Hyperlipidemia Done by: Mohannad A. AL-Shibani - PowerPoint Presentation

1. HyperlipidemiaDone by: Mohannad A. AL-Shibani Pharm.D intern1

2. Main points PathophsiologyManagementCase2

3. Definition: an increase plasma level of cholesterol and / or triglyceride Hyperlipidemia may be secondary to disorder like DM , hypothyroidism, nephrotic syndrome , obesity, high alcohol intake and some drugsPrevalence: 20.6 million children and adults – 12.0 % of the population -- have hyperlipedemia Pathophsiology3

4. Diagnosed: 14.6 million peopleUndiagnosed: 6.0 million people In KSA 22% of population have an increase in cholesterol and /or triglycerideA leading risk factor for CV diseasePathophsiology4

5. Etiology:Primary causes(genetic): single or multiple gene mutations that result in either overproduction or defective clearance of TG and LDL cholesterol, or in underproduction or excessive clearance of HDLSecondary causes(lifestyle &others): xss. dietary intake of saturated fat, cholesterol, and trans fats. Like polyunsaturated or monounsaturated fatty acids , diabetes mellitus, alcohol over use,CKD, hypothyroidism, biliary cirrhosis and drugs, such as thiazides, β-blockers , estrogen and progestinsPathophsiology5

6. Risk factor:Non – modifiable:Age >45 for male , >55 for femaleMale sex (at risk 4-5 times more than female)Family history of premature CHD (1st-degree relative) Genetic susceptibilityPathophsiology6

7. Risk factor:ModifiableHTN(> 140/90 mmHg )DMObesityInactivityLow HDL(<40 mg/dl)SmokingChronic kidney diseasePathophsiology7

8. higher Cholesterol Levels Associated With CHD Risk higher0255075100125150 204205-234235-264265-294 295CHD Incidence per 1000Serum Cholesterol (mg/100 mL)8

9. Complication:Fatty streaks: its reversible process while atherosclerosis (plaque) irreversibleCorneal xanthelasma: accumulation of yellow plaque underneath skin ,eyelid(irreversible)Planar exanthema: appear on hand,Knee,&elbow (irreversible)Irruptive exanthema : rashes due increase TG (reversible)Pathophsiology9

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11. Characteristic of plasma lipoprotein:PathophsiologyAPPEREANCE AFTER REREG.% PROTIEN CONTENT% of TGLMajor lipidLipoprotein classCream layer1-23-7TGL(Diet)chylomicronturbid6-1020-30TGL(Endogenous)VLDLclear18-2251-58cholesterolLDLclear45-5518-25cholesterolHDL11

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13. Classification: 1-phenotypic (Fredrickson classification)PathophsiologyTGLLDLLipoprotein in excessfamilialclass++++chylomicronhyperchylomicronemiaI(rare)N.L.++++LDLhypercholesrolemiaIIa+++++LDL&VLDLCombined hyperlipedemiaIIb+++++IDLdysbetalipoprotenimiaIII(rare)+++++VLDLhypertriglyceridemiaIV++++++VLDL&CHYLOMICRONCombined hypertriglyceridemiaV(rare)13

14. Classification: 2-(Genetic classification)PathophsiologyHomozygous familial hypercholesterolemiaHeterozygous familial hypercholesterolemiaTwo defect geneOne defect geneAtherosclerosis 1 st/2nd decade (10-20 years)Atherosclerosis 4 th decade (40-50 years)Total cholesterol =18-25 mmol/lTotal cholesterol =7.7-12.9 mmol/lAMI before age 20(if not treated)1 case per 1 million personsThe prevalence of is approximately 1 case per 500 persons in U.S14

15. Diagnosis: measure Serum lipid profile after 12 hr. fasting liketotal cholesterolTGHDL-cholesterolcalculated LDL-cholesterol and VLDL)VLDL= ( TGL / 5 )LDL= {Total cholesterol – (HDL +VLDL)}Pathophsiology15

16. Normal level of lipoprotein: National Cholesterol Education Program Adult Treatment Panel IIIScreening: A fasting lipid profile should be repeated every 5 yr. Lipid measurement should be accompanied by assessment of other cardiovascular risk factorsPathophsiologymmol/Lmg/dLlipoprotein<5.17<200Total cholesterol>1.03>40HDL<1.7<150Triglyceride<3.33<130LDL16

17. II-Managment17

18. Life style modificationDrug therapy like:Bile acid sequestrantsNicotinic acid derivativeFibric acid derivativeHMG-CoA reductase inhibitorCholesterol absorption inhibitorsmanagment18

