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As regards TG
a.
b.
c.
d.
2
Putative factors:
A. Homocyteine
B. Lpa
C. Small LDL
D. C-reactive protein,
E. Chronic infection
NB. Some criteria that raise the suspicion of familial dyslipidemia are:
1. CHD or dyslipidemia in first degree female < 65y
2. CHD or dyslipidemia in first degree males < 55Y
3. Xanthelasma OR corneal arcus under age of 50
4. Tendon xanthomata
5. High TC at any age
TG
TC
LDL.C
I
IIa 1/500
IIb 1/200
III
1/5000
+++
N
++
+++
+
++
++
+
IV
++
V
+++
1/1000000
Polygenic +
HC
N
++
++
N
Raised
lipoproteins
Chylomicrons
LDL
LDL/VLDL
VLDL/chylo
Atheroma
risk
N
+++
+++
++
N/+
VLDL
++
VLDL/Chylo
++
++
LDL
++
Associated
Signs
Xanthomas,CA
Common
Obesity,
DM,HT
xanthomas
Obesity, DM,
Hyperuricemia,
alcoholic
Obesity, DM
Family H 25%
No physical
3
a. Antihypertensives (Diuretics (thiazides (LDL-c, VLDL-c, TG& Loop, B. blockers
TG, HDL). What are the alternatives?
b. Oral contraceptives (Ht, DM)
c. Androgens
d. Corticosteroids (TC, LDL, TG, VLDL)
e. Ciclosporines (LDL, Ht, DM) + corticosteroids.
f. Progestogens (LDL, HDL)
g. Vit. A derivatives
h. Protease inhibitors, Tamoxifen
i. Hepatic microsomal enzyme inducers (like phenytoin, rifampicin, carbamazepine,
grisofulvin etc). Increase all (HDL, LDL, VLDL) But good ratio TC: HDL
LDL goal
Mg/dl
<160
Diet/life style
indicated
160-190
Drug therapy
indicated
>190
<130
130-160
>160
<100
<100
<70
100-130
100-130
70-100
>130
>130
>100
Step I
30%
10%>
Up to 10%
Up to 15%
55%<
15%
mg/day 300
Step II
30%
7% >
Up to 10%
Up to 20%
55%<
15%
mg/day 200
3. Continue on diet and life style changes for 3-6M if ineffective or unacceptable or if
there is evidence of IHD, hypertension, DM, positive family history, or there is
hypertriglyceridemia, lipid lowering drugs should be used.
5
6. Control of diabetes
7. Low dose aspirin: in high risk especially with HT
8. Lowering of cholesterol by statins according to the risk factors (<200 TC, <130
LDL)
(According to Sheffield table (Age, gender, smoking, DM, BP, TC/HDL.c
1. If the CHD risk < 15% life style modification and reassess after 5 years
2. If the CHD risk > 15% but TC < 200 mg/dl Life style modification + Yearly lipid
profile + Treat risk factors
3. If the CHD risk > 15% and Tc> 200 mg/dlLife style modification + Drug therapy
e.g. statin.
B) Secondary prevention:
9. Statins except when the major abnormality is low HDL
10. Treat other risk factors
11. Low dose aspirin
12. ACE inhibitors for left ventricular dysfunction
13. B. blockers for MI
14. Warfarin or aspirin for those over 60 y who have atrial fibrillation
15. Omega 3 fatty acids
Treatment of hypertriglyceridemia:
1. Begin with non-pharmacological measures
2. Control of diet, weight diabetes, alcohol
3. If insufficient, use drugs as follows:
a. Modest TG + TCuse statins
b. Extremely high TGuse fibrates or niacin
c. High risk individuals combine statins + fibrates
The use of drugs in lowering plasma lipid concentration:
a.
b.
c.
d.
e.
f.
g.
h.
i.
j.
k.
l.
Drug combinations:
4. If one drug is not effective, you can add one or more drug, the following drug
combinations are possible:
a. Fibrates + Resins ( familial combined hyperlipidemia)
b.
c.
d.
e.
Statins
Simva, fluva,
Atorva-statin
(10-80 mg)
Resins
Colistipol
Choestyramine
(15-30 gm)
Fibrates
Nicotinic acid
Bezafibrate
1.5-6gm/day
400-600 mg/day
Gemfibrozil
600mg/12h
Lower TG, VLDL/2ry C,LDL
Lipoprotein lipase E
Adipose tissue lipolysis
TC
TG
VLDL
LDL
HDL
Side effects
Hepatitis
Hepatic injury
Hepatic injury
Myositis
Muscle injury
Muscle injury
GIT
GIT
GIT(constipatio
n)
Uses
Other uses
Others
Pregnancy and
lactation
Drug-drug
interactions
Hypersensitivity
NO
C.P450 inducers and
inhibitors (grapefruit)
Nicotinic, cyclosporine
Yes
Binding
drugs( digoxin,
diuretics,thyroxi
ne, statins, Vit K
Large doses
SR
Glucose
Uric acid
GIT(PU)
NO
Statins& Oral
anticoagulants & oral
antidiabetics& Resins&
Ciclosporin
7
Q15. For how long will you advise for diet and life style changes? 1ry& 2ry
Q16. What are the general lines for primary prevention for cases of dyslipidemia?
