Test 1: Wk2: 1 Antilipemics - Velentovic Flashcards
Acceptable cholesterol level
<200
Acceptable LDL-C level
<100
Acceptable Triglyceride level
<150
Hyperlipidemia primary causes (2)
diet and genetics
Hyperlipidemia secondary causes (2)
drugs
certain diseases and conditions (diabetes and alcoholism)
1st Line of therapy
diet
decreasing total daily — intake will help cholesterol and triglyerides
fat
high triglycerides are caused by — reduce them by decreasing intake of — and —
high carb intake
carbs and alc
increasing exercise increases — levels
HDL
5 Drugs that lower Cholesterol
resins Statins Nicotinic Acid Ezetimibe PCSK9 Inhibitors
what are the 3 resins
Cholestyramine
Colesevelam
Colestipol
the bioavailability of statins is — why?
0; not absorbed in GI
Normally bile acids undergo —
recirculation 6x/day blocked by —
Normally bile acids undergo enterohepatic
recirculation 6x/day blocked by resins
resins cause increased — excretion of —
fecal; bile acids
resins increase conversion of hepatic — to —
cholesterol to bile acids
bile acids have a negative feedback on — and — remove this negative feedback
7a hydroxylase
resins
resins increase number of — receptors
hepatic LDL
increased hepatic LDL receptors causes a compensation for — resulting in —
compensation for decreased intrahepatic
cholesterol
lower plasma LDL-C
resins are used to treat
hypercholesterolemia
how long for resins to have maximal effects
4 weeks
resins decrease LDL-C by — %
20
resins are often combine with (4 drugs)
HMG CoA reductase inhibitors
ezetimibe
fibrates
Nicotinic acid
can resins be used in pregnant women and children
yes
children older than 6
where do the major side effects of resins occur and what are they
GI
bloating and constipation
what is taken with resins to lessen side effects
Colesevelam
resins interfere with —
fat sol vit and drugs
how much should resin dosing be staggered
1 hr before
4 hrs after
HMG CoA Reductase Inhibitors are also known as
Statins
what are the 7 statins
Atorvastatin , Simvastatin , Lovastatin, Rosuvastatin Pravastatin, Fluvastatin &
Pitavastatin
Statin are a — inhibitor of — enzyme in — biosynthesis
competitive, HMG CoA reductase; cholesterol
Statin site of action is primarily in
the liver
Statins increase the number of — and increase the clearance of —
hepatic LDL receptors
plasma LDL
Statins are used to lower
cholesterol
what 2 statins are used to lower cholesterol and triglycerides
Atorvastatin and Rosuvastatin
Statins elevate — and —
plasma ALT/AST
CPK
Statins increase risk of — and —
hepatic and renal disease
the risks of statins — with — dose
increase with higher dose
increased CPK is associated with —
myalgia
what to statins have the least side effects
fluvastatin and pravastatin
3 Statin contraindications
Pregnancy X
Nursing mothers
Acute Liver Dz
max effect of statins takes
2 weeks
statins increase — levels
HDL
statins have — absorption and — bioavail
good, low
What statin can be used in pediatrics (8 yrs)
pravastatin
Age 10+ for other statins
peak cholesterol synthesis is from — to —
midnight to 2 am
what 3 statins are taken at night
Fluvastatin , Lovastatin, Simvastatin
what 3 statins can be taken any time of day
Atorvastatin, rosuvastatin and pravastatin taken
what 2 statins bioavail is lowered by food
Pravastatin & Pitavastatin
why do Atorvastatin and
Rosuvastin reduce
cholesterol and triglycerides
(3 reasons)
loner t1/2
higher increase in LDL receptors
increase clearance of IDL
— and — statins are prodrugs and are converted to active metabolites by — and —
Lovastatin and Simvastatin
intestinal carboxylesterase and CYP3A4
— is the substrate for atorvastatin, lovastatin
and simvastatin
CYP3A4
avoid grapefruit juice with
atorvastatin, lovastatin
and simvastatin
— rosuvastatin and fluvastatin
CYP2C9 rosuvastatin and fluvastatin
— simvastatin
CYP2D6 simvastatin
simvastatin induced — is higher with — allele
muscle pain; CYP2D6*4
— SNP lowers hepatic
uptake, higher plasma levels
SCLO1B1 SNP (OATP1B1) lowers hepatic uptake, higher plasma levels
Ezetimibe inhibits — absorption at the —
cholesterol; brush border of SI
Ezetimibe inhibits Inhibits cholesterol absorption at —
enterocytes
Ezetimibe inhibits —transporter protein
