Antilipemic drugs

dr. Ave Olivia Rahman, MSc

Bagian Farmakologi FKIK UNJA
 Antilipemic drugs
• are used to lower abnormally high blood levels
of lipids (cholesterol, triglycerides,
phospholipids)
• When serum lipid levels are elevated  The
risk of developing CAD increases
• Drugs are used in combination with
– lifestyle changes (such as proper diet, weight loss,
and exercise)
– treatment of an underlying disorder causing the
lipid abnormality to help lower lipid levels.
 The classes of antilipemic drugs
1. Bile-sequestering drugs
2. Fibric acid derivatives
3. 3 -hydroxy-3 -methylglutaryl coenzyme A
(HMG-CoA) reductase inhibitors
4. Nicotinic acid
5. Cholesterol absorption inhibitors.
 1. Bile-sequestering drugs
• Include : cholestyramine, colestipol, and
colesevelam
• Bile-sequestering drugs aren’t absorbed from
the GI tract.
• lower blood levels of low -density lipoproteins
(LDLs).
 Pharmacodynamics
• These drugs combine with bile acids in the intestines
to form an insoluble compound that’s then excreted
in stool
• The decreasing level of bile acid in the gallbladder
triggers the liver to synthesize more bile acids from
their precursor, (cholesterol)  blood cholesterol
levels decrease.
• Because the small intestine needs bile acids to
emulsify lipids and form chylomicrons, absorption of
all lipids decreases until the bile acids are replaced.
 Pharmacotherapeutics
• Drugs of choice for treating type IIa
hyperlipoproteinemia (familial
hypercholesterolemia) when the patient can’t
lower his LDL levels through diet alone.
 Drug interactions
• They may bind with acidic drugs in the GI tract, decreasing their
absorption and effectiveness. Acidic drugs likely to be affected
include barbiturates, phenytoin, penicillins, cephalosporins,
thyroid hormones, thyroid derivatives, and digoxin.
• Bile-sequestering drugs may decrease absorption of propranolol,
tetracycline, furosemide, penicillin G, hydrochlorothiazide and
gemfibrozil.
• Bile-sequestering drugs may reduce absorption of lipid-soluble
vitamins, such as vitamins A, D, E, and K. Poor absorption of
vitamin K can affect prothrombin times significantly, increasing
the risk of bleeding.
 2. Fibric acid derivatives
• Fibric acid is produced by several fungi.
• Include : fenofibrate and gemfibrozil
• To reduce high triglyceride levels and, to a
lesser extent, high LDL levels.
• Fenofibrate and gemfibrozil are absorbed
readily from the GI tract and are highly protein
-bound
 Pharmacodynamics
• Exact mechanism of action isn’t known, may :
– Reduce cholesterol production early in its
formation
– Mobilize cholesterol from the tissues
– Increase cholesterol excretion
– Decrease synthesis and secretion of lipoproteins
– Decrease synthesis of triglycerides.
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• Gemfibrozil produces two other effects:
– It increases high -density lipoprotein (HDL) levels
in the blood
– It increases the serum’s capacity to dissolve
additional cholesterol.
 Pharmacotherapeutics
• Primarily to reduce triglyceride levels,
especially very low density triglycerides,
• Secondarily to reduce blood cholesterol levels.
• Typically used to treat patients with types II,
III, IV, and mild type V hyperlipoproteinemia.
 Drug interactions
• Fibric acid drugs may displace acidic drugs, such as
barbiturates, phenytoin, thyroid derivatives, and
cardiac glycosides.
• The risk of bleeding increases when fibric acid
derivatives are taken with oral anticoagulants.
• Fibric acid derivatives can lead to adverse GI effects.
• The hypoglycemic effects of repaglinide may be
increased and prolonged if taken with gemfibrozil.
• Use of fibric acid derivatives and HMG-CoA reductase
inhibitors may increase the risk of rhabdomyolysis.
 3. HMG-CoA reductase inhibitors
• Also known as the statins
• Include atorvastatin, fluvastatin, lovastatin,
• Lower lipid levels by interfering with
cholesterol synthesis.
