Post on 25-Dec-2015
Hyperlipidemia
Done by: Mohannad A. AL-Shibani Pharm.D intern
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Main pointsI. Pathophsiology
II. Management
III.Case
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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 drugs
Prevalence: 20.6 million children and adults – 12.0 % of the population -- have hyperlipedemia
Pathophsiology
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Diagnosed: 14.6 million people
Undiagnosed: 6.0 million people
In KSA 22% of population have an increase in cholesterol and /or triglyceride
A leading risk factor for CV disease
Pathophsiology
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Etiology:I. 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 HDL
II. Secondary 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 progestins
Pathophsiology
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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 susceptibility
Pathophsiology
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Risk factor:Modifiable
HTN(> 140/90 mmHg )DMObesity InactivityLow HDL(<40 mg/dl)SmokingChronic kidney disease
Pathophsiology
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higher Cholesterol Levels Associated With CHD Risk higher
0
25
50
75
100
125
150
204 205-234 235-264 265-294 295
CH
D I
NC
IDEN
CE P
ER
1000
SERUM CHOLESTEROL (MG/100 ML)
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Complication:1) Fatty streaks: its reversible process while
atherosclerosis (plaque) irreversible
2) Corneal xanthelasma: accumulation of yellow plaque underneath skin ,eyelid(irreversible)
3) Planar exanthema: appear on hand,Knee,&elbow (irreversible)
4) Irruptive exanthema : rashes due increase TG (reversible)
Pathophsiology
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Characteristic of plasma lipoprotein:
Pathophsiology
APPEREANCE AFTER REREG.
% PROTIEN CONTENT
% of TGL Major lipid Lipoprotein class
Cream layer 1-2 3-7 TGL(Diet) chylomicron
turbid 6-10 20-30 TGL(Endogenous)
VLDL
clear 18-22 51-58 cholesterol LDL
clear 45-55 18-25 cholesterol HDL
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Classification: 1-phenotypic (Fredrickson
classification)
Pathophsiology
TGL LDL Lipoprotein in excess
familial class
+++ + chylomicron hyperchylomicronemia
I(rare)
N.L. ++++ LDL hypercholesrolemia
IIa
++ +++ LDL&VLDL Combined hyperlipedemia
IIb
+++ ++ IDL dysbetalipoprotenimia
III(rare)
++++ + VLDL hypertriglyceridemia
IV
++++ ++ VLDL&CHYLOMICRON
Combined hypertriglyceridemia
V(rare)13
Classification: 2-(Genetic classification)
Pathophsiology
Homozygous familial hypercholesterolemia
Heterozygous familial hypercholesterolemia
Two defect gene One defect gene
Atherosclerosis 1 st/2nd decade (10-20 years)
Atherosclerosis 4 th decade (40-50 years)
Total cholesterol =18-25 mmol/l Total cholesterol =7.7-12.9 mmol/l
AMI before age 20(if not treated)
1 case per 1 million persons The prevalence of is approximately 1 case per 500 persons in U.S
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Diagnosis: measure Serum lipid profile after 12 hr. fasting like
I. total cholesterolII. TGIII. HDL-cholesterolIV. calculated LDL-cholesterol and VLDL)
VLDL= ( TGL / 5 )LDL= {Total cholesterol – (HDL +VLDL)}
Pathophsiology
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Normal level of lipoprotein: National Cholesterol Education Program Adult Treatment Panel III
Screening: A fasting lipid profile should be repeated every 5 yr. Lipid measurement should be accompanied by assessment of other cardiovascular risk factors
Pathophsiology
mmol/L mg/dL lipoprotein
<5.17 <200 Total cholesterol
>1.03 >40 HDL
<1.7 <150 Triglyceride
<3.33 <130 LDL
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II-Managment
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I. Life style modification
II. Drug therapy like:
Bile acid sequestrants Nicotinic acid derivative Fibric acid derivative HMG-CoA reductase inhibitor Cholesterol absorption inhibitors
managment
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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 start
managment
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PHARMACOTHERAPEUTIC OPTIONS
cholesterol-lowering medications may be considered in addition to lifestyle changes.
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Drug therapy:1) Bile acid sequestrantso M.O.A:block intestinal bile acid reabsorption,
forcing up-regulation of hepatic LDL receptors to recruit circulating cholesterol for bile synthesis
managment
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o usually used with statins or with nicotinic acid to augment LDL-cholesterol reduction
o their use is limited by adverse effects of bloating, nausea, cramping, and constipation. They may also increase TGL so use only in type 2A
o Example: cholestyramine ,and colestipol
managment
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Cholestyramine available in powder form so can mix with orange drink or juice to minimize gritty texture
Dose: 4 g QID Colestipol have better adherence b/z its
odorless and tasteless, available in tablet form
Dose: 2 to 16 grams/day once or in divided doses
managment
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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 plasma
the most effective drug for increasing HDL
Principle use in type 2B as first line and second line in type 2A,may used as first line or alternative in type4&5
managment
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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/d
managment
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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 alone
managment
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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 stiffness
managment
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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 mortality
managment
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Drug of choice in type 2A & 2B b/z it mainly act on LDL
S.E: 1)Mylagia 2)increase liver function test
Example: 1-atorvastatin(lipitor) 2-simvastatin(zocor)
3-pravastatin(lipostat) 4-fluvastatin(lescol)
5-rosuvastatin(crestor)
managment
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Comparative efficiency and pharmacology of the statins.