19. Life style modification:decreasing intake of saturated fats and cholesterol; increasing fiber, complex carbohydrates; stop smoking and maintaining IBW. Referral to a dietitian is often useful, Drugs are the next step when lifestyle changes are not effective after 3-4 month. However, for patients with extremely elevated LDL-cholesterol (> 200 mg/dL [> 5.2 mmol/L]) and those at high cardiovascular risk, drug should accompany with diet and exercise from the startmanagment19

20. PHARMACOTHERAPEUTIC OPTIONScholesterol-lowering medications may be considered in addition to lifestyle changes.20

21. Drug therapy:1) Bile acid sequestrantsM.O.A:block intestinal bile acid reabsorption, forcing up-regulation of hepatic LDL receptors to recruit circulating cholesterol for bile synthesismanagment21

22. usually used with statins or with nicotinic acid to augment LDL-cholesterol reductiontheir use is limited by adverse effects of bloating, nausea, cramping, and constipation. They may also increase TGL so use only in type 2AExample: cholestyramine ,and colestipolmanagment22

23. Cholestyramine available in powder form so can mix with orange drink or juice to minimize gritty textureDose: 4 g QID Colestipol have better adherence b/z its odorless and tasteless, available in tablet formDose: 2 to 16 grams/day once or in divided dosesmanagment23

24. 2-Nicotinic acid derivative:M.O.A.: alters lipid profiles has not been well defined. It may inhibition of release of free fatty acids from adipose tissue, and increased lipoprotein lipase activity, which may increase the rate of chylomicron triglyceride removal from plasmathe most effective drug for increasing HDLPrinciple use in type 2B as first line and second line in type 2A,may used as first line or alternative in type4&5managment24

25. S.E.: hyperglycemia , hyperurecemia ,itching and cutaneous flushing may restrict its use but….Dose: 500mg at within meal or after to reduce the incidence and side effects which may occur and titrated dose to 2000 mg/dmanagment25

26. 3-fibric acid derivative:M.O.A.:increases lipolysis and elimination of triglyceride-rich particles from plasma by activating lipoprotein lipase and reducing production of apoprotein C-III (an inhibitor of lipoprotein lipase activity).Drug of choice in type 4 and may used in 2B and in decrease HDL alonemanagment26

27. Example: 1)gemfibrozil(lopid) dose:600 mg BID Cost: 55 SR, 2)fenofibrate(lipanthyl) dose:200 mg OD Cost: 49 SR Other: 3) clofibrate(use restricted due high mortality) 4) benzofibrate(use restricted due stone formation)S.E: muscle cramps and stiffnessmanagment27

28. 4-HMG-CoA reductase inhibitor:M.O.A: inhibit hydroxymethylglutaryl CoA reductase, a key enzyme in cholesterol synthesis, leading to up-regulation of LDL receptors and increased LDL clearance. They reduce LDL-cholesterol by up to 60%Not only have statins improved lipid profiles, but they have in turn reduced cardiovascular morbidity and mortalitymanagment28

29. Drug of choice in type 2A & 2B b/z it mainly act on LDLS.E: 1)Mylagia 2)increase liver function testExample: 1-atorvastatin(lipitor) 2-simvastatin(zocor) 3-pravastatin(lipostat) 4-fluvastatin(lescol) 5-rosuvastatin(crestor) managment29

30. Comparative efficiency and pharmacology of the statins.DrugReduction in LDL-C (%)Increase in HDL-C (%)Reduction in TG (%)Reduction in TC (%)MetabolismT1/2 (h)Atorvastatin26-603-1511-5325-45CYP3A413-30Simvastatin26-478-16\12-3419-36CYP3A41-3Fluvastatin22-363-1112-2516-27CYP2C93-5Rosuvastatin45-638-1410-3533-46CYP2C919Pravastatin22-342-1215-2415-26Sulfation2-330

31. managmentCost in SRLDL lowering &NAME of drug12539%ATORVASTATIN 10mg20143% 20 mg22950% 40mg60% 80mg22%Fluvastatin 20mg24% 40 mg11930% 80 mg6822%Pravastatin 10 mg11132% 20 mg34% 40 mg45%Rosuvastatin 5 mg11652% 10 mg19755% 20 mg%63 40 mg4830%Simvastatin 10 mg5438% 20 mg6541% 40 mg47% 80 mg31

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34. 5-cholesterol absorption inhibitor:M.O.A: inhibit intestinal absorption of biliary and dietry cholesterol Decrease LDL by 15-20% Increase HDL by 2.5-5%Decrease TGL by 0-2%can be used as monotherapy in patients intolerant to statins or added to statins for patients on maximum doses with persistent LDL-cholesterol elevationmanagment34

35. Doesn’t influence the activity of CYP-450S.E.: abdomain pain ,fatigue , diarrheaExample: Ezetemibe (Ezetrol) cost:225 SRDose: 10 mg OD approved in Oct.2002managment35

