cholesterol- Thiazides
^ TG- OCPs
^TG/ decreased HDL- BBers