Your SlideShare is downloading. ×
Hypolipidemic agents
Upcoming SlideShare
Loading in...5
×

Thanks for flagging this SlideShare!

Oops! An error has occurred.

×

Saving this for later?

Get the SlideShare app to save on your phone or tablet. Read anywhere, anytime - even offline.

Text the download link to your phone

Standard text messaging rates apply

Hypolipidemic agents

6,908
views

Published on

This is a wonderful presentation on hypolipidemic drugs by Dr.Sachin Kuchya. …

This is a wonderful presentation on hypolipidemic drugs by Dr.Sachin Kuchya.
Kudos for him.


1 Comment
2 Likes
Statistics
Notes
No Downloads
Views
Total Views
6,908
On Slideshare
0
From Embeds
0
Number of Embeds
1
Actions
Shares
0
Downloads
391
Comments
1
Likes
2
Embeds 0
No embeds

Report content
Flagged as inappropriate Flag as inappropriate
Flag as inappropriate

Select your reason for flagging this presentation as inappropriate.

Cancel
No notes for slide

Transcript

  • 1. Hypolipidemic Agents Sachin Kuchya, MD Assistant Professor, Department of Pharmacology NSCB Medical College, Jabalpur
  • 2. Why do we need them?
    • Low HDL & elevated LDL-c are known risk factor for CHD.
    • Elevated TG’s are known to cause Pancreatitis.
    • In well controlled clinical trials ,fatal & nonfatal CHD events & strokes was reduced by as much as 30-40% as per Scandinavian Simvastatin Survival Study.
  • 3. Overview of Presentation
    • Physiology
    • Pharmacological targets
    • Drugs
    • Clinical states
    • Special populations
    • Combination Drug Regimens
  • 4. GLOSSARY
    • Lipid – water insoluble compounds, comprising of FFA, TG, CHL, CHL- esters.
    • LIPOPROTEIN - complex of lipids + apoproteins
    • Chylomicrons – largest of lipoproteins, carry TG & CHL- esters from the gut to other tissues
    • VLDL - very low density lipoprotein, principal form secreted by liver, represents triglyceride content in lipid profile.
    • LDL - low density lipoprotein, derived from VLDL, represents CHL.
    • HDL - high density lipoprotein, extracts CHL from body tissues.
    • Lp(a)- LDL + apoprotein a, is known to be atherogenic .
    • CETP - Cholesteryl Ester Transfer Protein .
  • 5. PHYSIOLOGY Enterohepatic circulation - Bile acids CHL Pool Dietary CHL De novo CHL synthesis HMG CoA reductase enz. VLDL Chylomicrons 50% 50% VLDL LDL TG CHL
    • Adipose tissue (Storage)
    • Skeletal M
    • Cardiac M
    • Breast tissue during lactation
    To various body tissues, Gut HDL2 HDL3 CHL ester TG LDL CETP Tightly regulated Diurnal variation
  • 6.
    • Dietary restriction
    • Cholesterol absorption inhibitor
    • Bile acid binding resin
    • HMG CoA reductase inhibitor
    • VLDL secretion inhibitor
    • Fibric acid derivatives
    • CETP inhibitor
    Non Pharmacological & Pharmacological targets 1 2 3 4 5 6 7 Dietary Atheroma HDL2 CHL Pool CHL VLDL Chylomicrons 50% 50% VLDL LDL TG CHL Gut HDL3 CHL ester TG LDL CETP Bile acids
  • 7. Statins – effect on lipids
    • LDL-c
    • Lowers LDL-c by 20-50%
    • TG
    • If >250 mg/dl, then significant reduction is seen.
    • HDL-c
    • Increases HDL levels by 5- 10%.
    • Lp(a)
    • No effect is seen .
  • 8. Statins – additional effects
    • Improved endothelial function
    • Prevents weakening & rupture of atherosclerotic plaque.
    • Reduces platelet aggregation.
    • Lowers C- Reactive protein levels – anti-inflammatory action.
  • 9. Statins – Clinical Pharmacokinetics
    • Should be administered orally
    • Lo – sim – pra – fluvastatin, should be administered in evening / with dinner.