• Inhibit the enzyme responsible for the
conversion of HMGCoA to mevalonate, an
early step in the synthesis of cholesterol.
 Pharmacotherapeutics
• Primarily to reduce LDL cholesterol and total
blood cholesterol levels.
• These agents also produce a mild increase in HDL
cholesterol levels.
• Statins are used to treat primary
hypercholesterolemia (types IIa and IIb).
• Because of their effect on LDL and total
cholesterol, these drugs are also used to reduce
the risk of CAD and to prevent MI or stroke in
patients with high cholesterol levels.
 Drug interactions
• Taking a statin drug with amiodarone, clarithromycin,
cyclosporine, erythromycin, fluconazole, gemfibrozil,
itraconazole, ketoconazole, or niacin increases the risk
of myopathy or rhabdomyolysis (a potentially fatal
breakdown of skeletal muscle, causing renal failure).
• Lovastatin, rosuvastatin and simvastatin may increase
the risk of bleeding when administered with warfarin.
• All of these drugs should be administered 1 hour
before or 4 hours after the administration of bile-
sequestering drugs (cholestyramine, colesevelam, and
colestipol).
 Adverse reactions
• Alter liver function studies, Myalgia, vomiting,
diarrhea, abdominal pain, flatulence, and
constipation.
 4. Nicotinic acid
• Also known as niacin
• Is water-soluble vitamin that decreases
cholesterol triglyceride, and apolipoprotein B-
100 levels and increases the HDL level
 Pharmacodynamics
• Is unknown
• it may work by :
– Inhibiting hepatic synthesis of lipoproteins
that contain apolipoprotein B-100,
– Promoting lipoprotein lipase activity
– Reducing free fatty acid mobilization from
adipose tissue,
– Increasing fecal elimination of sterols.
 Pharmacotherapeutics
• usually used in comb ination with other drugs to lower
triglyceride levels in patients with type IV or V
hyperlipidemia who are at high risk for pancreatitis
• to lower cholesterol and LDL levels in patients with
hypercholesterolemia.
• It may also be used with other antilipemics to boost
HDL levels.
• Contraindicated in patients who are hypersensitive to
nicotinic acid, hepatic dysfunction, active peptic ulcer
disease, or arterial bleeding.
 Adverse reactions
• May produce vasodilation and cause flushing
• Hepatotoxicity
• Nausea, vomiting, diarrhea, and epigastric or
substernal pain
 Drug interactions
• Together, nicotinic acid and an HMG-CoA
reductase inhibitor may increase the risk of
myopathy or rhabdomyolysis.
• Bile-sequestering drugs (cholestyramine,
colesevelam, and colestipol) can bind with
nicotinic acid and decrease its effectiveness.
 5. Cholesterol absorption inhibitors
• inhibit the absorption of cholesterol and related
phytosterols from the intestine.
• Include : Ezetimibe
• Is highly bound to plasma proteins
• Ezetimibe reduces blood cholesterol levels by
inhibiting the absorption of cholesterol by the
small intestine decrease in delivery of
intestinal cholesterol to the liver, reducing
hepatic cholesterol stores and increasing
clearance from the blood.
 Pharmacotherapeutics
• Primary hypercholesterolemia and homozygous
sitosterolemia (hereditary hyperabsorption of
cholesterol and plant sterols).
• Primary hypercholesterolemia and homozygous
familial hypercholesterolemia (combination with
hmg-coa reductase inhibitors)
• Lower total cholesterol and LDL cholesterol, and
increase HDL cholesterol (when maximum -dose
HMG-CoA reductase inhibitor therapy has been
ineffective)
 Adverse reactions
• fatigue
• abdominal pain and diarrhea
• pharyngitis and sinusitis
• arthralgia
• back pain
• cough.
 Drug interactions
• Ezetimibe administered with cholestyramine
may lead to decreased effectiveness of
ezetimibe.
• Ezetimibe administered with cyclosporine,
fenofibrate, or gemfibrozil leads to increased
levels of ezetimibe
Thank you