This document discusses antihyperlipidemic drugs used to treat hyperlipidemia. It begins by defining hyperlipidemia and describing risk factors. It then covers the various classes of lipid-lowering drugs including HMG-CoA reductase inhibitors (statins), bile acid sequestrants, fibrates, nicotinic acid, cholesterol absorption inhibitors, and PCSK9 inhibitors. For each class, it provides examples of drugs, their mechanisms of action, therapeutic uses, and major side effects and drug interactions. The document concludes with recommendations on drug therapy and monitoring treatment effectiveness.

1. Antihyperlipidemic Drugs
Edson Mutandwa MBBS v

2. HYPERLIPIDEMIA
• Hyperlipidemia refers to increased levels of lipids (fats) in the blood,
including cholesterol and triglycerides. (uptodate)
• hyperlipidemia significantly increase your risk of developing
cardiovascular disease, coronary artery disease, cerebrovascular
disease, and peripheral vascular disease.

3. LIPID METABOLISM

4. RISK FACTORS FOR HYPERLIPIDEMIA
• Family history of early heart disease (father before the age of 55 years
and mother before the age of 55 years)
• Cigarette smoking
• High blood pressure
• Age (men older than 45 years and women olderthan 55 years)
• Low HDL levels
• Obesity
• Diabetes
• etc

5. DIAGNOSIS OF HYPERLIPIDEMIA
• Diagnosis is typically based on medical history, physical examination
and blood test done after overnight fasting

6. WHEN TO CHECK LIPID PANEL
Two different Recommendations
 Adult Treatment Panel (ATP III) of the National Cholesterol Education
Program (NCEP)
• Beginning at age 20: obtain a fasting (9 to 12 hour) serum lipid profile consisting of total
cholesterol, LDL, HDL and triglycerides
• Repeat testing every 5 years for acceptable values
 United States Preventative Services Task Force
• Women aged 45 years and older, and men ages 35 years and older undergo screening
with a total and HDL cholesterol every 5 years.
• If total cholesterol > 200 or HDL <40, then a fasting panel should be obtained
• Cholesterol screening should begin at 20 years in patients with a history of multiple
cardiovascular risk factors, diabetes, or family history of either elevated cholesterol
levels or premature cardiovascular disease

7. Management of hyperlipidemia
Management of hyperlipidemia start with therapeutic life changes
(TLC) which includes;
• a cholesterol-lowering diet (TLC diet),
• physical activity,
• quitting smoking (if applicable),
• weight management,
• and antihyperlipidemia drugs

8. Antihyperlipidemic drugs classification
• HMG-CoA reductase inhibitors
• Bile acid sequestrants
• Fibrates
• Nicotinic acid (Niacin)
• cholesterol absorption inhibitors
• PCSK9 inhibitors

9. HMG-CoA reductase inhibitors
 Examples; Lovastatin, atorvastatin, rosuvastatin (5 to 40 mg/day)
 Mechanism of action
• Analogs of HMG (3-hydroxy-3 methylglutaryl-CoA)
• HMG-CoA reductase catalyzes synthesis of mevalonic acid from HMG-CoA and is the
rate limiting step in cholesterol biosynthesis
• Leads to up-regulation of LDL receptors in liver
 Therapeutic Uses
• Great for all hyperlipidemias involving increased levels of LDL or cholesterol
• Atherosclerosis; stroke prevention
• Primary prevention of CAD

10. Major side effect and drug interactions
Side effects
• Headache
• nausea
• sleep disturbance
• elevations in hepatocellular enzymes and alkaline phosphatase. CI in hepatic
dysfunction
• Myositis and rhabdomyolysis, primarily when given with gemfibrozil or
cyclosporine; myositis is also seen with severe renal insufficiency (CrCl <30
mL/min).
• CI in pregnancy
Drug interactions; Lovastatin, atorvastatin, rosuvastatin, and simvastatin potentiate
effect of warfarin; this interaction is not seen with pravastatin, fluvastatin, or
pitavastatin. Most statins can also affect digoxin metabolism and levels

11. Bile acid sequestrants
 Examples; Cholestyramine (4 to 24 g/day), Colestipol (5 to 30 g/day),
Colesevelam (3.75 g/day)
 Mechanism of action
• Anion-exchange resin – binds bile acids in intestinal lumen preventing
enterohepatic circulation (this increases excretion of bile which is
made from cholesterol),this causes an up-regulation of hepatic LDL
receptors and increased production of cholesterol
 Therapeutic Uses
• Uses Hyperlipidemias involving ISOLATED INCREASES OF LDL

