FAFP2 Pharmaceutical care II Seminar: Hyperlipidemia and its management 29. 4. 2020 PharmDr. Bc. Dana Mazánková, Ph.D. mazankovad@vfu.cz Risk factors for obesity (according to their severity): Dyslipidemia Smoking Hypertension Psychosocial stress DM Increased ratio of waist compared to hip Lack of physical activity Inappropriate diet - cholesterol, triglycerides and phospholipids are trasported as lipoproteins • very low-density lipoproteins VLDLs • low-density lipoproteins LDLs • intermediate density lipoproteins IDLs • high-density lipoproteins HDLs • chylomicrons CM Undesired lipoproteins: VLDLs, LDLs → decrease the levels Desirable lipoproteins: HDLs → maintain levels Hyperlipidemia Parameter Optimal levels Total cholesterol ˂5.17 mmol/L Triglycerides ˂1.69 mmol/L LDL-cholesterol ˂2.58 mmol/L HDL-cholesterol Low >1.03 mmol/L High ≥1.55 mmol/L Management of hyperlipidemia: - primary outcome of therapy should be to lower LDL-cholesterol Ideal LDL:HDL ratio ˂ 3 (ratio 4 and more – risk of atherogenesis is high) Lipid profile Types of hyperlipidemia Elevated plasma lipoprotein Combined hyperlipidemia plasma triglycerides >2 mmol/L and LDL-cholesterol >3 mmol/L occurs as a result of metabolic disorders (e.g. insulin resistence) Isolated hypercholesterolemia LDL-cholesterol Isolated hypertriglyceridemia plasma triglycerides These three types can be combined with reduced, normal, or elevated HDL- cholesterol Familiar hypercholesterolemia - occurs due to a genetic risk - patients at risk of developing familiar hypercholesterolemia should be monitored, including children - this can lead to early onset of coronary heart disease, atherosklerosis Symptoms of hyperlipidemia - hyperlipidemia does not have any obvious symptoms - they are usually discovered during routine examination or until it reaches the danger stage of a stroke or heart attack Complication of hyperlipidemia - Atherosclerosis - accumulation of lipids, cholesterol and calcium - development of fibrous plaques within the walls of large and medium arteries - Coronary Artery Disease (CAD) - narrowing of the the arteries that supply blood to the myocardium - limiting blood flow - insufficient amounts of oxygen to meet the needs of the heart - Myocardial infarction (MI) - Ischemic stroke Conditions that cause secondary hyperlipidaemia - Diabetes mellitus - Hypothyroidism - Pregnancy - Alcohol abuse - Chronic renal failure - Hepatocelular disease - Systemic lupus erythematosus Drugs with adverse effect to the lipoprotein profile (drugs having obesity effect) - Amiodarone - Antipsychotics - Corticosteroids - Beta-blockers - Diuretics - Oral contraceptives - Tamoxifen - PAD - Thyreostatics Drugs having antiobesity effect - Antidepressants - bupropion - Antiepileptic drugs - topiramate - Psychotropics - aripiprazole - Antihypertensive - moxonidine - Insulin analogue - detemir (Levemir) Pharmaceutical Care in Hyperlipidaemia - treatment possibilities 1. Non-pharmacological recommendations 2. Pharmacotheraphy 3. Dietary supplements and functional foods for the treatment of dyslipidaemias 4. Participating in the screening of patients at risk 1. Non-pharmacological recommendations Lifestyle modifications to improve the plasma lipid profile  Quitting Smoking  Weight Reduction  Exercise  Moderate alcohol consumption  Diet: - mono-unsaturated fat - ω-3 fatty acids - min. 1 g EPA and DHEA daily - vit. D - 1000-5000 IU / day - restrict: - saturated fatty acids - carbohydrates with a high glycemic index STATINS Effects on lipids: • Decrease TG • Decrease LDL-cholesterol - by 25 – 45 % (depending on dose) • Increase HDL-cholesterol Combination theraphy: Bile acid binding resins (cholestyramine, colestipol) Nicotinic acid Triple combination Can also be combined with fibrates 2. Pharmacotheraphy Simvastatin - low price, first choice - metabolized by CYP-3A4 – high risk of drug interactions!!! Pravastatin, fluvastatin - unchanged CYP 3A4 (x simvastatin) - often in combination with fibrates Atorvastatin Rosuvastatin Pitavastatin Side effects od statins Liver - ALT elevation Muscle - rhabdomyolysis - dose related! - creatine kinase can increase 