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Lipitor Atorvastatin

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Lipitor (Atorvastatin) Team E: Jenna Hargens. Michael Harrington. Nick Herga. Ashley Holt ... Increased expression of LDL receptors on liver cells ... – PowerPoint PPT presentation

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Title: Lipitor Atorvastatin


1
Lipitor (Atorvastatin)
Team E Jenna Hargens Michael Harrington Nick
Herga Ashley Holt Robert Hutchins Meagan
Jarrell
2
Marketing
3
Chemical Structure
4
Cholesterol Biosynthesis
5
Mechanism
  • competitive inhibitor of HMG-CoA reductase

Part of cholesterol synthesis pathway
Mevalonate
3-hydroxy-3-methylglutaryl-CoA
(HMG-CoA)
6
Mechanism
  • Decrease in cholesterol synthesis
  • Increased expression of LDL receptors
    on liver cells
  • Increased LDL cholesterol uptake by liver
    cells
  • Reduces amount of cholesterol in blood
  • WHY IS HIGH CHOLESTEROL IN THE BLOOD BAD?

7
Function
  • High cholesterol
  • Atherosclerosis
  • Cardiovascular disease, strokes, heart attacks

8
Atherosclerosis
9
Active Site Model
  • pharmacophore of atorvastatin hydrogen bonds with
    Ser684, Asp690, Lys691, Lys692, Glu559 (red)
  • fluorophenyl ring of atorvastatin forms polar
    interactions with Arg590 (yellow)
  • Oxygen associated with amide also forms hydrogen
    bonds with Ser565(purple)

10
Method of Administration
  • 10, 20, 40, and 80 mg tablets for oral
    administration
  • A patients response to their first few
    treatments can lead to a change in the dosage

11
Physical Properties
  • White to off-white crystalline powder
  • Solubility
  • Insoluble in aqueous solution with pH
  • Slightly soluble in distilled water and
    acetonitrile
  • Soluble in methanol
  • Molecular Weight 1209.42 g/mol
  • (C33H34FN2O5)2Ca23H20

12
Metabolism
  • Log P 4.1
  • Due to hydrophobic character, absorbed quickly
    after oral administration
  • Low systemic availability
  • clearance in GI mucosa
  • Hepatic first-pass metabolism
  • Liver is the primary site of action

13
Distribution
  • Membrane consists of lipid bilayer
  • Hydrophilic statins cannot penetrate without a
    protein
  • Hydrophobic statins can diffuse across
    phospholipid bilayer
  • Hydrophobic statins can enter extra-hepatic and
    hepatic cells
  • Protein binding of atorvastatin is usually in the
    98 range

14
Excretion
  • Eliminated primarily in bile following hepatic
    metabolism
  • Only 2 recovered in urine after oral
    administration

15
Minor Side Effects
  • Diarrhea
  • Headache
  • Constipation/gas
  • Rash
  • Upset stomach and/or stomach pain
  • Muscle and joint pain

16
Serious Side Effects
  • muscle problems
  • kidney problems/failure
  • liver problems
  • Breastfeeding mothers should not take Lipitor
    because of the transmission to the baby through
    the mothers milk

17
Conclusion
  • Pfizer reported 12.6 billion in sales in 2006
    from Lipitor alone
  • Even though it is very effective in treating high
    cholesterol, many physicians are switching
    patients to other statins that are cheaper
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