12. Major side effect and drug interactions
Side effects
• Constipation
• Flatulence
• Dyspepsia
• Hypertriglyceridemia
• Hyperchloremic acidosis (since they exchange Cl)
• Bind many things (drugs, vitamins, toxins, anything fat soluble) which limits their
absorption
• Prexisting coagulopathy is a contraindication since they prevent absorption of vit K
• Drug interactions Impaired absorption of fat soluble vitamins and co-administered
medications including: Amiodarone, digoxin, warfarin, thiazides, β-blockers,
levothyroxine, others; interaction can be minimized by taking other medications at least
1 hour before or 4 hours after bile acid sequestrant.

13. Fibrates
• Examples; Gemfibrozil (600 mg BID), Fenofibrate (Nanocrystal 145 mg/day
Micronized 160 to 200 mg/day0
 Mechanism of action
• activation of nuclear transcription receptor to increase LPL synthesis
(removes TGs from lipoproteins); enhanced removal of VLDL from plasma
 Theurapitic use
• DOC fro type III lipoproteinemia (familial dysbetalipoproteinemia)
• Hypertriglyceridemias
• useful for Pruritus in biliary obstruction (↑ bile acids)

14. Major side effect and drug interactions
• Side effects
• Skin rash,
• gastrointestinal (nausea, bloating, cramping)
• myalgia;
• lowers blood cyclosporine levels; potentially nephrotoxic in
cyclosporine treated patients. Avoid in patients with CrCl <30 mL/min.
(Fenofibrate)
• Potentiates warfarin action. Absorption of gemfibrozil diminished by
bile acid sequestrants. (Gemfibrozil)

15. Nicotinic acid (Niacin)
 Examples; Niacin (IR: 1 to 6 g/day or XR 0.5 to 2 g/day)
 Mechanism of action
• It is a potent inhibitor of lipolysis in adipose tissues which decreases
mobilization of FFAs (major precursor of TGs) to the liver which in turn
decreases VLDL (after few hours)
• Increases HDL levels
 Theraupetic use
• Uses Hyperlipidemias with very high VLDL and LDL
• Patients with very low HDL

16. Major side effect and drug interactions
Side effects
• dry skin
• myositis
• Prostaglandin-mediated cutaneous flushing, warm sensation
• Headache
• Pruritus, Nausea, Vomiting, diarrhea
• hyperpigmentation (particularly in intertriginous regions); acanthosis nigricans;
• Decreased glucose tolerance
• Hepatotoxicity (check AST, ALT levels)
• Rhabdomyolysis
• Hyperuricemia (inhibits tubular secretion of uric acid)

17. Cholesterol absorption inhibitors
 Examples; Ezetimibe (10 mg/day)
 Mechanism of action
• Localizes at the brush border, selectively inhibits intestinal absorption
of cholesterol and related sterols (only blocks exogenous sterol
intake)
 Therapeutic use
• Used in hypercholesterolemia together with statins & diet regulation

18. Major side effect and drug interactions
Side effects
• Diarrhea
• Abdominal pain
• CI liver dysfunction

19. PCSK9 inhibitors
• Examples; Alirocumab (75 to 150 mg 2/7 w), Evolocumab (140 mg 2/7
w or 420 mg 1/12 m)
• Proprotein convertase subtilisin kexin 9 (PCSK9) is a serine protease
produced predominantly in the liver that leads to the degradation of
hepatocyte LDL receptors and increased LDL-C levels
• This category of lipid lowering therapy appears promising in a range
of clinical situations.
• They are given subcutaneously
• The major side effect is injectin site reaction

20. DRUG THERAPY
• If no improvement within 6 weeks with a single drug therapy, the
dose should be increased. If no improvement after 3 months change
the drug or consider combination therapy:
• Bile acid resins can be safely combined with statins or nicotinic acid
(↓ LDL, VLDL cholesterol levels respectively).
• Ezetimibe + statins → synergistic effects.
• Fibrates and statins are CI because of myopathy.
• Nicotinic acid and statins (must be cautiously used) because of
myopathy.

21. EFFECTS OF ANTIHYPERLIPIDEMIC DRUGS

22. REFERENCES
• http://www.mayoclinic.org/diseases-conditions/high-blood-
cholesterol/in-depth/cholesterol-medications/art-20050958
• Uptodate; Treatment of lipids (including hypercholesterolemia) in
secondary prevention; Robert S Rosenson, MD, This topic last
updated: Sep 11, 2015

23. Thank you