Pharmacology - Dyslipidemia Part 1

Question 1

true or false

diabetes can contribute to the development of atherosclerosis

Answer 1

true

Question 2

true or false

there is usually not 1 single cause of atherosclerosis

Answer 2

true

Question 3

atherosclerosis leads to _____, which leads to _____, and then _____

Answer 3

CAD (coronary artery disease), angina (can be due to thrombosis), heart attack

Question 4

what is angina

what is the usual cause?

Answer 4

reduced blood flow to the heart muscle

usually caused by CAD, or thrombosis can cause

Question 5

name 5 things that can prevent CV diseases such as atherosclerosis, CAD, angina, and ultimately heart attack

Answer 5

diet
exercise
destress
medicines
surgery (only a temporary fix – unless you change other factors as well)

Question 6

LDL cholesterol is high in ____

Answer 6

high in fat

Question 7

true or false

we WANT HDL cholesterol to be high

Answer 7

true

Question 8

how is fat (insoluble in water) transported through the blood?

Answer 8

by lipoproteins

Question 9

what does lipoprotein lipase do?

Answer 9

breaks fat to give free fatty acids

breaks down VLDL to IDL, and then LDL

also, breaks chylomicrons into remnants

Question 10

in times of fasting, what happens to fat?

Answer 10

it is converted to sugar - to maintain blood sugar

Question 11

IDL undergoes apoprotein ___ mediated binding to LDL receptors and ultimate elimination

Answer 11

Apoprotein E

Question 12

LDL undergoes apoprotein ____ mediated binding to LDL receptors and ultimate fecal elimination

Answer 12

apoprotein B

Question 13

which type of lipoprotein undergoes binding to remnant receptors? through which apoprotein?

Answer 13

chylomicron remnants

apoprotein e

Question 14

around ___% of cholesterol in the body is synthesized (we dont have to eat)

Answer 14

70%

Question 15

**WHERE in the body does the cholesterol biosynthetic pathway occur?

Answer 15

the liver

Question 16

when cholesterol is synthesized in the liver, where does it go next?

Answer 16

into the blood

Question 17

name 2 fibrates

Answer 17

gemfibrozil
fenofibrate

Question 18

name 3 bile acid resins

Answer 18

cholestyramine
colesevelam
colestipol

Question 19

name 2 PCSK9 inhibitors

Answer 19

evolucumab (repatha)
alirocumab (praluent)

Question 20

name 4 misc pharmacotherapy options for lowering cholesterol that are not part of a specific class

Answer 20

niacin
fish oil
ezetimibe
bempedoic acid

Question 21

true or false

lipid lowering agents are taken with diet, exercise, and lifestyle modifications, or else not much change will be observed

Answer 21

true

Question 22

which class of individuals DO NOT GET LIPID LOWERING AGENTS - CONTRAINDICATED

Answer 22

pregnancy and breastfeeding

Question 23

name 2 high risk individuals who should def get lipid lowering agents

Answer 23

atherosclerosis and pancreatitis

Question 24

when administering lipid-lowering agents, doses of _____ may need to be adjusted

Answer 24

anticoagulants - like warfarin

Question 25

what is the "widely used, standard therapy for acute coronary syndromes"

Answer 25

statins

Question 26

statins are structural analogs of...

Answer 26

HMG-CoA intermediate

Question 27

explain how statins work in relation to the body (not just the enzyme they inhibit)

Answer 27

they decrease oxidative stress and vascular inflammation they stabilize the lesions of atherosclerosis --- preventing pieces from breaking off and moving to other places

Question 28

___ and ___ are inactive lactone prodrugs where are they hydrolyzed? to what?

Answer 28

simvastatin and lovastatin hydrolyzed in the GI tract to the active beta hydroxy derivtatives

Question 29

name 3 Fluorine-containing statins. are they prodrugs?

Answer 29

NO atorvastatin, fluvastatin, rosuvastatin

Question 30

true or false simvastatin is a prodrug

Answer 30

true

Question 31

true or false atorvastatin is a prodrug

Answer 31

false

Question 32

true or false lovastatin is a prodrug

Answer 32

true

Question 33

in order for some statins to be active, their _____ has to be hydrolyzed to ____

Answer 33

lactone ring needs to be hydrolyzed to beta hydroxy acid (active form)

Question 34

*******explain the inhibition of statins

Answer 34

COMPETITIVE and REVERSIBLE

Question 35

*true or false statins are competitive and irreversible inhibitors of HMG-CoA reductase

Answer 35

FALSE competitive and reversible

Question 36

name 4 important functions of cholesterol in the body

Answer 36

membrane component steroid synthesis vitamin D bile acids

Question 37

how do statins affect the liver and how does this affect cholesterol?

Answer 37

increase high affinity LDL receptors on the liver increases the amount of LDL cholesterol excreted through the feces -- good!

Question 38

aside from lowering LDL cholesterol, how do statins affect HDL? do they affect triglycerides?

