HMG COA Reductase Inhibitors PDF

## HMG COA Reductase Inhibitors - **Drugs:** - Atorvastatin - Fluvastatin - Rosuvastatin - Atorvastatin and rosuvastatin are high intensity statins - Lovastatin - Simvastatin - Pitavastatin - Pravastatin - **MOA:** - Active form of the analog of HMG-COA inter...

## HMG COA Reductase Inhibitors - **Drugs:** - Atorvastatin - Fluvastatin - Rosuvastatin - Atorvastatin and rosuvastatin are high intensity statins - Lovastatin - Simvastatin - Pitavastatin - Pravastatin - **MOA:** - Active form of the analog of HMG-COA intermediate - Competitive/ reversible inhibitors - Increase in high affinity LDL receptors (liver) lead to decrease in blood LDL level - **ADR/ Contraindications:** - Hepatotoxic - Myopathy - DO NOT USE IN PREGNANCY - Rhabdomyolysis (protein breakdown in the muscle) - **D-D:** - Fibrates - Gemfibrozil - Cyclosporine - Digoxin (more with atorvastatin) - Warfarin - Macrolide antibiotic - Azole antifungal - Statin induce myopathy - niacin - HIV protease inhibitor - Amiodarone - Nefazodone - Grapefruit juice - **PK:** - Extensive 1st pass hepatic uptake (OATPI BI) on all of the statins - Atorvastatin & simvastatin should be taken in PM (t1/2 of 4h or less) - Fluvastatin and pravastatin have some HMG-CoA reductase inhibitory - In plasma statins and their metabolites are highly protein bound - Majority of the statin metabolites are excreted through the liver, and eliminated through poop and urine - **Metabolism:** - SAL- CYP3A (sim, ator, lov) - Rosuvastatin-CYP2C9, 2C19 - Fluvastatin- CYP2C9 - Pitavastatin- glucuronide (UGTIA3 & UGT2B7) - Pravastatin- largely unchanged **** ## Bile Acid Binding Resins - **Drugs:** - Colestipol - Cholestyramine - Colesevelam - **MOA:** - They are anion exchange resins - Bile acid sequestrant are highly positively charged and bind negatively charged bile acid (+ bind to -) - Resins are not absorbed, and the bound bile acids are excreted in the stool - Low bile acid, liver bile acid starts to increase bile acid - Liver cholesterol content declines, stimulating the production of LDL receptors - Increase liver triglyceride synthesis - **ADR/ Contraindications:** - Hyper cholemic acidosis - Severe hypertriglyceridemia - Gl uncomfortable - Heartburn - Diarrhea - Malabsorption of vitamin K (fat soluble vitamin) - **D-D:** - This class will interact with any drug that's acidic **** ## Fibrates: **PPAR-alpha** - **Drugs:** - Gemfibrozil - Fenofibrate *prodrug* - **MOA:** - Ligand agonist for PPAR-a - Transcriptional effect→ Increase LPL, apo A and apo A-II - Stimulation of fatty acid oxidation increase LPL synthesis and reduce expression of apo C-III - Combination with statin better - **ADR/ Contraindications:** - Myopathy - Liver toxicity - **D-D:** - Reductase inhibitor increase myopathy effect - Coumarin anticoagulant - All of those four-cause interaction with myopathy: - Colchicine - Statin - Amiodarone - Niacin - **PK:** - Non-metabolized - Tightly bound to plasma protein - Undergoes enterohepatic circulation and readily passes the placenta - Eliminated through the kidney, mostly unmodified - **Metabolism:** - Avoid in patient with hepatic and renal dysfunction - **Gemfibrozil** has a higher chance of myopathy compared to fenofibrate - **Fenofibrate**, are more effective than gemfibrozil at increasing HDL level **** ## Sterol Absorption Inhibitors - **Drugs:** - Ezetimibe - **MOA:** - Inhibit intestinal absorption of phytosterol and cholesterol by inhibiting the transport protein NPCILI - Inhibits cholesterol synthesis - They are Noncompetitive - Used as a combination with statins (gives a synergic effect) - Ezetimibe are extrinsic and statins are intrinsic - **ADR/ Contraindications:** - Rare allergy - **D-D:** - **PK:** - Highly water soluble - Glucuronidated in the epithelium and absorbed then entered an enterohepatic recirculation - **Metabolism:** - It will still work even if you're not eating cholesterol **** ## PCSK9 antibody "the mabs" given SQ - **Drugs:** - Evolocumab - Alirocumab (brand name Repatha) - **MOA:** - They are monoclonal antibody - They are the protease that binds to the LDL receptor on the surface of the liver cell - Enhance lysosomal degradation of the LDL receptor decrease of LDL in the blood - "Its just this PCSK9 is a antibody that blocks the PCSK9 protein that our body makes so more liver cells with the LDL receptor will bind more to the LDL molecule from the blood which then meet our ultimate goal which is lowering cholesterol" - **ADR/ Contraindications:** - NOT use in pregnancy or breastfeeding - NO myopathy issue - Injection site reactions - **D-D:** - **PK:** - **Metabolism:** - **Given with statins cause synergistic effect by increasing number of LDL receptors** **** ## Niacin (Nicotinic acid) another word for vitamin B3 - **Drugs:** - Niacin - **MOA:** - Decrease VLDL and LDL production → Increase HDL - Adipose tissue: inhibits the lipolysis of triglycerides by lipase, decrease transport of free fatty acid to liver and decreasing hepatic triglyceride - Liver: reduce triglyceride synthesis by inhibiting both the synthesis and ethe esterification of fatty acid - Niacin: enhance LPL activity (promote the clearance of chylomicrons and VLDL triglycerides)→ raise HDL levels by decreasing apo-a in HDL - **ADR/ Contraindications:** - Flushing (skin becomes red) - Dyspepsia (rare nausea) - Hepatotoxicity - Arrythmias - **D-D:** - Combination with resin or reductase inhibitor cause myopathy - **PK:** - Dose needed generally higher than as a vitamin - Very short half-life so given 2-3 times per day - Excreted unchanged or only major metabolite nicotinic acid - Found in the urine - **Metabolism:** **** ## OMEGA 3- fatty acid ethyl esters (fish oil) - **Drugs:** - Fish oil (OTC) - High dose of it is RX - **MOA:** - Act on PPAR-a and stimulate expression of PPAR dependent genes - Reduce VLDL triglycerides - Used as a supporting agent treatment for patient with severe hypertriglyceridemia - **ADR/ Contraindications:** - Fishy burps - Increased LDL - **D-D:** - Prolonged bleeding patient taking anticoagulant should be monitored - **PK:** - **Metabolism:**