Week 4 (Exam 1) Flashcards
Statin Lipid Lowering MOA
blocks HMG CoA Reductase to mevalonic acid
Statin Inflammation reducing MOA
Reduces CRP and Erythrocyte Sedimentation Rate
Statin Reversal of Endothelial Dysfunction MOA
Increase in NO synthesis Reduced oxidized LDL Inhibition of Endothelin synthesis Reduction in Endothelial Permeability to LDL cholesterol Inactivation of Superoxide
Statin Decreased Thrombogenicity MOA
Reduced endothelial and atherosclerotic plaque macrophage tissue factor expression
Decreased Prothrombin activation and thrombin generation
Improved fibrinolysis
Decreased platelet activation
Advicor
Lovastatin and Niastatin
XR
Simcor
Simvistatin and Niastatin
XR
Vytorin
Simbistatin and Ezetimibe
Muscle related side effects of Statin
Bilateral, symmetrical, skeletal muscle myopathy
No rise in Creatine Kinase
How do statins cause liver damage?
Temporary depletion of intracellular cholesterol causes an increase in LDL receptor production
Statins and transaminase levels
Asx and dose-related increases 3x normal
ALT > AST (distinguishes liver from muscle AST)
All statins have been show to cause…
AKI (rhabdomyolysis, subsequent myoglobinemia)
The two pro-drug Statins
Simvistatin and Lovastatin (increases their hepatic metabolism)
Statins that should maybe be given at a lower dose for asian populations
Rosuvastatin and Simvastatin
Statins metabolized in CYP3A4 pathway
Atorvastain
Simvastatin
Lovastatin
Statins metabolized in CYP2C9
Fluvastatin
Ezetimibe MOA
Inhibits dietary and biliary cholesterol absorption at brush border via NPC1L1 so Liver has to then take more from the circulation
Also blocks chostesterol traffickers Aminopeptidase N and Cave-in 1-Annexin A2 Complex
NPC1A1
Expressed in Intestine and Liver as Sterol Transporter to mediate intestinal cholesterol absorption and counterbalances hepatobiliary cholesterol excretion
Inhibited by Ezetimibe
Indications for Ezetimibe
Homozygous Familial Hypocholeterolemia
Homozygous Sitosterolemia
Primary Hyperlipidemia
Ezetimibe dosing for Homozygous Familial Hypercholesterolemia
10mg PO qDay w/ Atorvastatin or Simvastatin
Ezetimibe dosing in Primary Hyperlipidemia
10mg PO qDay w/ HMG-CoA Reductase inhibitors in diet
Can be monotherapy
can be w/ fenofibrate
can be w/ Statins
Contraindications of Ezetimibe
Pregnancy and breastfeeding when combo w/ statin
Hepatic Disease or impairment
Toxicity of Ezetimibe
Skeletal muscle toxicity when used with statin, especially over 65 y.o., hypothyroidism, renal impairment
PCSK9 Inhibitor MOA
Serine Protease: cleaves LDL receptors at Serine Residues (degrades them)
Increases Hepatic LDL-R and Decreases Plasma LDL-C
The two PCSK9 Inhibitors
Alirocumab and Evolocumab
Indications for Alirocumab and Evolocumab
PCSK9 Inhibitors: Tx FH and Atherosclerotic CVD
Most common PCSK9-I side effects
Runny nose, sore throat, injection site rxn
Bile Acid Sequestrant MOA
Not absorbed, but bind bile acids and are excreted as a complex
Cholesterol depletion increases LDL rec Activity (increases removal of LDL cholesterol from blood)
Bile Acid Sequestrants (3)
Colesevelam, Colestipol, Cholestyramine
Contraindications of Bile Acid Sequestrants
Its with Dysbetalipoproteinemia: induced Pancreatitis
Decreased GI Motility
Adverse Effects of Bile Acid Sequestrations
Elevated TAGs
Elevated Liver Enzymes
Vit D Deficiency
Bile Acid Sequestrant Warnings and Precautions
ADEK and Folic Acid Deficiency
Phenylketonuria (contains F)
Fibrate MOA
PPARa Activator: Increases liver enzymes for TAG metabolism and uptake
Fenofibric Acid (Fibrate) Indications
Dyslipidemia
Severe HyperTAG-emia
Gemfibrozil (fibrate) Indications
Severe HyperTAG-emia
Primary Prevention of Coronary Heart Disease (in type IIb patients)
Gemfibrozil Drug Contraindications
Dasabuvir Repaglinide Simvastatin (muscle toxicity with statins) Cerivastatin Enzalutamide (increases seizure risk) Selexipag
Gemfibrozil Side Effects
GI: stomach pain, nausea
Increased liver enzymes (same with other Fibrates)
Elevated Creatinine Kinase (like other Fibrates)
Gallstones (like other Fibrates), maybe.
Myopathy and Rhabdomyolysis (like other Fibrates)
Kidney and Liver Dz
Fibrates and GFR
Do not use if GFR is below 30 ml/min
GFR between 30 - 59? Keep dose below 54 mg/day
Why can Fibrates cause a slight increase in serum creatinine?
They inhibit kidney Organic Cation Transporter 2
Gemfibrozil is a strong inhibitor of:
CYP2C8
Bile Acid Sequestrants and Fibrates
Can interfere with Fibrates (take 1 hour before or 4 hours after BAS)
Colchicine + Fibrates
Muscle Toxicity, Rhabdomyolysis
Fibrates + Ezetimibe
Fibrates increase the levels of Ezetimibe
Fibrates + Warfarin
Fibrates interfere with the warfarin
Fibrates + Cyclosporine / Tacrolimus
Nephrotoxicity
OAT1B1
Inhibited by Gemfibrozil (hepatic uptake transporter)
Fibrates in pregnancy
Idk, but definitely don’t use them while nursing
Niacin MOA
Maybe increase lipoprotein lipase
Maybe inhibits release of free fatty acids from adipose
Maybe decreases rate of LDL/VLDL synthesis
Indications for Niacor
Reduction of total and LDL Cholesterol
Adjunct therapy for adults wit super high TAGs
Indications for Niaspan
To increase HDL
To reduce total cholesterol, LDL, Apo B, TAGs
Niacin Adverse Effects
Flushing, itching
Blood sugar elevation
Raise Uric Acid Levels, liver enzymes
Niacin warnings and precautions
Don't use with Liber Disease Can raise blood sugar: don't use with diabetes Can increase uric acid levels (gout) Can prolong bleeding time Contraindicated in PUD
Niacin metabolism
CYP2D6 Inhibitor
Drug interactions with Niacin
Statins and Bile Acid Sequestrants