Answer 38

small increases in HDL (good) decrease blood triglyceride levels

Question 39

true or false statins decrease the risk of new coronary events and stroke due to atherosclerosis

Answer 39

true

Question 40

true or false all statins are given orally

Answer 40

true

Question 41

****explain the first pass effects of statins

Answer 41

EXTENSIVE 1ST PASS into liver through OATP1B1 (organic anion transporting polypeptide 1b1)

Question 42

**true or false since statins are neutral, they are able to get into the liver for metabolism without the help of a transporter

Answer 42

FALSE they are acidic and need a transporter - OATP1B1

Question 43

true or false all statins should be taken in the evening

Answer 43

false all of them with a short half life should, but atorvastatin and rosuvastatin have a long half life and can be taken at any time

Question 44

WHY should statins that have less than a 4 hour half life be taken in the evening?

Answer 44

bc cholesterol biosynthesis peaks after dinner. so it will have the most effect

Question 45

true or false the metabolites of all statins have some active action in inhibiting HMG-CoA reductase

Answer 45

FALSE all do except fluvastatin and pravastatin

Question 46

true or false statins are not highly protein bound is this important for DDI concern

Answer 46

false - they are not really that important for DDI - but can be concerning for AE

Question 47

MAJOR route of elimination of statins minor?

Answer 47

major - by the liver -> bile -> feces minor - through the urine

Question 48

name the statins metabolized by CYP3A4

Answer 48

SAL simvastatin atorvastatin lovastatin

Question 49

name the statin(s) metabolized by CYP2C9

Answer 49

fluvastatin

Question 50

name the statin that is excreted largely unchanged bc it is water soluble

Answer 50

pravastatin

Question 51

the name statin that only goes through phase 2 metabolism (glucuronidation)

Answer 51

pitavastatin

Question 52

2 CYPS that metabolize rosuvastatin which is the main?

Answer 52

CYP2C9 and CYP2C19 CYP2C19 is the main one

Question 53

true or false while pregnant women cannot be given lipid-lowering agents, breastfeeding women can

Answer 53

FALSE - neither can

Question 54

statins can be used alone OR with what other options

Answer 54

resins niacin ezetimibe

Question 55

concern when a patient is on a statin and a resin

Answer 55

cannot take at the same time!! but can take same day give statin AT LEAST 1 hour before resin if resin already taken, wait 4 hours before taking statin

Question 56

are children normally given statins?

Answer 56

no - only in some patients who have familial hypercholesterolemia

Question 57

for all statins: the dose-effect relationship shows that the efficacy of LDL lowering is______ ________

Answer 57

log linear

Question 58

differentiate between what effect high/moderate/low intensity statins have on LDL cholesterol

Answer 58

high intensity - LDL lowering by 50% or more moderate - 30% - less than 50% lowering low - less than 30% lowering

Question 59

what are the only 2 high intensity statins and what are the doses

Answer 59

atorvastatin 40-80mg rosuvastatin 20-40mg

Question 60

major AE of statins what can it progress to?

Answer 60

MYOPATHY - mild muscle soreness or weakness can progress to life-threatening rhabdomyolysis (muscle breakdown)

Question 61

another AE of statins aside from myopathy

Answer 61

hepatotoxicity (rare)

Question 62

true or false statins are CI in pregnancy

Answer 62

true

Question 63

if a patient is trying to get pregnant, should they continue taking the statin until they are confirmed pregnant?

Answer 63

NO should stop prior to conception

Question 64

2 AE of statins aside from myopathy/rhabdo and hepatotoxicity

Answer 64

cognitive SE (nerologic - rare) hyperglycemia - can cause diabetes!

Question 65

what test can be done to monitor a patient's liver function while they are on a statin

Answer 65

transaminase testing (AST/ALT)

Question 66

true or false statins commonly interact with fibrates

Answer 66

true - esp gemfibrozil

Question 67

name 3 drugs that may increase the risk of statin-induced myopathy

Answer 67

niacin protease inhibitors (HIV) amiodarone

Question 68

what was the first statin

Answer 68

lovastatin

Question 69

true or false lovastatin does not contain a lactone ring

Answer 69

FALSE - it does. it is a prodrug and hydrolyzed in vivo

Question 70

true or false CYP3A4 inhibitors taken with lovastatin increases the risk of myopathy

Answer 70

true

Question 71

interaction between cyclosporine + lovastatin

Answer 71

cyclosporine inhibits the OATP1 transporter therefore, lovastatin levels will increase in the blood

Question 72

true or false atorvastatin is not a prodrug

Answer 72

true

Question 73

when should atorvastatin be discontinued

Answer 73

if symptoms of renal failure or myopathy due to rhabdomyolysis develop

Question 74

2 monitoring parameters for atorvastatin (and really all statins)

Answer 74

liver function test (hepatotoxicity) creatine kinase (elevated levels indicate muscle damage!)