DrugReduction in LDL-C
)%(
Increase in HDL-
C)%(
Reduction in TG)%(
Reduction in TC
)%(Metabolism T1/2 (h)
Atorvastatin 26-60 3-15 11-53 25-45 CYP3A4 13-30
Simvastatin 26-47 8-16 \12-34 19-36 CYP3A4 1-3
Fluvastatin 22-36 3-11 12-25 16-27 CYP2C9 3-5
Rosuvastatin 45-63 8-14 10-35 33-46 CYP2C9 19
Pravastatin 22-34 2-12 15-24 15-26 Sulfation 2-3
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managment
Cost in SR LDL lowering & NAME of drug
125 39% ATORVASTATIN 10mg
201 43% 20 mg
229 50% 40mg
60% 80mg
22% Fluvastatin 20mg
24% 40 mg
119 30% 80 mg
68 22% Pravastatin 10 mg
111 32% 20 mg
34% 40 mg
45% Rosuvastatin 5 mg
116 52% 10 mg
197 55% 20 mg
%63 40 mg
48 30% Simvastatin 10 mg
54 38% 20 mg
65 41% 40 mg
47% 80 mg
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managment
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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 elevation
managment
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Doesn’t influence the activity of CYP-450
S.E.: abdomain pain ,fatigue , diarrhea
Example: Ezetemibe (Ezetrol) cost:225 SR
Dose: 10 mg OD approved in Oct.2002
managment
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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 SR
managment
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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 ezetemibe
managment
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3-In 6 weeks, evaluate if LDL goal is achieved. If not, intensify drug therapy. If LDL goal is achieved, treat other lipid risk factors
4-Every 4 - 6 months, monitor response and adherence to therapy
IF TGL high alone used first niacin or fibrate
IF HDL low alone consider first niacin
managment
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LDL is the primary target of lower cholesterol & better predictor of CHD
NCEP recommend full lipid panel every 5 years
Dietry therapy should consider first line in tratment
Drug therapy should combined with Life style modification
Selection of drug is based on efficiacy ,side effect &cost
Take Home points:
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III-case study
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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 dyspnea
Vital signs:
Wt : 82 Kg HR: 20 mm/hr Temp: 37.2 c
BP: 119/77 mm Hg
CC: generalized fatigue from any activity , difficult in breathing and increase in its heart rate with sweating
Physical examination:
HEENT: normal Chest: clear
CVS: S1 + S2+O Abd: normal and soft Extremities: normal
Case studyFile no.:552020
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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 BID
She took ASA 81 mg OD Patient note non compliance to drug due financial
reason .and not adherence to her diet
Case study
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Family history: Her mother with DM type II
Social 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 study
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Case studyHbA1c%
2 hrmmol/l
FBSmmol/l
TGLmmol/l
HDLmmol/l
LDLmmol/l
date
11.8 8.6 1.87 3.4 9/3/06
11.1 7.5 3.6 4/3/07
7.2 10.5 5.9 3.2 13/6/07
7.2 10.7 6.8 1.43 3.6 28/10/07
7.3 11.4 6.1 1.34 3.91 2/2/08
7.5 10.7 6.8 2.2 1.40 3.5 5/5/08
7.7 11.4 6.2 1.56 1.37 3.71 11/10/08
7.5 11.4 6.10 1.91 1.32 4.03 16/12/0845
Plan:
The most common cause of therapy failure is:1) the wrong medication, 2) the wrong
dose,
3) patient non-compliance
On 5/5/2008………………….
Case study
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atorvastatin 10 mg equivalent to 20 mg simvastatin
In case of DM : 1)advice to increase dose of glibenclamide to
5mg TID
In case of hyperlipidemia: 1)Advice to increase dose of simvastatin to 20
mg OD
Case study
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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 market
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Total cost per month in SR
Alternative with same active constituent
Total cost per month in SR
medication
20 (Glibil) 50 Glibenclamide(Daonil) 5mg
BID
9 (Metfor) 21 Metformin(Glucophage)
500mg BID
75 ((Statin 125 Atorvastatin(lipitor )10 mg
OD
54 ((Simva 119 Or Simvastatin(zocor)20 mg
OD
4 same 4 Aspirin))ASA 81 mgOD
Total cost=108 SROR 87 SR
TOTAL cost=200 SROR 194 SR
,
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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: 227-239
Stone NJ, Blum CB, Winslow E. Management of lipids in clinical practice. 5th ed. Caddo, OK, Professional Communications, Inc., 2005.
Refrences
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