SEARCH RESULTS FOR: Pharmacotherapy-for-Dyslipidemia-Overview

Pharmacotherapy for Dyslipidemia Overview

Pharmacotherapy for Dyslipidemia: General overview Dyslipidemia Authors: Rupali Manek Reviewers: Gurreet Bhandal, Raafi Ali, Yan Yu*, Samuel Fineblit* *MD at time of publication Hypolipidemia (↓ HDL or ↓ apoB containing lipoproteins like LDL) Bile-acid sequestrants Bind bile acids in intestinal lumen to prevent reabsorption by enterohepatic (gut-liver) circulation ↑ Excretion of bile acids and cholesterol in stool ↓ LDL in blood Side effects: GI disturbances, commonly interact with other drugs by interfering with absorption See Calgary guide slide on “Bile-acid sequestrants: Mechanisms of action & side effects” for complete description of mechanism and side effects (clinical imbalance of lipids) Hypertriglyceridemia (if VLDL mediated & in need of treatment for pancreatitis prevention) Hypercholesteremia (↑ LDL in blood) Ezetimibe Inhibits cholesterol absorption via NPC1L1 transporter ↑ Hepatic (liver) LDL receptor expression ↑ LDL clearance from blood ↓ LDL in blood Avoid in pregnancy See Calgary guide slide on “Ezetimibe: Mechanisms of action & side effects” for complete description of mechanism and side effects Combined hyperlipidemia (↑ Triglycerides and ↑ cholesterol) Statins (ex. rosuvastatin, atorvastatin, simvastatin, pravastatin) Competitive inhibitors of HMG-CoA reductase (rate-limiting enzyme in cholesterol synthesis) Fibrates (ex. fenofibrate, gemfibrozil) Activate PPAR! (nuclear receptor) ↑ Lipolysis (breakdown of lipids) and free fatty acid oxidation ↓ Triglycerides in blood Side effects: GI discomfort, rash, pruritis Contraindicated in pregnancy, renal failure, liver & gallbladder disease See Calgary guide slide on “Fibrates: Mechanisms of action & side effects” for complete description of mechanism and side effects PCSK9 inhibitors (ex. evolocumab and alirocumab which are monoclonal antibodies) Inhibit PCSK9 (holds the LDL:LDL receptor complex together as it is internalized into the cell for destruction of LDL) LDL receptor returns to surface without being destroyed ↑ LDL receptor expression ↑ LDL clearance from blood ↓ LDL in blood See Calgary guide slide on “PCSK9 Inhibitors: Mechanisms of action & side effects” for complete description of mechanism and side effects ↓ Cholesterol synthesis in liver ↑ LDL receptor expression in liver LDL receptor recognizes apoB100 (structural protein on LDL) and apoE (structural protein found on chylomicron, VLDL, IDL) ↑ Clearance of LDL cholesterol from bloodstream ↓ LDL cholesterol in blood ↑ HDL in blood ↓ Triglycerides in blood ↓ Atherosclerosis (plaque along walls of blood vessels) Abbreviations: HDL – High density lipoprotein; HMG-CoA – Hydroxymethylglutaryl- CoA; LDL – Low-density lipoprotein; PCSK9 – Proprotein convertase subtilisin/kexin type 9; PPAR! – Peroxisome proliferator-activated receptor alpha; NPC1L1 – Niemann-Pick C1-Like 1; VLDL – Very low-density lipoprotein Side effects: Myalgias (muscular aches), rhabdomyolysis (muscle breakdown), transaminitis (liver inflammation), liver failure, ↑ risk of diabetes mellitus Contraindicated in pregnancy See Calgary guide slide on “Statins: Mechanisms of action & side effects” for complete description of mechanism and side effects Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications Published Nov 6, 2023 on www.thecalgaryguide.com