36. New combination of ezetemibe and simvastatin in saudi market called (INGEY) or (Vytorin)Dose : - 10/20 mg cost: 273 SR -10/40 mg cost:296 SRmanagment36

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38. Guidelines for treatment according NCEP:1- Initiate LDL-lowering drug therapy with a statin, or bile acid sequestrant, or nicotinic acid.2- In 6 weeks, evaluate if LDL goal is achieved. If not,Consider higher dose of statin or add bile acid sequestrant or nicotinic acid or ezetemibemanagment38

39. 3-In 6 weeks, evaluate if LDL goal is achieved. If not, intensify drug therapy. If LDL goal is achieved, treat other lipid risk factors4-Every 4 - 6 months, monitor response and adherence to therapyIF TGL high alone used first niacin or fibrateIF HDL low alone consider first niacinmanagment39

40. LDL is the primary target of lower cholesterol & better predictor of CHDNCEP recommend full lipid panel every 5 yearsDietry therapy should consider first line in tratmentDrug therapy should combined with Life style modification Selection of drug is based on efficiacy ,side effect &costTake Home points:40

41. III-case study41

42. HPI:68 years Yemenian female, 82 kg, with known case of type 2DM, and dyslipidemia . She came to family clinic complaining of fatigue ,palpitation and dyspneaVital signs: Wt : 82 Kg HR: 20 mm/hr Temp: 37.2 c BP: 119/77 mm HgCC: generalized fatigue from any activity , difficult in breathing and increase in its heart rate with sweatingPhysical examination: HEENT: normal Chest: clear CVS: S1 + S2+O Abd: normal and soft Extremities: normal Case studyFile no.:55202042

43. Past medical history:1) Hyperlipidemia from 2 years treated by: Atorvastatin (lipitor) 10 mg OD then changed ……2)Type 2 DM from 4 years treated by: metformin (glucophage) 500 mg BID glibenclamide(daonil) 5 mg BIDShe took ASA 81 mg ODPatient note non compliance to drug due financial reason .and not adherence to her dietCase study43

44. Family history: Her mother with DM type IISocial history: married, non smoker , poor education and financial proplem Lab result: 1-Glycated haemoglobin level is 7.5% 2- LDL=4.03mmol/l (<3.3mmol/l) 3- HDL=1.32 mmol/l (>1.03mmol/l) 4-TGL=1.91 mmol/l (<3.3mmol/l) 5- chol=5.5mmol/l (<5.17mmol/l) 6- FBS= 6.1mmol/l (<7 mmol/l) 7- 2hr= 11.4mmol/l (<11.0 mmol/l) Case study44

45. Case studyHbA1c%2 hrmmol/lFBSmmol/lTGLmmol/lHDLmmol/lLDLmmol/ldate11.88.61.873.49/3/0611.17.53.64/3/077.210.55.93.213/6/077.210.76.81.433.628/10/077.311.46.11.343.912/2/087.510.76.82.21.403.55/5/087.711.46.21.561.373.7111/10/087.511.46.101.911.324.0316/12/0845

46. Plan:The most common cause of therapy failure is:1) the wrong medication, 2) the wrong dose, 3) patient non-complianceOn 5/5/2008………………….Case study46

47. atorvastatin 10 mg equivalent to 20 mg simvastatinIn case of DM : 1)advice to increase dose of glibenclamide to 5mg TIDIn case of hyperlipidemia: 1)Advice to increase dose of simvastatin to 20 mg ODCase study47

48. Recommendation:Educate the patient about his medication uses and administrationAdvise patient to take the medication regularly to avoid the complication in futureIllustrate to the patient importance of diet Try to help the socioeconomic proplem of the patient by shown him the cheapiest alternative of his medication availble in market48

49. Total cost per month in SRAlternative with same active constituentTotal cost per month in SRmedication20(Glibil)50Glibenclamide(Daonil )5mg BID9(Metfor)21Metformin(Glucophage)500mg BID75((Statin125Atorvastatin(lipitor) 10 mg OD54((Simva119Or Simvastatin(zocor)20 mg OD4same4Aspirin))ASA 81 mgODTotal cost=108 SROR 87 SR TOTAL cost=200 SROR 194 SR,49

50. Marry A. Kimble.Handbook of Applied Therapuetics.Lippincott Williams and Wilkins, MD.8th Ed, 2007; Chapter 12, page:127-143 Grundy SM, et al. Implications of Recent Clinical Trials for the National Cholesterol Education Program Adult Treatment Panel III Guidelines. Circulation 2004; 110: 227-239Stone NJ, Blum CB, Winslow E. Management of lipids in clinical practice. 5th ed. Caddo, OK, Professional Communications, Inc., 2005.Refrences50

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