Q17. What are the general lines for secondary prevention for cases of dyslipidemia?
Q18. What is the mechanism of action of statins?
Q19. Why statins are useful in CHD?
Q20. What are the most important side effects of statins?
Q21. What is the effect of grapefruit on statins effect and toxicity?
Q22. What is the mechanism of action of fibrates?
Q23. What are the main side effects of fibrates?
Q24. What are the drug-drug interactions of statins?
Q25. What are the drug-drug interactions of fibrates?
Q26. What is the mechanism of action of Resins?
Q27. Which drug raises the TG?
Q28. What are the precautions taken while taking resins?
Q29. What are the major adverse effects of Resins?
Q30. What is the mechanism of action of nicotinic cid?
Q31. What are the major side effects of NA?
Q32. What is your opinion about fish oil in treating hyperlipidemia?
Q33. Why statins are preferred to be taken at evening?
Q34. When do you expect the results of statins?
Q35. How can you overcome the hot flushes of nicotinic acid?
Q36. Are the accompanying statements false or true? Why?
a. An individual with high HDL there is a lowering in the risk of CHD if the HDL is reduced.
b. An important contributor to the development of hypercholesrolemia is a genetic defect.
c. Anion exchange resins act by enhancing the absorption of bile acids from the gut.
d. Decreased cholesterol synthesis results in increased number of HDL receptors
e. Simvastatin lowers LDL by 5%
f. Co-administration of bile acid resins and statins has no greater effect than giving each drug
separately.
Case discussion
Case 1: A 42-year-old woman, has a plasma total triglyceride of 1042 mg/dl and total cholesterol
of 368 mg/dl. Plasma HDL is 72 mg/dl. Electrophoresis of the plasma lipoproteins an intense pre-Bband; all others are normal or absent. Blood glucose is normal. She is not taking any medications.
Q1. What hyperprlipoproteinemia does this patient most likely have?
Q2. What is the greatest health risk to this patient based upon the provided information?
Q3. Which individual drug or combination can safely be used to produce maximum lowering
of her plasma lipids?
Q4. IF the patient is given fenofirate to treat his condition, what enzyme or receptor activity
will most increase?
Case 2; Awatif a 45 years is an asymptomatic female. She is screened with a lipoprotein profile
during an annual physical evaluation. She has non-insulin dependent DM treated with 60 U NPH.
She is overweight. Her fasting lipoprotein profiles: total cholesterol 234 mg/dl, triglycerides 2300
mg/dl, HDL-24 mg/dl, LDL 160 mg/dl, fasting BG 290 mg/dl. What is your assessment of CHD
risk and what treatment if any should be given?
Control DM-Fibrates-Lipid profile<400 mg/dl then LDL if >100 give statin.
Case 3;
Mr D.F is a 43-year-old man who has been relatively fit and well for the past 20 y
during which he has rarely visited his GP. Two weeks ago he was admitted to hospital suffered MI.
On questioning it was revealed that his brother had died in a road traffic accident at the age of 19
and his father had died from CHD aged 54Y. Examination of Mr D.F. revealed tendon xanthomas.
Blood drawn within 2 h of the onset of MI revealed TC 350, HDL 40 and triglycerides 200 mg/dl
Questions
Q1. Calculate the concentration of LDL and comment on the finding?
Q2. What is the likely diagnosis and treatment of DF on discharge?
Q3. D F wants to know why he was not identified as being at high risk of CHD before he
suffered his MI?
Case 4; Mr P.T. is a 50-year-old man with a blood pressure of 140/85 mm Hg and type 2 DM,
but no history of CHD. He smokes 10 cigarettes a day. On a routine clinic visit he is found to have a
TC of 240 mg/dl, HDL 30 , and TG 150 mg/ dl.
Questions:
Q1. Is PT at high risk of CHD?
Q2. What advice/ treatment would be appropriate?
Case 5: Mrs Soad is a 49-year-old woman who visits her doctor complaining of menopausal
symptoms including hot flushes, night sweats and irritability. She is concerned about her risk of
CHD because her husband and mother have angina. Her mother developed angina at the age of 68
and 5 years later was diagnosed with breast cancer. In general Mrs Soad does not like taking
medicines and would not much prefer exercise to hormone replacement therapy (HRT)?
Q1. Is Mrs Soad at risk of CHD?
Q2. What advice would you give her about the relative benefits of exercise and HRT?
Case 6. A 58-year-old man has recovered from anterior MI. His fasting plasma cholesterol is 210
mg/dl. You want to reduce his risk of a further MI by lowering his cholesterol.
a. What advice would you give him?
