This PowerPoint presentation offers a concise exploration of vital hypolipidemic drugs utilized in dyslipidemia management and cardiovascular disease prevention. It provides a succinct overview of dyslipidemia's impact on cardiovascular health, emphasizing elevated cholesterol's role in atherosclerosis and coronary artery disease. It outlines mechanism of action, pharmacokinetic details, commonly prescribed drugs (e.g., atorvastatin, simvastatin, rosuvastatin), and their efficacy, safety, and adverse effects are discussed.

1. HYPOLIPIDEMIC
DRUGS/STATIN

2. •↑ risk of
atherosclerosis is
associated with
hypercholesterolemia
•↑ risk of
cardiovascular and
cerebrovascular
diseases
•Treatment goal is to ↓
LDL cholesterol and
atheroma plaque
formation

3. HMG-COA REDUCTASE
INHIBITORS
Drugs:
Atorvastatin
Simvastatin
Rosuvastatin
Lovastatin
Pravastatin
Fluvastatin
Pitavastatin
The most effective and
best tolerated agents
to treat
dyslipidemias,
especially
elevated LDL-C

4. MECHANISMS
HMG-CoA reductase inhibition, results in:
↓ liver cholesterol
↑ LDL-receptor expression
↓ plasma LDL
↓ VLDL synthesis results in: ↓ triglyceridemia

6. SIDE EFFECTS
•Myalgia, myopathy (check creatine kinase)
•Rhabdomyolysis
•Hepatotoxicity (check liver function tests)
•Safety of statins during pregnancy has not been
established. Women wishing to conceive and
nursing mothers should not take statins
•During their childbearing years, women taking
statins should use highly effective
contraception.

7. DRUG INTERACTION
•Gemfibrozil (↑ rhabdomyolysis)
•Cytochrome P450 inhibitors enhance toxicity of
statins

8. BILE ACID SEQUESTRANTS
Drugs
Cholestyramine
Colestipol
Colesevelam
Probably safest lipid-lowering drugs
(not absorbed systemically)
Recommended for patients 11–20 years
of age

9. MECHANISM
Complexation of bile salts in the gut, results in:
•↓ enterohepatic recirculation of bile salts
•↑ synthesis of new bile salts by the liver
•↓ liver cholesterol
•↑ LDL-receptor expression
•↓ blood LDL

10. SIDE EFFECTS
•↑ VLDL and triglycerides
•Gastrointestinal disturbances: : bloating,
dyspepsia, constipation
•Malabsorption of lipid-soluble vitamins
•Hyperglycemia

11. •Drug interactions with orally administered
drugs (warfarin, thiazides, digoxin, etc.)
•Cholestyramine and colestipol bind and
interfere with absorption of many drugs;
administer all other drugs either 1 h before or
3–4 h after dose of a bile acid resin
•Contraindication: hypertriglyceridemia

12. NICOTINIC ACID (NIACIN,
VITAMIN B3)
Mechanism: inhibition of VLDL synthesis, results
in:
•↓ plasma VLDL
•↓ plasma LDL
•↑ plasma HDL
•inhibits intracellular lipolysis
by lipases in adipocytes
and decreases flow of FFAs from adipose tissue
to liver
Favorably affects all
lipid parameters;
most effective agent
for increasing HDL-C;
also lowers
triglycerides and
reduces LDL-C

13. SIDE EFFECTS
•Should not be taken by pregnant women
•Flushing (PG release—cutaneous vasodilation),
pruritus, and dyspepsia
•Rarer episodes of nausea, vomiting, and
diarrhea
•Hepatotoxicity, manifested as ↑ serum
transaminases
•Hyperglycemia and niacin-induced insulin
resistance; in patients with known or suspected
diabetes, blood glucose levels should be
monitored at least weekly until stable

14. CONTRAINDICATION(S)
•Concurrent use of niacin and a statin can cause
myopathy
•Any history of peptic ulcer disease
•Gout (compete with uric acid for excretion by
kidneys)

15. FIBRATES (LIPOPROTEIN-
LIPASE ACTIVATORS)
•Gemfibrozil
•Fenofibrate
•Ciprofibrate
•Bezafibrate
Drugs of choice for treating
chylomicronaemia, hyperlipidaemia with type
III hyperlipoproteinemia, severe
hypertriglyceridemia (triglycerides > 1000
mg/dL)

16. MECHANISM
bind to the PPARα and increase expression of
lipoprotein lipases, results in:
•↓ VLDL and IDL
•Modest ↓ LDL
•↑ HDL in most patients

17. SIDE EFFECTS
•Gallstones (increase in cholesterol content of
bile)
•Myositis
•GI side effects occur in up to 5% of patients
•Should not be used by children or pregnant
women
•Renal failure and hepatic dysfunction are
relative contraindications to the use of fibrates

18. CHOLESTEROL ABSORPTION
INHIBITOR
Ezetimibe
NPC1L1× Clathrin AP2
(Enterocytes-endocytosis)
Monotherapy in patients with ↑ LDL-C who
are statin intolerant
Combination with statin ⇒ additive
reductions in LDL-C

19. •Mechanism: prevents intestinal absorption of
cholesterol by blocking transporter NPC1L1,
results in ↓ LDL
•Bile-acid sequestrants inhibit absorption of
ezetimibe; avoid concurrent use
•Combination products containing ezetimibe
and a statin should not be used by women in
childbearing years in the absence of
contraception
•Well tolerated agent
•Side effect: gastrointestinal distress

20. PCSK9 INHIBITORS
(PROPROTEIN CONVERTASE
SUBTILISIN/KEXIN TYPE 9 )
•Alirocumab
•Evolocumab
•Protease that binds to the LDL receptor on the
surface of hepatocytes and enhances lysosomal
degradation of the LDL receptor, resulting in
higher plasma LDL concentrations
Adjunct to diet and maximally tolerated
statin therapy for adults with hoFH,
heFH or clinical ASCVD who require
additional lowering of LDL-C

21. •Hypersensitivity or injection site reactions are
possible
•Most effective agents at reducing LDL-C
•Like other monoclonal antibodies, influenza-
like symptoms, nasopharyngitis, upper
respiratory infections may occur
•Used in addition to maximally tolerated statin
doses

22. INHIBITOR OF APO B-100
SYNTHESIS
Mipomersen
•Used as an adjunct to lipid lowering agents and
diet in patients with hoFH
•Adverse effects include injection site reactions,
flu-like symptoms, headache, and elevation of
liver enzymes

23. INHIBITOR OF LIVER
MICROSOMAL TRIGLYCERIDE
TRANSFER PROTEIN
Lomitapide
•Used as an adjunct to diet for lowering LDL-C,
total cholesterol, apo B, and non–HDL-C in
patients with hoFH
•Adverse effects include GI symptoms, elevation
of serum liver enzymes, and increased liver fat
in most patients

24. THANK YOU