Transcript The Antihyperlipidemic Medications Classifications of Lipoproteins Chylomicrons

The Antihyperlipidemic
Medications
 Classifications
of Lipoproteins
– Chylomicrons
 Formed
in the mucosal cells of the
gut
 Protein coated dietary lipids
 Carried
in the blood to fat depots
and transported across the
vasculature with the help of
Capillary-Bound LPL
 Chylomicron remnants goes back
to the liver to be used to
synthesize TGs
 Very
Low Density Lipoproteins
(VLDL)
– Triglyceride rich particle
– Made in the liver
– VLDL is the transport form for
TGs made in the liver going to the
periphery
Cholesterol
containing
particle
LPL transports TGs into fat
depots
Remainder is a cholesterol
rich particle now called LDL
 Low
Density Lipoprotein (LDL)
 Contains
the major portion of the
plasma cholesterol
 Associated with a higher risk for
CAD
In
the liver LDL is recycled for
its cholesterol content
LDL in the liver acts to
regulate liver uptake of
additional LDL
 High
Density Lipoprotein (HDL)
 These
particles scavenge cholesterol
from the peripheral vessels
 Carries cholesterol back to the liver
to be used for steroid synthesis,
hormone synthesis or the making of
bile salts
 Types
of hyperlipoproteinemias
 Type
I - Idiopathic Familial Variety
– Decreased VLDL, LDL, & HDL
– Elevated TGs, Chylomicrons &
cholesterol
 Type
IIa - Essential Familial
Variety
 Elevated
LDL, TGs & Cholesterol
 Type
IIb - Familial Combined
Variety
 Elevated
LDL & VLDL
 Type
IV - Endogenous
Hypertriglyceridemia
 Elevated
VLDL, TGs, &
Cholesterol
 Early CAD
 Positive family history for an MI
The Antihyperlipidemic
Drugs
 HMG-CoA
Reductase Inhibitors
 The Fibric Acids
 Bile Acid Binding Resins
 Nicotinic Acid
HMG-CoA Reductase
Inhibitors
 Lovastatin
(Mevacor)
 Simvastatin (Zocor)
 Mevastatin (Compactin)
 Pravastatin
Mechanism Of Action
 HMG-CoA
 Blocks
Reductase Inhibitors
the synthesis of cholesterol
in the liver by inhibiting the rate
limiting enzyme called HMG-CoA
Reductase
 There
is a compensatory drop
in plasma LDL due to the upregulation of the LDL receptor
and enhanced clearance of
LDL from the plasma

These medications may lower the
cholesterol content of the VLDL
particle such that when VLDL
disposes of its TGs becoming LDL,
there is an enhanced attraction for the
cholesterol poor LDL particle and its
receptor - greater LDL clearance
Adverse Side Effects
 Flatulence
& Diarrhea
 Dyspepsia (Indigestion)
 Headaches
 Elevations of the liver enzymes CPK, LDH, and AST - due to
hepatotoxicity
Medical Uses
 To
treat hypercholesterolemia
(>250 mg/dl)
 Patients with elevated LDL,
VLDL & TGs
The Fibric Acids
 Gemfibrozil
(Lopid)
 Clofibrate (Atromide-S)
Mechanisms of Action
 Decrease
TG synthesis
 Decrease liver lipoprotein
synthesis
 Decrease the excretion of
lipoproteins from the liver,
especially VLDL
 Decrease
the synthesis of
cholesterol
 Increase the production of sterols
 Increases the blood levels of HDL
Medical Uses
 Lower
cholesterol
 Lower serum triglycerides
 Lower VLDL levels
 Lower LDL levels
 These drugs are cardioprotective
Adverse Side Effects
 GI
distress - diarrhea, nausea,
vomiting
 Alopecia - loss of hair
 lower testosterone levels and
impotence
 Gall
stone formation
 Hepatotoxic - liver enzymes LDH, CPK, & AST
Bile Acid Binding Resins
 Cholestyramine
(Questran)
 Colestipol (Colestid)
Mechanism of Action
 Bind
bile salts in the gut
 Bile Acid Binding Resins are not
absorbed across the gut into the
blood - bile and cholesterol are
irreversibly bound in the gut and
disposed of in the feces
 The
net effect - causes the liver to
scavenge more cholesterol from
the body to make additional bile
salts
 Liver up-regulates the LDL
receptors clearing more LDL from
the blood
Adverse Side Effects
 Nausea,
Vomiting
 Indigestion
 Flatulence
 Constipation
 Binds to other medications
Nicotinic Acid
 Mechanism
Inhibits
of Action
the liver from
secreting VLDL
Reduces the blood levels of
LDL
Inhibits
the destruction of
HDL thus allowing a
permissive rise in HDL
Niacin increases the excretion
of sterols in the feces thus
using up more cholesterol
Adverse Side Effects
 Flushing
 Vomiting
 Nausea
 Dyspepsia
 Flatulence
Medical Uses
 To
reduce VLDL
 To reduce LDL
 To increase HDL
 Given to most hyperlipidemics