    • Ator – Rosuvastatin, can be given at any time of day.
    • All statins will need dose adjustments with gemfibrozil, cholestyramine, niacin.
    • Role of CYP3A4 & CYP2C9 enz.
  • 10. Statins – adverse effects
    • Major side effects
      • Myopathy (Diabetes, Advancing age & Drug)
      • Hepatotoxicity
      • Teratogenicity (Lo - Fluvastatin).
    • Minor
      • Dyspepsia
      • Generalized eczematous rash (Simvastatin)
  • 11. Statins – indications
    • Effective in almost all patients with elevated LDC-c levels
    • Exception – familial homozygous hypercholesterolemia .
  • 12. Bile acid binding resins
    • LDL-c
    • Lowers LDL-c by 12 –28 %.
    • TG
    • May increase transiently .
    • HDL-c
    • Increases HDL levels by 4 –5%.
  • 13. Bile acid binding resins – adverse effects
    • No systemic absorption, no systemic toxicity.
    • Only local GI side effects
    • Bloating
    • Dyspepsia
    • Constipation
  • 14. Bile acid binding resins
    • Indications – safest ,
    • Hypolipidemic of choice during pregnancy.
    • As a second line agent, if elevated LDL-c is not adequately controlled with statins .
    • Drug interactions –
    • Inhibits GI absorption of thiazides, furosemide, thyroxine, statins, ezetimibe, fibrates, warfarin etc.
    • Any additional drug should be administered 1 hr before or 4 hrs after the resins.
  • 15. Ezetimibe
    • Lowers LDL-c by 15- 20%.
    • (should be combined with a statin)
    • Increases HDL levels by 1- 2%.
    • Lowers TG’s by 5%.
  • 16. Ezetimibe
    • Adverse effects – almost none, well tolerated.
    • No enzyme induction /inhibition is seen.
    • Precaution : should not be simultaneously administered with bile acid binding resins.
  • 17. Niacin
    • LDL-c
    • Lowers LDL-c by 20- 30%
    • TG
    • Lowers TG levels by 35-45%
    • HDL-c
    • Increases HDL levels by 30- 40%.
    • Lp(a)
    • Lowers Lp(a) level by 40%.
    Physiologic dose, as vitamin B3– 50mg/ day Pharmacologic dose, as hypolipidemic agent – 2 – 6gm/day.
  • 18. Niacin
    • Adverse effects
        • Cutaneous flushing
        • Dry skin, itching
        • Gastritis
        • Hepatitis
        • Precipitation of acute gout
        • Hyperglycemia
    • Contraindications
    • H/o of gastric ulcer, gout, diabetes milletus
  • 19. Niacin - indications
    • Hypertriglyceridemia
    • Elevated LDL-c,
    • Especially in those with low HDL-c levels.
  • 20. Fibric acid derivatives
    • LDL-c
    • Increases LDL-c by upto 10-30%.
    • TG
    • Lowers TG’s by upto 50%
    • HDL-c
    • Increases HDL levels by 15%.
  • 21. Fibric acid derivatives
    • Adverse effects
      • Gallstone (Clofibrate)
      • Dyspepsia & abdominal pain
      • Increased risk of myopathy (gemfibrozil + statins)
    • Contraindications
      • Hepatic & renal dysfunction
  • 22. Fibric acid - indications
    • Hypertriglyceridemia
    • Chylomicronemia
    • Type III dysbetalipoproteinemia
  • 23. CETP inhibitor - Torcetrapib
    • Increases HDL levels by 45- 100%.
    • Under clinical trial.
  • 24. ω3 – fatty acids
    • EPA & DHA, found primarily in fish oils, when given in high doses upto 6 gm/day, result in inhibition of VLDL secretion.
    • TG level falls upto 75%
    • Are very useful in treatment of severe hypertriglyceridemia’s ( > 1000mg/dl).
    • However, these often raise LDL-c levels , in a manner similar to that seen with fibric acid derivatives, the clinical impact is however unclear.
    • Commonest side effect is belching with a fishy odour
  • 25. Clinical states
