Download Antihyperlipoproteinemic Drugs

Antihyperlipoproteinemic Drugs
Antihyperlipoproteinemic
Drugs
Niacin (Nicotinic Acid)
Fibrates: Gemfibrozil &
Clofibrate
Mechanism of Action
Indications
AE
- Water soluble vitamin that
inhibits lipolysis in adipose tissue
and so lowers free FA in
circulations, which is necessary
for VLDL and so LDL synthesis.
So, both TAG (in VLDL) and
cholesterol (in VLDL and LDL
goes down.
- Increases tissue plasminogens
and lowers plasma fibrinoges
- Tx. of type IIb and
type IV
hyperlipidemia
- Raise plasma HDL
levels (most effective)
- Decrease plasma TAG by
increasing lipoprotein lipase
activity and so hydrolyzing TAG
in VLDL and Chylomicrons
- Moderate increase in HDL
- Inhibits cholesterol synthesis in
liver and increases biliary
excretion of cholesterol so
decreased plasma cholesterol
- Lowers plasma fibrinogen levels
- Tx. Of type III, type
IV and type V
hyperlipidemia
- Decreased MI
incidence had been
seen w/ this drug
- Intense cutaneous flush
which can be decreased
by taking aspirin prior to
taking niacine
- Pruritus
- Nausea
- Abdominal pain
- Hyperuricemia & gout
- Hepatotoxicity
- Impaired glucose
tolerance
- Activation of peptic ulcer
- Mild GI disturbance
- Gall stone formation b/c
of increased biliary
cholesterol excretion
- Myositis, muscle
weakness and
tenderness, myalgia
- Claudications
- Thrombosis (??)
- Decreased libido
CI
Other
Should be
avoided in
pregnancy b/c
of teratogenic
effects
Shows
decreased
mortality
Should not be
used in pt. w/
hepatic and
kidney
dysfunction
and should be
avoided in pt.
w/ pre-existing
gall bladder
disease
Lowers
coumarin
clearance and
so increases
its
anticoagulant
effects, so
should lower
the coumarin
dose when
taking this
drug
Bile acid binding resins:
Cholestyramine
Colestipol
- Binds to (-)vely charged bile
acids and bile salts and increases
their excretion in feces and so
decreases bile acid return to
liver, so liver uses cholesterol to
make more bile acid and bile
salt so the intracellular
cholesterol goes down and so
LDL receptors go up, which
increases uptake of circulating
LDL and so plasma cholesterol
goes down.
HMG CoA Reductase
Inhibitors:
Lovastatin
Simvastatin
Pravastatin
Fluvastatin
- Inhibits HMG CoA Reductase,
which is necessary for
cholesterol synthesis. So,
intracellular cholesterol goes
down. As a result, LDL
receptors goes up and uptake of
circulating LDL by cell goes up
lowering plasma cholesterol
- HDL may go up in some pt.
- Small decrease in TAG
- Macrophages ingest oxidized
LDL and become foam cells,
which then accumulates in
vessels and forms atherosclerotic
plaque, so probucol inhibits
oxidation of LDL and so slows
development of atherosclerosis
Probucol
- DOC in tx. of type IIa
and type IIb
hyperlipidemia. (it has
little effects in pt. who
are homozygous of
type IIa
hyperlipidemia that is
they have no
functional LDL
receptors)
- Cholestyramine
relieves pruritus
caused by bile acid
accumulation in pt. w/
biliary obstruction
- Tx. of all kinds of
hyperlipidemias
- Less effects in pt.
homozygous type IIa
hyperlipidemia
-
Constipation, bloating
Flatulence
Nausea
Abdominal pain
Impaired absorption of
fat soluble vitamins (vit.
A, D, E and K)
- Reduced absorption of
folic acid and ascorbic
acid
- Interfere w/ intestinal
absorption of other drugs
- limited use in type IIa
and type IIb
hyperlipidiemia b/c it
also decreases HDL
which is a risk factor
for atherosclerosis
- claimed to reduce fq of
new angioplasty
- Mild GI Disturbance
- Prolongation of QT
interval
-
Fewer AEs
Increased liver enzymes
Myopathy
Rhabdomyolysis
GI disturbance
Headache
Increases coumarin
levels
Should be
taken w/
meals
CI in
pregnancy and
nursing
mothers, and
shouldn’t be
used in
children and
teenagers
CI in pt who
have
abnormally
long QT
interval
-Accumulates
in adipose
tissue for
months
- Should be
taken w/ food
Combination Drug Therapy:
-
Type II hyperlipidemias can be treated with combination of Niacin and Bile acid binding agent such as cholestyramine.
The combination of HMG CoA Reductase inhibitors and bile acid binding agents can be used to lower LDL cholesterol.
Triple drug combination is possible but increases risk of kidney failure
Types of Hyperlipidemias
Type of Hyperlipidemia
Type I: Familial Hyperchylomicronemia
Type IIA: Familial Hypercholesterolemia
Problem
Increased chylomicrons and so increased
TAG
Blocked degradation of LDL so, elevated
LDL w/ normal VLDL (increased plasma
cholesterol)
Type IIB: Familial Combined (Mixed) Hyperlipidemia
Increased VLDL and LDL, so increased
plasma TAG and cholesterol
Type III: Familial Dysbetalipoproteinemia
Increased IDL so increased TAG and
cholesterol
Type IV: Familial Hypertriglyceridemia
Increased VLDL and so increased TAG
Type V: Familial Mixed Hypertriglyceridemia
Increased VLDL and Chylomicrons, so
elevated cholesterol but greatly increased
TAG
Treatment
No drug therapy
Low fat diet
Bile acid binding resins
HMG CoA Reductase inhibitors
Niacin (in homozygous)
Low saturated fat and low cholesterol diet
Niacin
Bile acid binding resins
HMG CoA Reductase inhibitors
Low saturated fat and low cholesterol diet
Fibric Acid
HMG CoA Reductase inhibitors
Diet modification
Fibric Acid
Niacin
Diet modification
Fibric Acid
Niacin
HMG CoA Reductase inhibitors
Diet modification