Organic Chemistry II 202 - DDB - 05 CAM Aranesp By Matthew Seidler (0588687) Winter 2007 John Abbott...
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Transcript of Organic Chemistry II 202 - DDB - 05 CAM Aranesp By Matthew Seidler (0588687) Winter 2007 John Abbott...
Organic Chemistry II 202 - DDB - 05
CAM
Aranesp
By Matthew Seidler (0588687)
Winter 2007
John Abbott College
Overview
• Introduction• What is it?• History• Structure/Chemistry
• Benefits/Risks
• Competitors
• Personal Thoughts
Red Blood Cells
• Transport oxygen to various parts of the body
• Oxygen = NP, Blood = P
• Need a way to transport oxygen
• Divide rapidly
• When your body makes fewer RBCs, anemia develops
What exactly is Aranesp?• Darbepoetin alfa is a synthetic form of
erythropoietin• Erythropoietin = produced by kidney,
hormone that stimulates RBC production• Stimulates erythropoiesis (process by which
erythrocytes (RBCs) are produced when oxygen is low (hypoxia)
• Stimulates bone marrow to produce RBCs
• When is oxygen supply lowered?• Exercise• High altitudes, etc
How EPO works
• EPO binds to receptors (EpoR) in bone marrow to speed up mitosis of cells responsible for making RBCs
• Oxygen in blood rises, EPO production slows down
EPO
Amgen, Inc.
• International Biotech company in California
• The largest independent biotech firm, 15K staff members
• As of 09/06, Amgen had eight FDA approved drugs (one of which was Aranesp)
Back to the drug…
• 09/01: approved by FDA for treatment in anemia in patients with chronic renal failure • Kidneys secrete erythropoetin, which stimulates RBC
production• Patients w/ renal failure commonly suffer from anemia (lower
RBC count)• 06/01: approved by European Medicines Agency for the same
treatments, but also for anemia patients undergoing chemotherapy• Chemotherapy affects rapidly dividing cells (I.e. RBCs)
• You therefore need more erythropoetin in order to stimulate RBC production
Another Use
• Patients who require a blood transfusion or have surgery where blood loss is expected, EPO is given in advance
• If blood is lost in surgery…
How is it made?
• Produced by recombinant DNA technology in modified Chinese hamster ovary cells
• Differs from real erythropoietin (EPO) in that it has two more N-linked oligosaccharide chains
• Why not just use real EPO?
Chemistry of the drug
• C815H1317N233O241S5
• Ok, let’s draw it. IHD = 1/2(2*815+2…)
• Molar mass = 18396.1 g/mol
Anemic Cancer Patients
• 01/07, Amgen wrote a letter that highlighted the results from a recent anemia of cancer trial, and warned doctors
• They informed the FDA that control over the cancer was worse in patients on Aranesp (against those who weren’t on the drug)
What did the FDA say?
• Released a public health advisory, in March 07, and a clinical alert for doctors about the use of erythropoeisis-stimulating agents such as epogen and darbepoeitin
• Use caution when using these drugs in cancer patients
• Lack of clinical evidence to support improvements in these situations
Risks• Increases the risk of…
• Cardiovascular problems (RBCs increases viscocity of blood)
• Strokes• Hypertension• Congestive heart failure• Myocardial infarction (heart attack)• Hypertension
• Seizures (why?)• Vascular thrombosis (clot inside blood vessel)• Edema (fluid collecting in cavities of body) (why?)• Side effects = fever, chest pains, nausea, etc
$10 000/ yr for drug (dialysis patient)
$12 000/ yr for drug (chemo patient)
Sales: $10 B in 2004
Abuse
• Cross country skiers Larisa Lazutina & Olga Danilova of Russia and Johann Muhlegg of Spain
EPO as a blood doping agent
• Used by healthy athletes to give a competitive advantage
• Increases oxygen carrying capacity of the blood
• Therefore, increases aerobic respiratory capacity of the muscles
• Helps make more ATP
Continued
• Useful for bicycle races (offsets decrease in RBC count that occurs over several races)
• What happens if you OD?• The drug can produce so many RBCs that
the blood thickens and strains the heart (I.e. during sleep when HR is low)
Competitors
• From Amgen: Epogen & Aranesp (Brand names)
• There’s also Dynepo
Dynepo
• Pharmaceutical EPO under development by Shire Pharmaceuticals
• Launched in Europe in 2006• Amgen patents prevent it from
launching here• Instead of being made from cultured
animal cells, it’s made from cultured human cells
Dynepo
• Has a true form of sialic acid & oligosaccharide residues
• This makes it longer lasting than Amgen’s products (this is not confirmed yet…)
• Undetectible in urine tests for EPO that is used on athletes
Personal Thoughts
• Jehova’s Witnesses
• Drug can be used for many things
QUESTIONS?