    • In this section, we will have some clinical states.
    • This exercise shall rationalize the use of hypolipidemic agents.
  • 26. Chylomicronemia Dietary restriction 1 Clinical state - 1 CHL Pool Dietary CHL VLDL Chylomicrons 50% 50% VLDL LDL TG CHL To various body tissues, Gut HDL2 HDL3 CHL ester TG LDL CETP 1 Bile acids
  • 27. Hypercholesterolemia 2 5 4 3 Cholesterol absorption inhibitor Bile acid binding resin HMG CoA reductase inhibitor VLDL secretion inhibitor Clinical state - 2 CHL Pool Dietary CHL De novo CHL synthesis HMG CoA reductase enz. VLDL Chylomicrons 50% 50% VLDL LDL TG CHL To various body tissues, Gut HDL2 HDL3 CHL ester TG LDL CETP 2 5 3 4 Bile acids
  • 28. CHL Pool Dietary CHL VLDL Chylomicrons 50% 50% VLDL LDL TG CHL atheroma Gut HDL2 HDL3 CHL ester TG LDL CETP 6 5 Hypertriglyceridemia 6 5 VLDL secretion inhibitor Fibric acid derivatives Clinical state - 3
  • 29. Low HDL-c levels VLDL secretion inhibitor CETP inhibitor 5 7 Clinical state - 4 CHL Pool Dietary CHL VLDL Chylomicrons 50% 50% VLDL LDL TG CHL Atheroma Gut HDL2 HDL3 CHL ester TG LDL CETP 7 5
  • 30. Special Population
    • Children
    • Women – Adolescence / Pregnancy/ Lactation/ Postmenopausal.
  • 31. Special population – Children
    • Less than 2 yrs of age – no dietary restriction & no drug therapy.
    • > 2yrs – 10yrs – Dietary restriction of saturated and total fats ; CHL restricted diet only.
    • 10 yrs & above – Diet therapy
    • Drug therapy is indicated only after an adequate trial of dietary control for 6mo – 1 yr.
  • 32. Special population – Children
    • Drugs
      • Bile acid sequestrants (resins) are the first line agents of choice.
    • If not - tolerated then,
      • Statins can be given,
      • Ator – lova – sim, approved for 11yrs & above.
      • Pravastatin, for 8 yrs & above .
  • 33. Women
    • Statins should be used with caution in adolescent girls / females, likely to conceive.
    • Bile acid binding resins are the only CHL – lowering drugs used during pregnancy .
    • In post menopausal women, who wish to have HRT, elevated TG’s if any should be controlled with Dietary restriction, weight control and fibrates/ statins + fibrates, prior to initiation of HRT.
  • 34. Combination regimens – why?
    • Maximize reduction of LDL & VLDL.
    • Minimize side effects by using smaller doses of drugs.
    • Allow use of resins, patients with elevated TG’s & LDL.
    • Treat increased LDL, found consequent to treatment of elevated TG with fibric acid derivatives.
  • 35. Combination regimens – when?
    • After diet & a single drug have been found insufficient.
    • Statins, being the most effective & well tolerated, should be the first drug.
    • Effect on Plasma lipoprotein levels & side effects should be assesed only after 4 –8 weeks of therapy.
  • 36. LDL-c reduction
    • Statin + Fenofibrate
    • Statin + Niacin
    • Statin + Resins
  • 37. VLDL reduction
    • Nicotinic acid + fibric acid
    • Addition of fish oils, may be helpful.
  • 38. Minimize doses and side effects
    • Statin + Ezetimibe is the safest combination.
  • 39. Diabetic patient
    • The defect,
    • Elevated TG’s / LDL
    • Low HDL-c
    • Glycosylated LDL
    • The treatment,
    • Adequate glycemic control & dietary restrictions.
    • Drugs
  • 40. Diabetic patient - drugs
    • Niacin – impairs glycemic control
    • Resins – increases TG
    • Fibric acid level – increases LDL
    • So, combination of hypolipidemics is must,
    • Statin + fenofibrate, is the ideal combination .
  • 41. Thank you Topic is open for queries