2. Why Hypolipidemic Drugs?
• They can decrease the cases of atherosclerosis which in
turn will decrease the cardiovascular disease.
• Atherosclerosis is associated with elevated levels of certain plasma LPs,
especially the LP involved in cholesterol transport.
• For example: LDL; IDL; VLDL; TG & decreased HDL
3. What are lipoproteins?
• Lipoproteins are protein-lipid complexes, that help transport the
water insoluble lipids.
•Inner droplet of neutral (water-insoluble
core lipids); primarily triglycerides and
cholesteryl esters
•A solubilizing surface layer of
phospholipids and un-esterified
cholesterol
•Specific proteins (apo-lipoproteins)
attached to the outer lipid layer through
their specific lipophilic domains
6. Hyperlipidemias
• Hyperlipidemias are grouped according to their
lipid levels in
• hypercholesterolemia,
• hypertriglyceridemias, and
• mixed hyperlipidemias.
• Among these, hypercholesterolemia has the
strongest correlation to the risk for coronary heart
disease.
15. Statins-MOA
• Inhibit mevalonate synthesis by HMG-CoA-reductase
[RLS in cholesterol synthesis in liver]
• The number of high-affinity LDL receptors are
increased in liver.
• Thereby, increased clearance of VLDL remnants
[IDL] and LDL from blood.
• Higher dose of potent statins (Atorva..,Simva..) also
reduce TG levels due to elevated VLDL levels.
• Increases HDL levels in blood
16. Statins-- Therapeutic uses
• Treatment of primary hyperlipidemia (IIa, IIb
and V).
• Treatment of secondary hypercholesteronemia
(diabetes, nephrotic syndrome).
• Atorvastatin/Simvastatin: Efficacy > others:
reduces TG > others
• With Ca-channel blocker, used in hypertension
as well.
• Since it increases endothelium production and
NO production, beneficial role in CAD.
17. Statins-- Side effects
• Mild rise in aminotransferase
• Increase in CPK (creatine phosphokinase)
levels[10%] and myopathy.
• Myalgia [rhabdomyolysis]
• Risk of hepatotoxicity & myopathy following
drug interactions
• Headache, Nausea, bowel upsets, rashes
• Sleep disturbances
18. Resins
• Bile acids are needed for absorption of fats and
lipids from GIT.
• Resins bind to bile acids and similar steroids in
the intestine, bound complex excreted in feces.
• Reduce the availability of cholesterol for production
of plasma protein
• A compensatory increase in high-affinity LDL
receptors: elimination of LDL-cholesterol from blood
• To compensate the excreted bile acids, more
cholesterol is utilized in the synthesis of bile acids.
19.
20. Therapeutic uses and S/Es
Uses:
Hyperlipidemia
• Pruritus due to cholestasis & bile salt accumulation
Also in some diarrheas caused by bile acids.
• Suitable only when LDL-CH levels are raised (IIa, IIb,
and V). Can reduce risk of angina and MI in them.
ADR:
Bloating, constipation, & unpleasant taste (nausea)
• Impaired absorption of fat soluble vitamins & drugs
[digitalis, thiazides, warfarin, lovastatin]
21. Fibrates
• Bind the peroxime proliferator-activated-alpha [PPAR-
alpha] protein and regulate transcription of the genes
involved in lipid metabolism.
• Increases / activates the synthesis of the enzyme
LP lipase and induce the metabolism of VLDL.
• Decreases the release of free F A from adipose tissue
thus their levels in peripheral circulation are decreased.
• Also reduces hepatic TG levels.
• Reduce cholesterol production in liver.
• Reduce in LDL-cholesterol and increase in HDL levels.
22.
23. Fibrates—Clinical uses
Uses:
Hyperlipidemias with elevated of both LDL and
VLDL level
In treating severe hypertriglyceridemia (TG
>1000mg/dl), patients at risk for pancreatitis.
• Contraindicated in renal and/or hepatic
failure; should be avoided in pregnant women
and in children.
24. Fibrates—S/Es
• Nausea & GI upsets[common]
• Skin rash with Gemfibrozil
• Alopecia, myalgias, headache, impotence
• Decrease WBC or hematocrit (anemia)
• Potentiate the action of anticoagulants
• Risk of cholesterol gallstones esp. with
Clofibrate.
25. Niacin /Nicotinic acid
• A water soluble vitamin (B3); reduces plasma lipid
levels at high doses; the dose is usually not tolerated
thus use is not frequent.
• Directly reduces the secretion of VLDL from liver.
• Inhibits hepatic synthesis of TGs & cholesterol
• Reduced LDL: LDL-cholesterol
• HDL level is elevated (Best agent)
Uses:
1. Hypertriglyceridemia with high LDL-cholesterol.
2. HTG with low HDL levels.
26.
27. Niacin /Nicotinic acid—S/Es
• Cutaneous flushing [mediated by PGE] give NSAID
30 mins before therapy
• Dose dependent gut distress
• Pruritis and rashes in skins
• Serious hepatotoxicity (fulminant hepatic failure/ acute
liver failure) --dose dependant
• Hyperuricemia [20%]
• Moderate Carbohydrate intolerance
• Insulin resistance hyperglycemia in DM.
• Atrial tachyarrhythmias and atrial fibrillation
esp. in elderly patients.
28.
29. EZETIMIBE
• First compound approved for lowering total and LDL-C
levels that inhibits cholesterol absorption by
enterocytes in the small intestine.
• Lowers LDL-C levels by about 18% and is used
primarily as adjunctive therapy with statins.
• Rare allergic reactions are reported; no other
significant A/E.
• Available usually combined with statins (co-
formulation).