Pharmacology II - Treatment of Hyperlipidemia PDF

MIDTERMS PHARMACOLOGY II LECTURE UNIT 4: TREATMENT OF HYPERLIPIDEMIA OUTLINE ▪ type of fat trans...

MIDTERMS PHARMACOLOGY II LECTURE UNIT 4: TREATMENT OF HYPERLIPIDEMIA OUTLINE ▪ type of fat transported in the bloodstream I. DEFINITION oHyperchylomicronemia II. TYPES OF MAJOR GENETIC HYPERLIPIDEMIA III. PHARMACOLOGIC TREATMENT OF ▪ Elevated levels of chylomicrons HYPERLIPIDEMIA o Chylomicron ▪ Responsible for the transport of CORONARY HEART DISEASE exogenous cholesterol and TG from the Leading cause of death worldwide small intestine to the tissues after meals ↑LDL & triglycerides; ↓ HDL in blood serum (since it is an exogenous transported there High total cholesterol and highly elevated LDL will be a high TG, cholesterol in the body) High total cholesterol– sum of LDL, VLDL and HDL ▪ Chylomicron in Some laboratory results ↑HDL – associated with ↓ risk of heart disease are not detected in TG and cholesterol) TREATMENT: LDL: “bad” cholesterol - carries cholesterol from the o Low-fat diet liver to the cells that need it for various functions, o No drug therapy is effective for Type I such as building cell membranes. HDL: “good” cholesterol -removing cholesterol from TYPE IIA: FAMILIAL HYPERCHOLESTEROLEMIA the arteries and other tissues, HDL helps prevent Elevated LDL with normal VLDL due to block in LDL cholesterol from building up in the walls of blood degradation (LDL converted into VLDL in the liver) vessels. (anti-inflammatory & antioxidant) Even if the VLDL is normal there will be a possibility Normal body has higher LDL than HDL therefore of abnormal in LDL madaming kalaban si HDL na cholesterol but still Conversion of VLDL to LDL on the liver should be maintain balance. (but px eat fatty substance that’s normal but the problems are the degradation or why nagiging mas marami kalaban ni HDL resulting metabolism of the LDL → elevation of LDL to have a disease) RESULT: o ↑ serum cholesterol RISK FACTORS: o Normal TG levels o Smoking o o HTN CAUSE: o Obesity o Defects in synthesis/ processing of o DM LDL receptors CAUSES: CAUTION: o Lifestyle Factors o IHD is greatly accelerated ▪ Lack of exercise TREATMENT: ▪ Diet containing excess saturated o Diet fats o Cholestyramine o Inherited defect of lipoprotein metabolism o Niacin/ statins (defective metabolism) o Combination of both TYPE IIB: FAMILIAL COMBINED HYPERLIPIDEMIA o Obesity→ plaque→ DM, Arteries→ CHD Similar to type IIA except VLDL is also ↑ (Domino effect) RESULT: o ↑ serum TG and cholesterol levels TYPES OF MAJOR GENETIC HYPERLIPIDEMIA o Every time VLDL increased there will be an increase of LDL, of there’s an TYPE I: FAMILIAL HYPERCHYLOMICRONEMIA increase of LDL there will be an Massive fasting hyperchylomicronemia even increase of cholesterol → ↑TG and ↑ following normal dietary fat intake VLDL RESULT: CAUSE: o ↑ TG levels o Overproduction of VLDL by the liver ▪ TG – derived from glycerol and TREATMENT: 3 FA o Diet ▪ widespread in the adipose tissue o Drug therapy similar to type IIA ORIA, N. & AYENZA, S. 1  UNIT 4: HYPERLIPIDEMIA TYPE III: FAMILIAL DYSBETALIPOPROTEINEMIA Serum concentration of IDL is ↑ RESULT: o ↑TG and cholesterol levels CAUSE: o Overproduction/ underutilization of IDL due to mutant apolipoprotein E CAUTION: o Xanthomas and accelerated vascular disease ▪ Xanthomas – papules or nodules of the skin or mucous membranes that contain lipids (if present and the patient therapy are not fine and diet and patient have Type III there will be a higher acceleration) TREATMENT: o Diet o Niacin and Fenofibrate/statin TYPE IV: FAMILIAL HYPERTRIGLYCERIDEMIA VLDL ↑; LDL normal or decreased RESULT: o Normal to elevated cholesterol; ↑TG levels CAUSE: o Overproduction and/or ↓ removal of VLDL ad TG in serum CAUTION: o Relatively common o IHD o Obese o Diabetic o Hyperuricemic TREATMENT: o Diet o Niacin and/or Fenofibrate TYPE V: FAMILIAL MIXED HYPERTRIGLYCERIDEMIA PHARMACOLOGIC TREATMENT OF Serum VLDL and ↑ chylomicrons, LDL normal or ↓ HYPERLIPIDEMIA RESULT: o ↑ cholesterol and TG HMG CoA REDUCTASE INHIBITOR CAUSE: HMG CoA Reductase – enzyme needed for o ↑ production of VLDL/ removal of VLDL cholesterol synthesis and chylomicrons MOA: o Genetic defect (lipoprotein o Inhibit de novo cholesterol synthesis metabolism0 