25.pptabacdbwbbysbehabsvhwhwhhwhhhsvyshebsbeb

Jbdufzugxub v

1. Hypolipidemic
Drugs and plasma
expanders
Dr. Rishi Pal
Assistant Prof.
Deptt. of Pharmacology

2. Cholesterol
•Criticalsubstrateforthebody:
–Fundamentalbuildingblockofsteroid
hormones
–Essentialforbuildingcellmembranes,the
myelinsheath,andthebrain
–Corecomponentofbilesalts,whichhelps
indigestdietaryfats
29-2

3. Lipoproteins
•There are several
different lipoproteins:
–Low-density lipoprotein (LDL)
–Very-low-density lipoprotein (VLDL)
–High-density lipoprotein (HDL)
29-3

4. Triglycerides
•Main form of fat from diet
•Provide body with energy
•Chylomicrons:
–Very large lipoproteins that deliver
triglycerides to muscle and fat tissue
29-4

5. © 2012 The McGraw-Hill Companies, Inc. All rights reserved.
1-5

6. © 2012 The McGraw-Hill Companies, Inc. All rights reserved.
1-6

7. Hypolipidemic Drugs
•There are five
groups of drugs
used in the
management of
hyperlipidemia:
–HMG-CoA reductase
inhibitors
–Cholesterol absorption
inhibitors
–Bile acid sequestrants
–Fibric acid derivatives
–Nicotinic acid
29-7

8. © 2012 The McGraw-Hill Companies, Inc. All rights reserved.
1-8

9. © 2012 The McGraw-Hill Companies, Inc. All rights reserved.
Atherosclerosis
•Atherosclerosis is a
progressive condition
that leads to CAD and
PAD.
•Fat buildup inside the
arteries—plaque
•CAD—coronary artery
disease
•PAD—peripheral
artery disease
29-9

10. © 2012 The McGraw-Hill Companies, Inc. All rights reserved.
1-10

11. © 2012 The McGraw-Hill Companies, Inc. All rights reserved.
Atherosclerosis
•There are two types
of plaque buildup:
–Stable
–Unstable
•Plaque buildup can
block arteries,
causing:
–Angina
–TIA
–Stroke
–Intermittent
claudication
29-11

12. Monitoring the Disease
•Risk factors for
atherosclerosis
–Age
–History of smoking
–Hypertension
–Premature menopause
–Obesity
–Diabetes mellitus
–Hyperthyroidism
29-12

13. Monitoring the Disease
•The goals of treatment are:
–Lowering LDL cholesterol
–Reducing total serum cholesterol and
triglycerides
–Increasing HDL cholesterol
29-13

14. © 2012 The McGraw-Hill Companies, Inc. All rights reserved.
1-14

15. HMG-CoA Reductase inhibitors
•Atorvasatatin
•Simvastatin
•Lovastatin
•Pravastatin
•Fluavastatin
•Rosuvastatin

16. Bile acid binding resins
•Cholestyramine
•Colestipol
•Colesevelam

17. Intestinal cholesterol absorption
inhibitors
•Stanol esters
•Ezetimibe

18. Activators of lipoprotein lipase
(Fibrates)
•Gemfibrozil
•Benafibrate
•Fenofibrate
•Ciprofibrate

19. Inhibitor of VLDL secretion and
lipolysis
•Niacin (Nicotinic acid)
Miscellaneous:Gugulipid and fish oil
derivatives

20. © 2012 The McGraw-Hill Companies, Inc. All rights reserved.
Fibrates
Others
Resins
Statins
LIPID-LOWERING
DRUGS

21. HMG-CoA Reductase Inhibitors
•Alsoreferredtoasstatins
•MOA—inhibitenzymethatcauses
cholesterolsynthesis
•IND—adjuncttodietarytreatmentto
decreasetotalserumandLDL
cholesterol:
–Reduce LDL level up to 30%
–Raise HDL level up to 20%
29-21

22. HMG-CoA Reductase Inhibitors
•Anearly,veryimportantstepinthisprocessis
theconversionofacetyl-CoAmoleculesinto
HMG-CoA,whichisthenconvertedtomevalonic
acidbyHMG-CoAreductase.Mevalonicacidis
arate-limitingpivotalstepinsteroidand
cholesterolbiosynthesis
•Thelivermakestwo-thirdsofthedaily
cholesterolrequirement.
1-22

23. HMG-CoA Reductase Inhibitor
•AllofthestatinsreduceLDLupto30percent.Whena
greaterreductionofLDLisrequired,simvastatin(Zocor),
atorvastatin(Lipitor),androsuvastatin(Crestor)reduce
morethan45percent;infact,rosuvastatinand
atorvastatinhavebeendemonstratedtoreduceupto60
percent.
•AllofthestatinsraisetheHDLlevelupto20percent.
Again,simvastatin(Zocor),atorvastatin(Lipitor),and
rosuvastatin(Crestor)increaseHDLmorethan30
percent.
1-23

24. © 2012 The McGraw-Hill Companies, Inc. All rights reserved.
1-24

25. HMG-CoA Reductase Inhibitors
•Adverse effects:
–Headache, dizziness, alteration of taste,
insomnia, abdominal cramping and
photosensitivity
•May cause myalgias, leg ache, and
muscle weakness
•Contraindicated during pregancy
29-25