NPC1L1
Ezetimibe targets
dietary cholesterol
Ezetimibe lowers LDL-C by max — %
20
Ezetimibe works better when combined with – instead of doubling — dose
statin; statin
Ezetimibe adverse effects and what is most common
minimal GI
diarrhea most common
don’t use Ezetimibe with
hepatic dysfunction
Ezetimibe increases risk of elevated — when combine with
transaminase; statins
Ezetimibe not often combined with
resins
2 PCSK9 Inhibitors
Alirocumab and Evolocumab
PCSK9 inhibitors MOA
bind LDL receptor and degrades it
less LDL can be removed from blood
By inhibiting PCSK9, more LDL receptor can remove more LDL
Alirocumab and Evolocumab are used with
statin or ezetimibe
Alirocumab and Evolocumab dosig
every 2 wks sub Q
Alirocumab and Evolocumab decrease — by —% when combined with —
LDL-C 50-70% Ezetimibe
Alirocumab and Evolocumab side effects
allergy
3 Drugs that lower triglycerides
Fibrates
Nicotinic Acid
Omega-3-Acid Ethyl Esters
2 FIbrates
Gemfibrozil and Fenofibrate
Fibrates bind — to stimulate —
PPARa; FA oxidation
fibrates reduce — expression resulting in increased — activity
apoCIII
lipoprotein lipase
Fibrates decrease hepatic production of — by increasing —
VLDL; clearance
fibrates increase — by —%
HDL; 15%
increased risk of gallstones is only associated with which fibrate
clofibrate
fibrates have an increased risk of — when combined with —
myopathy; HMG CoA reductase inhibitors
myopathy is worse with what fibrate
Gemfibrozil
Gemfibrozil inhibits —
OATP2
risk of myopathy is least with what fibrate
fenofibrate
fibrate contraindications (3)
liver dysfunction
renal dz
gallbladder dz
Nicotinic Acid decreases production of —
hepatic VLDL
Nicotinic acid inhibits — decreasing delivery of — to the —
lipolysis
FFAs
liver
Nicotinic acid inhibits — in -fat cells decreasing circulation of —
hormone sensitive lipase
FFAs
increased — increases — clearance
lipoprotein lipase; VLDL
Nicotinic acid does not interact with
PPARa
Nicotinic acid lowers
TG and Cholesterol
Nicotinic acid adverse effects (3)
itching, flushing
increased ALT/AST
what needs to be monitored when Nicotinic acid is combined with satins
creatine kinase
Nicotinic acid should not be used in pts with
peptic ulcer
Nicotinic acid may cause — and —
hyperuricemia and glucose intolerance
Nicotinic acid contraindications
bleeding disorder
liver dz
peptic ulcer
Icosapent Ethyl lowers — in individuals with —
TGs, high >500 mg/dl TG
Icosapent Ethyl inhibits
DGAT
Icosapent Ethyl decreases — synthesis
VLDL
Icosapent Ethyl increases —
lipoprotein lipase eicosapentatonic acid
Icosapent Ethyl adverse effects
arthralgia
Icosapent Ethyl contraindications
hypersensativity
Familial hyperchylomicronemia Type 1 has elevated — and —
chylomicrons and TGs
Familial hyperchylomicronemia Type 1 has defect in
lipoprotein lipase or Apo CII
Familial hyperchylomicronemia Type 1 control
diet therapy
fibrates and nicotinic acid
Familial hypercholesterolemia IIa elevated — and —
cholesterol and LDL
Familial hypercholesterolemia IIa increased risk for
CVD
Familial hypercholesterolemia IIa decreased clearance of
LDL
Familial hypercholesterolemia IIa tx
resins
statins, ezetimibe combined with PCSK9
Familial hypercholesterolemia IIb elevated — and —
VLDL and LDL
Familial hypercholesterolemia IIb tx
Statins and Nicotinic acid
Familial dysbetalipoproteinemia III elevated — and —
TGs and Cholesterol
Familial dysbetalipoproteinemia III — and — remnants
IDL and chylomicron
Familial dysbetalipoproteinemia III presence of abnormal
Apo E - E2
Familial dysbetalipoproteinemia III increased — production
VLDL
Familial dysbetalipoproteinemia III most sensitive to
fibrates
50% TG redcution
Familial hypertriglyceridemia IV elevated — and —
TG and VLDL
Familial hypertriglyceridemia IV associated with — and or —
hyperuricemia and glucose intolerance
Familial hypertriglyceridemia IV tx
fibrates
nicotinic acid
Diseases cholesterol elevated in
biliary dz
renal dz
hypothyroidism
diabetes
Diseases Triglycerides elevated in
alcoholism
renal dz
diabetes
thiazide diuretics elevated — and — by —%
cholesterol and TGs by 10-15%
Beta Blockers elevate — and decrease —
TG and HDL
oral contraceptives elevate
TGs
