Pharmacology - Dyslipidemia Part 1 Flashcards
true or false
diabetes can contribute to the development of atherosclerosis
true
true or false
there is usually not 1 single cause of atherosclerosis
true
atherosclerosis leads to _____, which leads to _____, and then _____
CAD (coronary artery disease), angina (can be due to thrombosis), heart attack
what is angina
what is the usual cause?
reduced blood flow to the heart muscle
usually caused by CAD, or thrombosis can cause
name 5 things that can prevent CV diseases such as atherosclerosis, CAD, angina, and ultimately heart attack
diet
exercise
destress
medicines
surgery (only a temporary fix – unless you change other factors as well)
LDL cholesterol is high in ____
high in fat
true or false
we WANT HDL cholesterol to be high
true
how is fat (insoluble in water) transported through the blood?
by lipoproteins
what does lipoprotein lipase do?
breaks fat to give free fatty acids
breaks down VLDL to IDL, and then LDL
also, breaks chylomicrons into remnants
in times of fasting, what happens to fat?
it is converted to sugar - to maintain blood sugar
IDL undergoes apoprotein ___ mediated binding to LDL receptors and ultimate elimination
Apoprotein E
LDL undergoes apoprotein ____ mediated binding to LDL receptors and ultimate fecal elimination
apoprotein B
which type of lipoprotein undergoes binding to remnant receptors? through which apoprotein?
chylomicron remnants
apoprotein e
around ___% of cholesterol in the body is synthesized (we dont have to eat)
70%
**WHERE in the body does the cholesterol biosynthetic pathway occur?
the liver
when cholesterol is synthesized in the liver, where does it go next?
into the blood
name 2 fibrates
gemfibrozil
fenofibrate
name 3 bile acid resins
cholestyramine
colesevelam
colestipol
name 2 PCSK9 inhibitors
evolucumab (repatha)
alirocumab (praluent)
name 4 misc pharmacotherapy options for lowering cholesterol that are not part of a specific class
niacin
fish oil
ezetimibe
bempedoic acid
true or false
lipid lowering agents are taken with diet, exercise, and lifestyle modifications, or else not much change will be observed
true
which class of individuals DO NOT GET LIPID LOWERING AGENTS - CONTRAINDICATED
pregnancy and breastfeeding
name 2 high risk individuals who should def get lipid lowering agents
atherosclerosis and pancreatitis
when administering lipid-lowering agents, doses of _____ may need to be adjusted
anticoagulants - like warfarin
what is the “widely used, standard therapy for acute coronary syndromes”
statins
statins are structural analogs of…
HMG-CoA intermediate
explain how statins work in relation to the body (not just the enzyme they inhibit)
they decrease oxidative stress and vascular inflammation
they stabilize the lesions of atherosclerosis — preventing pieces from breaking off and moving to other places
___ and ___ are inactive lactone prodrugs
where are they hydrolyzed? to what?
simvastatin and lovastatin
hydrolyzed in the GI tract to the active beta hydroxy derivtatives
name 3 Fluorine-containing statins.
are they prodrugs?
NO
atorvastatin, fluvastatin, rosuvastatin
true or false
simvastatin is a prodrug
true
true or false
atorvastatin is a prodrug
false
true or false
lovastatin is a prodrug
true
in order for some statins to be active, their _____ has to be hydrolyzed to ____
lactone ring needs to be hydrolyzed to beta hydroxy acid (active form)
***explain the inhibition of statins
COMPETITIVE and REVERSIBLE
*true or false
statins are competitive and irreversible inhibitors of HMG-CoA reductase
FALSE
competitive and reversible
name 4 important functions of cholesterol in the body
membrane component
steroid synthesis
vitamin D
bile acids
how do statins affect the liver and how does this affect cholesterol?
increase high affinity LDL receptors on the liver
increases the amount of LDL cholesterol excreted through the feces – good!
aside from lowering LDL cholesterol, how do statins affect HDL? do they affect triglycerides?
small increases in HDL (good)
decrease blood triglyceride levels
true or false
statins decrease the risk of new coronary events and stroke due to atherosclerosis
true
true or false
all statins are given orally
true
**explain the first pass effects of statins
EXTENSIVE 1ST PASS
into liver through OATP1B1 (organic anion transporting polypeptide 1b1)
**true or false
since statins are neutral, they are able to get into the liver for metabolism without the help of a transporter
FALSE
they are acidic and need a transporter - OATP1B1
true or false
all statins should be taken in the evening
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
WHY should statins that have less than a 4 hour half life be taken in the evening?
bc cholesterol biosynthesis peaks after dinner. so it will have the most effect
true or false
the metabolites of all statins have some active action in inhibiting HMG-CoA reductase
FALSE
all do except fluvastatin and pravastatin
true or false
statins are not highly protein bound
is this important for DDI concern
false - they are
not really that important for DDI - but can be concerning for AE
MAJOR route of elimination of statins
minor?
major - by the liver -> bile -> feces
minor - through the urine
name the statins metabolized by CYP3A4
SAL
simvastatin
atorvastatin
lovastatin
name the statin(s) metabolized by CYP2C9
fluvastatin
name the statin that is excreted largely unchanged bc it is water soluble
pravastatin
the name statin that only goes through phase 2 metabolism (glucuronidation)
pitavastatin
2 CYPS that metabolize rosuvastatin
which is the main?
CYP2C9 and CYP2C19
CYP2C19 is the main one
true or false
while pregnant women cannot be given lipid-lowering agents, breastfeeding women can
FALSE - neither can
statins can be used alone OR with what other options
resins
niacin
ezetimibe
concern when a patient is on a statin and a resin
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
are children normally given statins?
no - only in some patients who have familial hypercholesterolemia
for all statins: the dose-effect relationship shows that the efficacy of LDL lowering is______ ________
log linear
differentiate between what effect high/moderate/low intensity statins have on LDL cholesterol
high intensity - LDL lowering by 50% or more
moderate - 30% - less than 50% lowering
low - less than 30% lowering
what are the only 2 high intensity statins and what are the doses
atorvastatin 40-80mg
rosuvastatin 20-40mg
major AE of statins
what can it progress to?
MYOPATHY - mild muscle soreness or weakness
can progress to life-threatening rhabdomyolysis (muscle breakdown)
another AE of statins aside from myopathy
hepatotoxicity (rare)
true or false
statins are CI in pregnancy
true
if a patient is trying to get pregnant, should they continue taking the statin until they are confirmed pregnant?
NO
should stop prior to conception
2 AE of statins aside from myopathy/rhabdo and hepatotoxicity
cognitive SE (nerologic - rare)
hyperglycemia - can cause diabetes!
what test can be done to monitor a patient’s liver function while they are on a statin
transaminase testing (AST/ALT)
true or false
statins commonly interact with fibrates
true - esp gemfibrozil
name 3 drugs that may increase the risk of statin-induced myopathy
niacin
protease inhibitors (HIV)
amiodarone
what was the first statin
lovastatin
true or false
lovastatin does not contain a lactone ring
FALSE - it does. it is a prodrug and hydrolyzed in vivo
true or false
CYP3A4 inhibitors taken with lovastatin increases the risk of myopathy
true
interaction between cyclosporine + lovastatin
cyclosporine inhibits the OATP1 transporter
therefore, lovastatin levels will increase in the blood
true or false
atorvastatin is not a prodrug
true
when should atorvastatin be discontinued
if symptoms of renal failure or myopathy due to rhabdomyolysis develop
2 monitoring parameters for atorvastatin (and really all statins)
liver function test (hepatotoxicity)
creatine kinase (elevated levels indicate muscle damage!)