26. Cholesterol Absorption
Inhibitors
•Ezetimibe:
–MOA—blocks absorption of cholesterol
in the intestines
•Decreases VLDL
•Decreases circulating LDL cholesterol
–IND—treatment of hyperlipidemia in
conjunction with diet alteration
29-26

27. Cholesterol Absorption
Inhibitors
•Ezetimibe:
–Modestly reduces total cholesterol, LDL,
and triglyceride blood levels
–Ideal to combine with other
hypolipidemic drugs
–Adverse effects—abdominal pain,
fatigue, coughing, diarrhea, back pain,
and arthralgia
29-27

28. Bile Acid Sequestrants
•MOA—bind bile salts and cholesterol
in the GI tract, preventing absorption
of both
•IND—hyperlipidemia:
–Increased elimination of bile salts, cholesterol,
and other fats in the faeces.
–Adverse effects include GI disturbances,
severe constipation, and fecal impaction.
–Most serious adverse effect is intestinal
obstruction.
29-28

29. Nicotinic Acid
•MOA—affects cholesterol synthesis
through a G proteins coupled receptor:
–Inhibits triglyceride lipase
–Stimulates lipoprotein lipase
–Decreases free fatty acid release and
removes triglycerides
•IND—hyperlipidemia
•Adverse effects—flushing, nausea,
vomiting, and diarrhea
29-29

30. Fibric Acid Derivatives (Fibrates)
•Gemfibrozil:
–MOA—inhibits breakdown of fat into
triglycerides, and limits liver production
of triglycerides
–IND—to decrease triglycerides
–Adverse effects—nausea, vomiting,
diarrhea, and flatulence
29-30

31. Gugulipid
•Consists of Z and E gugulsterone
•Inhibit cholestrol biosynthesis and also
enhance rate of cholesterol excretion
•Dose 25 mg 3 times a day
•ReducedtotalCH,LDL-Cwithan
elevationofHDL-C
•It is well tolerated, no side effect, except
loose stool

32. Fish oil derivative
•Omega-3-fatty acids
•Eicosa-pentanoic and docosa-hexanoic
acid
•Prophylaxis use in high risk patient of CAD
•Usually formulated with vit.E

33. Combination drug therapy
•Bile acid binding resins+Fibrates
•Bile acid binding resins+Niacin
•Bile acid binding resins+Statins
•Bile acid binding resins+Niacin+ Statins
•Niacin+Statin (Atorva 10+ Nia 500)
•Statins+Ezetimibe
•Statins+Fibrate

34. Hypolipidemic Drugs
29-34

35. Preferred Therapy
•All hypolipidemic drugs are indicated as
adjunctive therapy to reduce elevated
cholesterol levels.
•HMG-CoA reductase inhibitors are the
most prescribed.
•Cholestyramine can also be used in the
treatment of partial biliary obstruction.
29-35

36. Contraindications
•Systemic hypolipidemic drugs should not
be used in patients with liver dysfunction.
•Bile acid sequestrants should not be used
in patients with biliary obstruction.
•Statins should not be used in pregnant
women.
29-36

37. Drug Interactions
29-37

38. New drugs
•Cholesteryl ester transfer protein (CETP)
•Torcetrapib
•Anacetrapib

39. Blood substitutes and
plasma expenders

40. Hypovolaemia
•Shock is a state of acute circulatory failure
•So, it is essential to restore intravascular
blood volume as quickly as possible
•Intravenous fluid therapy

41. Types of fluid used for
replacement
•Whole blood and plasma
•Plasma substitute:
•a) Colloidal: Dextran, hydroxyethyl starch
polyvenyl pyrrolidone, oxypolygelatin.
b) crystalline: NaCl, dextrose solution

42. Desirable properties of plasma
expenders
1.Should exert oncotic pressure comparable to plasma.
2.Should retain in circulation and not leak out in tissues
or too rapidly disposed.
3.Should be pharmacodynamically inert.
4.Should not be pyrogenic or antigenic
5.Should not interfere with grouping and cross matching
of blood.
6.Should be stable and easily sterilizable and cheap.

43. Substance employed are
•Human albumin
•Dextran
•Polygeline
•Hetastarch

44. Albumin
•100mlof20%humanalbuminsolutionisosmotic
equivalentofabout400mloffreshfrozenplasmaor800
mlofwholeblood.
•Notinterferewithbloodgroupandcoagulationprocess.
•Crystalloidsolutionsmustbeinfusedconcurrentlyfor
optimumbenefit.
•Itisexpensive.

45. Dextran
•Dextran-40:10%indextroseorinNaCl
•Dextran-70,expendsplasmavolumefor24hr.
•500-1000mlin30min.and100mlbycontinuous
infusionfor2-3days.
•BecarefulinpatientsofRenalimpairment,CHFor
Polycythaemia.
•Dextran-70&dextran110:6%indextroseorinNaCl,
usedforhypovolaemicorhaemorrhagicshock

46. Polyvenylpyrrolidone
•It is synthetic water soluble preparation
with MW 35,000-40,000.
•It is sterile solution in buffered
physiological saline
•It has tendency to bind with insulin and
penicillin

47. Gelatin
•MW 30,000
•500-1000 ml of 3.5-4% used in low blood
volume
•Expends plasma volume for 12 hr
•More expensive than dextran

48. Contraindications
•Severe anemia
•Cardiac failure
•Pulmonary edema
•Liver disease
•Renal insufficiency

49. Electrolyte and water
replacement
•Normal saline (0.9%)
•Dextrose 5%