anti-hyperlipidemics #2 Flashcards
HMG-CoA Reductase Inhibitors
indications: hypercholesterolemia: elevated ___ with slightly elevated ___
- standard practice to initiate immediately after ___, irrespective of lipid levels
Expected results
- 20-60% reduction in ___
- 10-33% reduction in ___
- 5-10% increase in ___
LDL, TG
- MI
- LDL
- TG
- HDL
HMG-CoA Reductase Inhibitors
short half life preparations are given in the ___ to inhibit ___ cholesterol synthesis
___ , ___ IR , and ___ IR are given PM
evening, nocturnal
- simvastatin, lovastatin, fluvastatin
HMG-CoA Reductase Inhibitors - Metabolism
CYP 3A4: ___ , ___ , and ___
- tend to accumulate in presence of drugs that ___ or ___ for CYP3A4: ___ antibiotics, cyclosporine, ___, grapefruit juice
CYP2C9: ___ and ___
- inhibitors may increase plasma levels: cimetidine, ___ , ___
Sulfation: ___ , but most is excreted unchanged
___ is mainly excreted unchanged in bile, undergoes ___ recirculation
lovastatin, simvastatin, atorvastatin
- inhibit, compete
- macrolide, ketoconazole
- metronidazole, amiodarone
- pravastatin
- pitavastatin, enterohepatic
HMG-CoA Reductase Inhibitors
Adverse effects: skeletal muscle effects
rhabdomyolysis ( ___ ) with ___ dysfunction secondary to ___
- ___ related
- monitor serum creatine ___ (CPK)
- increased incidence when co-administered with CYP inhibitors; may occur with ___
Hepatotoxicity
- monitor serum ___ activity
- less than 2% incidence (underlying liver disease or alcohol abuse)
Increased incidence of ___
- myopathy, renal, myglobinuria
- dose
- phosphokinase
- gemfibrozil
- transaminase
- T2DM
T2DM due to reducing cholesterol in membrane of pancreatic B cells
ATP-Citrate Lyase Inhibitor (ACL)
Bempedoic acid (Nexletol)
- dosing: PO once daily adjunct to statins
- ACL is an enzyme ___ of HMG-CoA reductase in the cholesterol synthetic pathway
- reduces serum ___ and ___ levels when added to statin therapy in patients with ___ ___ ___ (HeFH) or established ___ ___ ___ (ASCVD)
- metabolized by ___ , excreted via kidneys
- inhibits ___ in renal tubules - may cause hyperuricemia and ___
- upstream
- LDL, TC, heterozygous familial hypercholesterolemia, stherosclerotic cardiovascular disease
- glucuronidation
- OAT2, gout
PCSK9 Inhibitors
proprotein convertase subtilisin kexin type 9 (serine protease)
- promotes degradation of ___ in the ___
- MOA: increase LDLR # and reduce ___ levels
- ____ (Praluent) - inj SQ q ___ weeks
- ___ (Repatha) - inj SQ q ___ weeks or once a month
- adjunct to diet and max tolerated statin in patients with ___ , ___ , and ___
- LDL receptors, liver
- LDL
- alirocumab
- evolocumab
- ASCVD, HeFH, HoFH
PCSK9 Inhibitors
Inclisiran (Leqvio)
___ - hybridizes PCSK9 ___ and directions degradation in hepatacytes
- lowers ___ cholesterol
- injected SQ at ___ then ___ month intervals
- used adjunct to statins in ___ and ___
- adverse effect: inj site rxn ___
siRNA, mRNA
- LDL
- 3, 6
- HeFH, ASCVD
- arthralgia
Inhibitirn g Apo B Lipoprotein synthesis - Juxtapid (Lomitapide)
small molecule microsomal TG transfer protein (MTTP) inhibitor
- inhibits assembly of Apo ___ containing lipoproteins in ___ and ___
- interferes with ___ and ___
- given PO daily with increases q ___ weeks to max dose
- indicated as adjunct to other treatments from patients with ___ familial hypercholesterolemia LDLR mutation
- high risk of ___ damage (restricted rx program)
- B
- liver, intestine
- 2
- homozygous
- liver
Juxtapid (Lomtapide) mechanism of action
T or F: mechanism does not require LDL-R
True
Apo B
Inhibitirn g Apo B Lipoprotein synthesis - mipomersen (Kynamro)
phosphororthioate ___ oligonucleotide inhibitor of Apo ___
- hybridizes Apo ___ in liver and promotes degradation
- very ___ synthetic oligonucleotide, injected SQ once weekly
- indicated as adjunct to other treatments for patients for ___ familial hypercholesterolemia
- ___ risk of liver damage - (restricted rx program, hepatic steatosis)
- antisense, B100
- mRNA
- stable
- homozygous
- high
Inhibiting Angiopoietin-like protein 3
Evinacumab-dgnb (Evkeeza)
- IV infusion once/month
- treatment of ___ familial hypercholesterolemia
- increases ___ lipase (LPL) and ___ lipase (EL) activity by preventing ANGPTL3 mediated inhibition. Lowers ___ cholesterol
- does NOT require ___
-homozygous
- lipoprotein, endothelial
- LDL
- LDL-R
Fibric Acid Derivatives
peroxisome proliferator-activated receptor alpha activators (PPARa)
- fibrates bind to ___ and regulate gene transcription along with the retinotic aid receptors (RXR). Effects are complicated
- derivates of a branched chained ___ acid known and fibric acid (fibrate)
- 2 main examples
- ___ must undergo bioactivation to fenofibric acid
reduce ___ 6-20%
reduce ___ 35-53%
elevate ___ 15-30%
- carboxylic
- fenofibrate, gemfebrozil
- fenofibrate
- LDL
- TG
- HDL
Fibric acid derivatives
indications:
- ___ in which ___ predominates
- second line drug for mixed ___
side effects:
- gall stones (cholelithiasis)
- skeletal muscle effects - rhabdomyolysis (use with caution with ___ )
drug interactions
- potentiate effects of ___
- hypertriglyceridemia, VLDL
- hyperlipidemia
- statins
- warfarin
Niacin
- Vitamin at dietary levels (no effect on lipids)
- high doses ( ___ - ___ g/day) lowers serum lipids
MOA: reduces serum ___
- increases ___ activity to increase clearance of ___
- decrease hepatic ___ production
- may significantly reduce ___ and ___
- usually increases ___ levels
- 1-3 g/day
- triglycerides
- lipase, VLDL
- VLDL
- LDL, TG
- HDL
Niacin Targets
- Adipose - inhibits ___ lipolysis by hormone-sensitive lipase: decreasing ___ transport to liver. Via activation of ___
- Liver - inhibits ___ synthesis and esterification: reducing ___ export via VLDL
- Macrophages - increases expression of ___ and ___ : decreasing CE content via HDL-medicated ___ transport
- FA, GPR109A
- FA, TG
- CD36, ABCA1, reverse
Omeqa-3-fatty acid ethyl esters - NUTRIENTS
combination of ___ ___ of omega-3-fatty acid
- MOA: reduce synthesis of ___ in liver: omega-3 fatty acids are ___ substrates for enzymes responsible for ___ synthesis
- EPA + DHA: ___ and ___
- EPA only: ___
ethyl esters
- TG, poor, TG
- Lovaza, Omtryg
- Vascepa