10 - 40x Diabetes mellitus - dysglycaemia and development of DM 2. type - benefit > risk even in patients with current DM or with risk factors for possible emergence of DM Kidney Diarrhea Headache Gallstones Statins – contraindications - liver disease - pregnancy, lactation Drugs potentially interacting with statins metabolized by CYP3A4 leading to increased risk of myopathy and rhabdomyolysis Anti-infective agents Calcium antagonists Other Itraconazole Verapamil Ciclosporin Ketoconazole Dilthiazem Danazol Posaconazole Amlodipine Amiodarone Erythromycin Ranolazine Clarithromycin Grapefruit juice Telithromycin Nefazodone HIV protease inhibitors Gemfibrozil FIBRATES Effects on lipids: • Decrease TG - by 30 – 50 % • Little effect on LDL-cholesterol !! • Increase HDL-cholesterol - by 10 – 15 % Gemfibrozil Bezafibrate The most commonly used: micronized fenofibrate dose of 267 mg EZETIMIBE Effects on lipids: • Decrease cholesterol • Decrease LDL-cholesterol - cholesterol absorption inhibitor - inhibits intestinal uptake of dietary and biliary cholesterol without affecting the absorption of fat-soluble nutrients - advantage: - it does not affect CYP 3A4 Combination with statins NICOTINIC ACID Effects on lipids: • Decrease TG - by 20 % • Decrease LDL-cholesterol - by 20 % • Increase HDL-cholesterol - by 20 % so-called „rule of 20 %“ • nicotinic acid derivatives Fixed dose combination: niacin + laropiprant - is recommended in combination with a statin 3. Dietary supplements and functional foods for the treatment of dyslipidaemias Fiber Insoluble fibre (cellulose, lignin, psyllium) Soluble fibre (glucomanan, galactomannan, inulin) preferable for weight loss Essential adequate intake of fiber + liquid! • Psyllium 10-15 g \ day • Pectin 20 to 30 g \ day • Glucomanan 3-4 g \ day Phytosterols - sitosterol, campesterol and stigmasterol - occur naturally in: - vegetable oils - in smaller amounts in: vegetables, fresh fruits, chestnuts, grains and legumes - added to: spreads and vegetable oils (functional margarine, butter and cooking oils), yoghurt and other foods - the daily consumption of 2 g of phytosterols can effectively lower TC and LDL-C by 7 – 10 % in humans Monacolin and red yeast rice - red yeast rice (RYR) is a source of fermented pigment that has been used in China as a food colorant and flavour enhancer - hypocholesterolaemic effects of RYR are related to monacolins with statin-like mechanism - inhibition of hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase Soy protein - soy protein has been indicated as being able to induce a modest LDLcholesterol lowering effect when replacing animal protein foods (this was not confirmed when changes in other dietary components were taken into account) Carnitine - involved in the transfer of fatty acids from the cytosol into the mitochondria where they are oxidized - recommended daily dose: 600 – 4 000 mg daily - carnitine is found naturally in: - meat and dairy products - other sources: nuts, cereals and asparagus, broccoli, garlic and other vegetables (the effect on weight loss has been not shown enough!) Dietary supplements and functional foods for the treatment of obesity Coffeine - regulation of thermogenesis - "thermogenic substances“: katechins - catechins probably inhibit the enzyme system catechol-Omethyltransferase, which reduces synaptic nerve endings in the adipocytes and the process of thermogenesis itself (real intensity and importance of this mechanism for reducing body weight been not discovered yet!) Garcinia Cambogia - hydroxycitric acid: - inhibit lipogenesis process - reduce the production of cholesterol and fatty acids - increases the production of glycogen in the liver - suppress appetite - increase production of body heat by activating the process of thermogenesis (real intensity and effect on weight loss insufficiently proven!) 4. Participating in the screening of patients at risk self-measurement of cholesterol levels – practical training device: Accutrend Triglycerides - for the key parameters used to detect cardiovascular disease: triglycerides - device is suitable for professional use as well as for self-testing