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Pharmaceutical Products

Pharmaceutical Products. Alters incoming sensory sensations Alters mood or emotions Alters physiological state-consciousness, activity level, or coordination Assist healing-------placebo effect. So ya want a new drug. Identify the need…will you make money Structure Synthesis

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Pharmaceutical Products

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  1. Pharmaceutical Products • Alters incoming sensory sensations • Alters mood or emotions • Alters physiological state-consciousness, activity level, or coordination • Assist healing-------placebo effect

  2. So ya want a new drug • Identify the need…will you make money • Structure • Synthesis • Yield and extraction

  3. Determine lethal dose • LD50 • Amount required to kill 50%of the population • Determine effective dose • We need a noticeable effect in 50% of the population -ED50 • Therapeutic index • LD50 / ED50 or ToxicDose50/ED50cuz killing humans is wrong • Therapeutic window • Range of dosages between the minimum amounts of the drug that produce the desired effect an a medically unacceptable adverse effect

  4. Clinical trials • Half of the population receives the drug/half of the population receives a placebo • Play close attention to safety and side effects • Can occur in three phases with the group of individuals increases with each phase.

  5. Side effects • Car accident victim • Receives morphine for pain • Side effect is constipation • Aspirin – fever reducer / causes bleeding of the stomach

  6. Risk : Benefit • Fen-Phen • Weight lose • Heart valve disease • OxyContin • Pain management • Addiction. . . . . . . . . . . .

  7. Tolerance levels • Body adapts to the action of the drug • As dose increases so does the danger of addiction and reaching LD50 • More studies are done • Prescription / over the counter • Ten years later –drugo is his nameo

  8. How do you like your drugs?

  9. Bioavailability • Fraction of the dosage that reaches the target part of the human • Oral meds depends strongly on the solubility in water • Presence of polar groups (OH, COOH, NH2) • Allows for transport through the intestinal tract and blood plasma

  10. Drug-receptor interactions Turns processes on/off. Stops messaging

  11. Antacids • Neutralize HCl • Aluminum hydroxide • Side effect constipation • Interferes with absorption of phosphates • Bone damage • Sodium hydrogen carbonate • Side effect carbon dioxide gas • bloating belching • Magnesium oxide and magnesium hydroxide

  12. H2-receptor antagonist • Ranitidine or Zantac • Inhibits the production of acid • Binds to histamine H2-receptor • Stops the normal chemical messenger from turning on the acid production

  13. Proton pump inhibitor • Omeprazole (Prilosec) and esomeprazole (Nexium) • Weak base that travels through the cell membrane becomes acidic from the H+ being produced • Binds to pump

  14. Active metabolites • Active form of drugs after they have been processed in the body • Aspirin is salicylic acid • Salicylic acid causes severe stomach irritation • Aspirin is taken in ester form and covert to acid form

  15. Mild Analgesics • Used for pain management • Mild pain • Aspirin

  16. Aspirin • Prevents the production of prostaglandin synthase • Anti-inflammatory NSAID • Prophylactic - prevents bad stuff • Anticoagulant • May prevent certain cancers • Causes bleeding in the lining of the stomach • Causes Reye’s syndrome

  17. Mild Analgesics • Paracetamol-UK • Acetaminophen - US • Maybe safer for kids • Rarely causes kidney damage or blood disorders • Overdose • Brain, liver, and kidney damage

  18. Purification of aspirin • Unreacted salicylic acid is recrystallized • Dissolved in hot solvent • Vacuum filtered • Cooled • Forms crystals because it is close to its saturation point

  19. Determining purity • Melting point • 138 – 140 C • Infrared spectroscopy • Shows functional groups present

  20. Increasing aspirin bioavailability • Form the sodium salt • Increases water solubility

  21. Fluoxetine to ionic salt

  22. Synergistic effect of ethanol • Increase the risk of stomach bleeding when mixed with aspirin • Increases the sedation effective of sedatives

  23. Strong analgesics • Opiates • Temporarily binds to the receptor sites in the brain • Preventing transmission of pain impulses without depressing the central nervous system • Found in the opium poppies • Morphine • Codeine

  24. Codeine OH- is replaced with a –OCH3 morphine Heroin produced by a diesterification reaction. Less polar than morphine-crosses the blood/brain barrier better Semi synthetic

  25. Short term effect • Euphoria • Pain killer • Depresses nervous system • Slows breathing and heart rate • Depresses coughing • Constipation

  26. Long term effects • Loss of sex drive • Disrupts menstrual cycle • Social • HIV • Hepatitis

  27. Testing for ethanol • Breathalyser • Uses Cr2O72- / H+ to oxidize • C2H5OH ethanal ethanoic acid • Gas liquid chromatography • Blood or urine sample is needed • Intoximeters • C-H bonds absorb infrared radiation at -3.30 micrometers • Suspects breath is compared to a clean sample • The intensities of the two emerging beams are compared

  28. Antibacterials • Penicillin • Alexander Fleming – 1928 • Bacteriologist • Discovered a mold that would inhibit the growth of bacteria • Published his results but. . .

  29. Howard Florey and Ernest Chain • 1941 • Isolated and purified the mold • Used it on a policeman dying of septicemia • Didn’t have enough to save him • The policeman got better and then relapsed

  30. Produced Penicillium notatum in bulk in large tanks of corn-steep liquor • 1950s the structure of penicillin was determined and synthesized Dorothy Crowfoot Hodgkin

  31. Penicillins contain a four membered beta-lactam ring. The amide group is highly reactive due to the strained angles of this ring. The ring opens and bonds to the cell walls. The R side chain can be altered to make other drugs.

  32. What it does • Prevents bacteria from making normal cell walls • Side chains can be modified to kill resistive bacteria or to withstand stomach acid • Some bacteria can make penicillianse • An enzyme that kills penicillin • Narrow spectrum antibiotic • Broad spectrum antibiotic--tetracycline

  33. Super bugs • Overuse in livestock • People who stop taking their antibiotics in mid prescription • Using it for viruses -- flu, colds. . .

  34. What is a virus? • Genetic material surrounded by a protein coat • No nucleus or cytoplasm • No cells • Reproduce inside the cells of living organisms • Constantly mutate

  35. Antivirals • Stop viruses from multiplying • Alter cell’s genetic material so the virus cannot use it to multiply • Acyclovir – cold sores • Block enzyme activity within host cell • Indinavir – HIV drug • Prevent virus from leaving the host cell • Oseltamivir (Tamiflu) and zanamivir (Relenza) • Can be prophylactic

  36. Environmental issues • Low level waste • Gives off small amount of ionizing radiation for a short time • Gloves, etc. • Can be stored on site until it can be sent to landfill or incinerated • High level waste • Gives off high of amounts of ionizing radiation for a long time • Disposal is a problem

  37. Drugs in our water • Flushing meds • Livestock waste

  38. Green chemistry • Seeks to minimize the production and release of hazardous chemicals into the environment • Sustainable chemistry

  39. Synthesis of oseltamivir • Currently uses shikimic acid as starting material • Renewable • Extracted from Chinese star anise of fermentation of glucose by genetically modified bacteria • GM bact gives higher yield

  40. Waste solvents • Contribute to 80-90% of mass • Often nonpolar and toxic • Need to be: replaced by • green solvents • Recycled • Reused • Disposed of safely • Incineration • Makes CO2 • Injected underground

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