therefore depleting intracellular supply of CAUTION: cholesterol o Common in obese and diabetic o ↓ cholesterol: ↑ cell surface LDL receptor patients o ↓ cholesterol synthesis and LDL TREATMENT: catabolism o Diet o 1st line treatment for elevated risk of o Niacin and/or Fenofibrate or Statin ASCVD (Atherosclerotic cardiovascular Disease) AGENTS: o Lovastatin o Simvastatin o Pravastatin ORIA, N. & AYENZA, S. 2  UNIT 4: HYPERLIPIDEMIA o Atorvastatin ▪ PPAR activated which will cause ↓ TG o Fluvastatin concentration o Pitavastatin USES: o Rosuvastatin o Treatment of hypertriglyceridemia o Pitavastatin, Rosuvastatin & Atorvastatin o Treatment of Type III hyperlipidemia ▪ Most potent LDL-lowering statins followed AGENTS: by Simvastatin, Pravastatin, Lovastatin and o Gemfibrozil Fluvastatin o Fenofibrate ▪ First drug that will be given to the patient is ADR: simvastatin before given atorvastatin and o GI disturbances rosuvastatin (because they are the most o Gallstones because of increased potent statins) biliary cholesterol excretion ADR: o Myositis o ↑ liver enzyme o Myopathy + Rhabdomyolysis o May ↑ effect of warfarin ▪ Gemfibrozil + Statins o Rhabdomyolysis (rare muscle injury DRUG INTERACTION: where your muscles break down) o Increase effects of warfarin therefore it o Myopathy (heterogeneous group of will cause bleeding disorders primarily affecting the CONTRAINDICATIONS: skeletal muscle structure, metabolism, o Patients with severe hepatic or renal or channel function) insufficiency CONTRAINDICATIONS: o Patients with pre-existing gallbladder o Pregnancy and Lactation disease NIACIN BILE ACID SEQUESTERANT Most effective agent for ↑ HDL and ↓ LDL ↓ LDL MOA: MOA: o Inhibits lipolysis in adipose tissue o Anion exchange resins that bind therefore ↓ production of free FA (Fatty negatively charged bile acids and bile acid) salts in the SI ▪ Liver: normally use circulating o Resin/ bile complex is excreted in feces free FA as a major precursor of therefore ↓ in bile acid concentration TG synthesis (needed for o Hepatocytes: ↑ conversion of cholesterol other production of lipid) to bile acids (when bile acid arrive at the ↓ liver TG: ↓ VLDL: ↓LDL bile acid sequesterant they need to decreased level) USES: ▪ ↓ cholesterol: ↓LDL o Treatment of familial hyperlipidemia USES: o Severe hypercholesterolemia o Treatment of Type IIA and IIB (in ADR: combination with diet or niacin) o Intense cutaneous flush due to aspirin AGENTS: administration prior niacin o Cholestyramine ▪ Remedy: Slow titration or use ▪ Relieve pruritus caused by ▪ Before giving niacin to the accumulation of bile acids in patient, they give first aspirin patients with biliary stasis o Pruritus (itching) o Colesevelam o Inhibit tubular secretion of uric acid ▪ For patients with DM which can lead to gout ADR: CONTRAINDICATION: o May impair absorption of fat-soluble o Avoided in patients with hepatic vitamins (ADEK) disease o Interferes with absorption of drugs such as Digoxin, Warfarin and Thyroid hormones FIBRATES o May ↑ TG levels therefore it is ↓ TG levels, ↑HDL contraindicated in hypertriglyceridemia MOA: (>400mg/dL) o Member of the nuclear receptor family that regulates lipid metabolism CHOLESTEROL ABSORPTION INHIBITOR o PPAR – Peroxisome Proliferator Activated MOA: Receptor o Inhibits absorption of dietary and biliary o PPAR + Ligands (FA or eicosanoids)/ cholesterol therefore ↓ to the liver Antihyperlipidemic drug AGENTS: ORIA, N. & AYENZA, S. 3  UNIT 4: HYPERLIPIDEMIA o Ezetemibe ▪ Lowers LDL ▪ Adjunct to statin therapy or in statin intolerant patients PHARMACOKINETICS: o Metabolized in SI and liver via glucuronide conjugation CI: o Patients with severe hepatic insufficiency o Most of the drug in hyperlipidemia are CI with hepatic diseases OMEGA-3 FATTY ACIDS Omega 3 Polyunsaturated Fatty Acids (PUFAs) Essential FA: ↓ TG; inhibit VLDL and TG synthesis in the liver o EPA – Eicosapentanoic Acid o DHA – DocosahexanoicAcid ▪ Both of these can be found in tuna, halibut and salmon ▪ Fish oil capsules o Icosapent – Contains only EPA Adjunct to other lipid lowering agents ADR: o GI effects o Fishy after taste o Bleeding (those taking anticoagulant and antiplatelet) Reference(s): APA Format Handout & Discussion: GBAYENGRPhCIP©2024 MJASTUDILLORPh©2024 ORIA, N. & AYENZA, S. 4