Midterm Flashcards
Pharmacology
Kinectics of Statins
Extensive first-pass hepatic uptake (OATPIBI)-> (organic anion transporter protein 1B1)
Lovastatin
First statin
Metabolized by CYP3A4
DDI- CYP3A4 inhibitors increase risk of myopathy
Reductace inhibitors MOA
Competitive/reversible inhibitors
Increase in high-affinity LDL receptors (liver)-> decrease blood LDL levels
Mechanism is transcription
Reduces Rho and Rab proteins (leads to blood vessel relaxation)
Atorvastatin
Lipitor
With food AM or PM (better in evening)
Metabolism- CYP3A4
Half life 14 hrs
Monitor- Liver Function test (LFT) and Creatine Kinase (SCR)
AE and DDI of lipitor
AE- Myalgia
Discontinue if symptoms of renal failure or myopathy due to rhabdomyolysis develop
DDI- Gemfibrozil, Niacin-> myopathy
Simvastatin
Zocor
Very potent 5mg-40mg daily
Monitor- Liver function test (LFT) and signs of myopathy
Pravastatin
Pravachol
Should be given either 1 hr or more before or at least 4 hrs following resin
Not a prodrug
Rosuvastatin
Crestor
Use low doses with gemfibrozil and cyclosporine
AE and caution of crestor
AE - Myalgia
Caution- Renal failure may predispose to rhabdomyolysis, increase INR with concurrent warfarin (due to CYP2C9), heavy alcohol drinkers, Liver disease, proteinuria, Japanese/Chinese- predisposition to myopathy
Pitavastatin
Livalo
CI drugs- fibrates, cyclosporine
Does not affect warfarin’s effect (no increase in bleeding risk)
MOA of Bile acid binding resins
MoA
Oldest/safest because it does not get absorbed into blood
The bile acid sequestrants are highly positively charged and bind negatively charged bile acids Increases hepatic bile acid synthesis and hepatic triglyceride synthesis
Decreases LDL by stimulating the production of LDL receptors, similar to statins
AE of Bile acid binding resins
Chloride salts-> hyperchloremic acidosis, Severe hypertriglyceridemia is a CI (because they increase triglyceride levels), CI in diverticulitis, Malabsorption of vitamin K (clotting issues)
DDI with all anionic drugs
MOA of fibrates
PPAR- Alpha (agonist) activation induces fatty acid oxidation/ lipoprotein lipase
Have antithrombotic effects
PK of gemfribozil and fenofibrate
Gemfibrozil (does not undergo change), Fenofibrate (undergoes hydrolyzation-> has ester) Gemfibrozil- undergoes enterohepatic circulation, and eliminated through kidneys mostly unmodified
Fenofibrate- isopropyl ester prodrug that is hydrolyzed completely in the intestine
Thera of Fibrates
Useful for hypertriglyceridemia
Feno is more effective than gem at increasing HDL
Not much effect on LDL-C
Feno is the fibrate of choice for combo with a statin
AE of fibrates
Rashes, Myopathy (gem more than feno), Liver toxicity
Risk of Myopathy increases when given with statins
Avoid fibrates if pts have hepatic or renal dysfunction
Increase risk of cholithiasis (gallstones) when administered with ezetimibe Caution- coumarin anticoagulant
MOA of Ezetimibe
Allosteric Non-competitive inhibitor of NPC1L1
Inhibits intestinal absorption of phytosterols and cholesterol
Inhibits cholesterol uptake by inhibiting the transport protein NPC1L1
PK of Ezetimibe
Highly water insoluble
Glucuronidated in the intestinal epithelium
Excreted in the feces
Thera of Ezetimibe
Monotherapy- used in statin intolerant pts
Synergistic with statin for dyslipidemia
Useful for phytosterolemia
AE of Ezetimibe
Low chance for causing myopathy
Bile acid sequestrants inhibit absorption of ezetimibe and should not be administered together
What are the PCSK9 antibodies and their MOA
Proprotein convertase subtilisin/ kexin type 9 is a protease that binds to the LDL receptor on the surface of hepatocytes and enhances lysosomal degradation of the LDL receptor, resulting in higher plasma LDL concentrations which decreases LDL levels