9
b. What drug would you recommend and why?
c. What reduction of plasma cholesterol would you expect, and when would you expect an
adequate response?
d. How do statins work?
e. What target total cholesterol would you aim for?
f. What unwanted effects would you warn him about?
g. If the target cholesterol is not attained, how could you reduce cholesterol further?
h. How the additional drugs you have recommended work?
Case 7:
A 45-year- man has a plasma total triglyceride of 105 mg/dl and total cholesterol of 431 mg/dl.
Plasma HDL is 53 mg/dl. Electrophoresis of his plasma lipoproteins show an intense B-band; all
others are normal. He is taking itraconazole for persistent fungal infections. He had two older
brothers who both died of MI at 53 and 51 years of age.
Q1. What hyperlipoproteinemia does this patient most likely have?
Q2. What is the most likely biochemical basis of this patient's hyperlipidemia?
Q3. What drugs would be contraindicated in this patient if his use of itraconazole was not
discontinued?
Q4. If the patient was treated with cervistatin, what adverse effects would be of greatest
potential concern?
Case 8;
Essam, a 53-year-old man, has a mean LDL.c of 200 mg/dl determined on two
appointments after following a step II diet, low-saturated fat diet for 6 months. His high BP is under
marginal control with enalapril 10 mg/day ( BP,134/88). His glucose level is 80 mg/dl. He reports
no family history of premature CHD events. He does not smoke. His HDL.c is 45 mg/dl. There are
no secondary or familial causes of his hypercholesterolemia, and no evidence of atherosclerosis
was found during his initial medical evaluation. He jogs 2 miles 3 times a week. Is Essam a
candidate of cholesterol lowering drug therapy, and if so,
Q 1; What drug (s) should be considered for lowering his LDL.c level?
Q2. According to the answer in previous question either a bile acid resin, niacin, or HMG-CoA
reductase inhibitor would be acceptable? What about fibrates?
Q3. Which one of these 3 major drugs would be used first to manage L.W lipid disorder? Your
goal? Which drug from this group? Why? If failed, what will you do? Combinations?
Q4. How can you monitor each of these drugs?
A. BAR (Lipid profile /4-8 w)
B. Statins (Lipid profile, LFTs (0-3m-A), CPK((0-symptoms)
C. Niacin therapy (Lipid profile, LFTS (0-6-8w for 1year, symptoms) Glucose, uric
acid, BP (hypertensive & elderly patients)
Q5. What are the doses of theses drugs? Time of administration?
Q6. What is the difference between colesevelam and cholestyramine?
Q7. What do you know about Ezetimibe?
Q8. What role can supplemental fibers play in the treatment of the patient? 5%
Q9. Can fish oils be used to treat elevated LDL-C in patient's treatment?TG 30-60%
Case 9. Asmaa is a 55-year-old recently postmenopausal woman. She has a mean LDL of 200
mg/dl after a 6-month trial of a step II diet. She has a strong family history of CHD. Her mother is
10
78 years complaining of fracture as a result of osteoporosis. No DM, No HT. She smokes 10
cigrettes/day. HDL 58 mg/dl. Tg 78 mg/dl. No evidence of secondary or familial dyslipidemia and
no evidence of atherosclerosis. No hysterectomy. Physically active and with normal weight. She
complains of hot flashes and night sweats.
Q1. Does this patient need cholesterol lipid lowering? If so. Which drug?
Q2. What is your opinion for using estrogen therapy in treating this lady?
Q3. What are the adverse effects of estrogen in this lady?
Q4. How can you decrease the side effects of estrogen therapy in this lady?
Q5. What are the contraindications of estrogen?
Q6. Do you think that statins are good for the patient?
Q7. What is your opinion in using BAR or niacin?
Case 10: If the Ali's BP persists after lifestyle changes are made, how should he be managed?
Q1. Which drugs Beta blockers (ISA?), alpha blockers, mixed, thiazides?, CCBs, ACEI
Q2. Which diuretics do not affect blood lipids?
Q3. Are B. Blockers essential in Ali's condition?
What is your opinion in anti-oxidant in management of hyperlipidemic patients especially
who have developed CHD?
References:
1. The pharmacological basis of therapeutics By Goodman & Gillman's,
2006
2. Medical pharmacology and therapeutics By Derek Waller,2006
3. Basic and clinical pharmacology By Katzung, 2006
4. Modern pharmacology with clinical applications by Craig & Stitzel, 2004
5. Clinical pharmacy and therapeutics By Roger Walker,2003
6. Clinical pharmacology By George Carruthers, 2001
7. Clinical pharmacology By Bennet & Brown, 2003
8. Illustrated pharmacology By Bastawi and AbdelBary, 2003
9. Pharmacolgy and Pharmacotherapeutics By Satoskar, 2000.