CHEMISTRY PROJECT Drugs

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CHEMISTRY PROJECTDrugs Aspirin
cis-PlatinGROUP 5
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GROUP MEMBERS

• Leader Agnes Cheung (7)
• Members Clara Cheung (6)
• Jessica Luk (24)
• Charmaine Tang (30)
• Erin Wong (33)

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CONTENT

• Structure , historical development and discovery
  of aspirin
• Structure , historical development and discovery
  of cis-platin
• Key stages of drug development

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Structure, Historical Development and Discovery
of Aspirin
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WHAT IS ASPIRIN?

• Known as acetylsalicylic acid
• A salicylate drug
• as an analgesic to relieve minor aches and pains
• as an antipyretic to reduce fever
• as an anti-inflammatory medication

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THE USES OF ASPIRIN

• To relieve
• Pain
• Fever
• Headache
• To prevent
• Heart attacks and strokes
• Blindness and kidney damage associated with
  diabetes

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HISTORY AND DEVELOPMENT OF ASPIRIN

• Salicin, has been used as a pain reliever
  (analgesic) for centuries.
• In the middle of the last century it was found
  that salicin is a glycoside formed from a
  molecule of salicylic acid and a sugar molecule.
• Unfortunately, salicylic acid attacks the mucous
  membranes of the mouth and esophagus and causes
  gastric pain.

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HISTORY AND DEVELOPMENT OF ASPIRIN

• In 1893,Felix Hoffman, a chemist for Friedrich
  Bayer reasoned that the corrosive nature of
  salicylic acid could be altered by addition of an
  acetyl group
• In 1897, scientists at Bayer began investigating
  acetylsalicylic acid as a less-irritating
  replacement
• dubbed this drug Aspirin and was selling it
  around the world in 1899

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STRUCTURE OF ASPIRIN
-IUPAC name 2 - acetoxybenzoic acid
Chemical Formula C6H4(OCOCH3)CO2H
- Also know as Acetylsalicylic acid (ASA)
Can you identify the functional groups of aspirin?
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SIDE EFFECTS OF ASPIRIN

• Nausea and vomiting problem
• solution antiemetic drugs (???)
• Heartburn
• solution dosage recommendation
• Stomach irritation
• solution enteric-coated
• Indigestion

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Structure, Historical Development and Discovery
of cis-Platin
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WHAT IS CIS-PLATIN?

• Platinum-based chemotherapy drug
• to treat various types of cancers, including
  sarcomas, some carcinomas (e.g. small cell lung
  cancer, and ovarian cancer), lymphomas, and germ
  cell tumors
• first member of a class of anti-cancer drugs

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THE USES OF CIS-PLATIN

• Anticancer Agent
• Inhibiting cell division
• Altering the DNA of the cancer
• Reducing the size of tumours

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DISCOVERY AND DEVELOPMENT OF CIS-PLATIN

• In 1965, Barnett Rosenberg discovered that
  electrolysis of a platinum electrode produced
  cisplatin, which inhibited binary fission in
  Escherichia coli (E. coli) bacteria
• unable to divide while cell growth remained
  normal causing the bacteria to grow 300 times
  its normal length
• Rosenberg then conducted a series of experiments
  to test the effects of various platinum
  coordination complexes on human leukemias cells
  (L1210) and on sarcomas artificially implanted in
  rats
• cis-PtCl2(NH3)2 was the most effective out of
  this group, which started the medicinal career of
  cisplatin
• Approved for clinical use by the United States
  Food and Drug Administration (FDA) in 1978

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STRUCTURE OF CIS-PLATIN

• Formal name cis-diamminedichloroplatinum (II),
• abbreviated to cis-DDP
• Exists as an electroneutral, four coordinate
  platinum complex

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Side Effects of cis-Platin

• Kidney Damage
• solution aggressive diuresis (????)
• Nausea and vomiting problem
• solution antiemetic drugs (???)
• Blood test abnormalities
• E.g. low Mg, Ca, K, blood counts, red and white
  blood cell

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KEY STAGES OF DRUG DEVELOPMENT
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KEY STAGES OF DRUG DEVELOPMENT

• Lead compound discovery
• 2) Molecular modification
• 3) Formulation development
• 4) Safety tests and human trials
• 5) Approval for marketing

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LEAD COMPOUND DISCOVERY

• Lead compound
• A compound with desired biological activity
• Can be modified to another compound without
  unwanted side effects
• Usually involve screening and testing of more
  than thousands of compounds
• Assisted with Computer programs

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MOLECULAR MODIFICATION

• For Aspirin
• Lead Compound lining of mouth
• oesophagus
• stomach
• Modify the molecular structure of lead compound
  to improve performance

Harmful
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FORMULATION DEVELOPMENT

• Different types of formulation tablets, capsule
  , liquid or intravenous fluid
• Find out which formulation of the drug brings the
  greatest effect and is the mist suitable to the
  patients
• For Aspirin tablets
• For Cis-platin liquid

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SAFETY TESTS AND HUMAN TRIALS

• Preclinical Trial
• Testing on animals or living tissues on Petri
  dish
• Mainly safety testing
• Eg. absorption and the toxicity of the drug's
  metabolites, and the speed with which the drug
  and its metabolites excreted from the body, etc.
• Clinical Trial
• Phase 1
• - Usually involve testing on healthy people
• - Under 100 volunteers
• - Mainly safety, e.g. to see the toxicity,
  short- term side effects, dose escalation of the
  drug, etc.
• - Several months

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SAFETY TESTS AND HUMAN TRIALS

• Phase 2
• Involve testing on patients
• Several hundreds patients
• Mainly to test the effectiveness of the drugs
• Several months to 2 years
• Phase 3
• - Testing on general population (several hundreds
  to several
• thousands of people )
• - Both the patients and healthy people
• - Testing the safety and effectiveness
• - Focusing more on the long- term side effects
• - Preparations are made for submitting the BLA or
  NDA
• - 1 to 4 years

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SAFETY TESTS AND HUMAN TRIALS
Phase Kind of people No. of people Length Testing on
1 Healthy 100 Months Safety
2 Patients Hundreds Months to 2 years Effectiveness
3 Both Thousands 1-4 years Both
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APPROVAL FOR MARKETING

• Pharmaceutical company makes a formal application
  to the regulatory authority
• Material needed
• Results and analysis from drug tests on animals
  and humans
• A description of manufacture of the drug
• Judging criteria
• Safety and effectiveness of the drug
• Whether its benefits outweigh its risks
• Whether its labelling info. are appropriate
• Whether the manufacturing methods are adequate
  for ensuring purity and integrity of drug

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APPROVAL FOR MARKETING

• Phase 4 clinical research is done after the drug
  is approved for marketing
• To know more about
• the drugs
• Side effects
• Safety
• Long-term risks
• Benefits

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REFERENCE

• http//en.wikipedia.org/wiki/Aspirin
• http//en.wikipedia.org/wiki/Cis-platin
• New Way Chemistry Book 3B

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THE END