Dr Anshuman Parida
Department of Pharmacology
• Hypolipidemic agents, or antihyperlipidemic
• A diverse group of pharmaceuticals used in T/t
of high levels of fats (lipids), such as cholesterol,
in the blood (hyperlipidemia).
• They are also called lipid-lowering drugs.
Lipid transport and metabolism
• Lipids originate from two sources:
▫ Endogenous lipids : synthesized in the liver,
▫ Exogenous lipids: ingested and processed in
• Dietary cholesterol & triglycerides : packaged into
chylomicrons in the intestine into bloodstream via
• Liver synthesizes TG and cholesterol packages them as
VLDLs before releasing them into the blood
• VLDLs in muscle and adipose blood vessels, their TG are hydrolyzed
by LPL to fatty acids.
• The fatty acids that are released are taken up by the surrounding
muscle and adipose cells.
• During this process, the VLDLs become progressively more dense
and turn into LDLs
• Most LDLs taken up by Liver for disposal,
• some circulate and distribute cholesterol to the rest of the body
• HDLs, which are also secreted from the liver and intestine, have the
task of preventing lipid accumulation.
• They remove surplus cholesterol from tissues and transfer it to
LDLs that return it to the liver.
• Elevated concentrations of lipid i.,e, Hyperlipidemia
development of atherosclerosis and CAD.
• Dyslipidemia can be primary or secondary.
• Primary forms : genetically determined
• Secondary forms : Consequence of other conditions such
as Diabetes mellitus,
Chronic renal failure,
Administration of drug…
Management of Dyslipidemia
• Drug therapy to lower plasma lipids is only one approach
• Used in addition to dietary management
• Correction of other modifiable cardiovascular risk
• Several drugs are used to decrease plasma LDL-CHO
• HMG - Co A Reductase inhibitors ( Statins ) :
• Bile acid binding resins :
Cholestyramine, Colestipol, Colesavelam.
• Inhibitors of intestinal absorption of cholesterol
: Stanol esters , Ezetemibe
• Activators of Lipoprotein lipase (LPL) (Fibrates)
Gemifibrozil, Bezafibrate, Fenofibrate, and
• Inhibitor of VLDL secretion and lipolysis :
Niacin (Nicotinic acid)
• New drugs (CETP Inhibitors) :
Class: HMG-CoA reductase inhibitors
• Mechanism: ↓rate-limiting step in cholesterol synthesis.
• Clinical use: ↓ LDL, ↓ triglycerides
• Side effects: H : Hepatotoxicity
M : Myositis,rhabdoMyolysis
G : ↑ FPG
C : ↑ Creatinine phosphokinase
A : HeadAche, Joint pain
R : Rash
10-80 10-40 5-40 10–40 5–20 1–4 mg 10-80
complete Incomplete, Varies from 45-75%
1-3 1-3 18–24 1-4 2-3 12 14
CYP CYP2C9 CYP3A4
DRC Non linear linear
35% <25% 51-55% 40% 40% 40% 51-55%
C/I - 80
• Pregnancy & lactation
• Children < 7-8 years
• Active liver diseases
• Mechanism: binds with PPAR α
↑ lipoprotein lipase → ↓ VLDL
• Clinical use: Elevated TG and remnants.
• Side effects: GI upset (dyspepsia),
• Drug interaction: Warfarin ,OHA
Drug Gemfibrozil Fenofibrate Benzafibrate Clofibrate
Dose 600 mg BD 145mg QID 200 mg TDS
T ½ (hours) 1.5 20 18-24
Tightly bound to plasma protein
Excretion Kidney, liver urine, faeces Kidney
Special feature Trial for
• Increased risk of myopathy when combined with
• Displace drugs from plasma proteins( e.g. oral
anticoagulants and oral hypoglycemic drugs).
• 1- Patients with impaired renal functions.
• 2- Pregnant or nursing women.
• 3-Preexisting gall bladder disease
Class : Nicotinic Acid
• Mechanism: ↓ fatty acid release from adipose
tissue, ↓ hepatic synthesis of LDL
• Clinical use: ↑ HDL, ↓ LDL, ↓TG
• Side effects: Skin flushing, paresthesias,
pruritus, GI upset, ↑LFTs, hyperglycemia,
• Prevention of side effects: Aspirin
• Wide spectrum antilipidemic drugs
• Most effective in reducing TG level.
• Dose: Start with 100 mg TDS, gradually increase
to 2–4 g per day in divided doses.
• To be taken just after food to minimize flushing
Class: Cholesterol absorption inhibitors
• Mechanism: inhibits the luminal cholesterol
uptake by inhibiting the transport
protein on NPC1L1
• Clinical use: ↓ LDL
• Side effects: Diarrhea, abdominal pain
• Reduces both dietary and billiary cholesterol.
• Dose : 10 mg OD
• T 1/2 ~ 22 hours
• Long half-life:
▫ Permits once-daily dosing
▫ May improve compliance
Class: Bile acid resins
• Mechanism: Bind intestinal bile acids → ↓bile acid
stores & ↑ catabolism of LDL from plasma.
• Clinical use: ↓ LDL
• Side effects: Constipation,
↑ Gallstone formation,
↓ Absorption of drugs
ADEK vitamins from the small intestine.
• Dose : 4 to 8 g OD/BD, max dose 24 g/d.
• Drug interactions : due to the risk of decreased
absorption of these drugs.
Digitalis, Estrogens and progestins,Oral diabetes drugs,
Thiazide-type diuretic pills,Thyroid medication
▫ 1- Complete biliary obstruction( because bile is not
secreted into the intestine).
▫ 2- Chronic constipation.
▫ 3-Severe hypertriglyceridemia(TG >400 mg/dL)
Class : CETP INHIBITORS
• Torcetrapib and Anacetrapib banned.
• Dalcetrapib (Clinical trails)
• Anacetrapib – Increases HDL-C by 129%
• Obicetrapib (TA-8995), Phase II results reported in
• Cholesteryl ester transfer protein (CETP) Facilitates
transfer of cholesteryl esters (CE)
from HDL-C to LDL-C, VLDL-C during “reverse
• Increased VLDL during treatment of
hypercholesterolemia with resins.
• Combined increase in LDL & VLDL.
• High LDL or VLDL not normalized with a single drug.
• Severe hypertriglycerdemia or hypercholesterolemia.
• To take lower doses of each drug