Pharmacology Exam 1

  1. Reduction
    • Addition of hydrogen or removal of oxygen
    • R-NO2 => R-NH2
    • Enzyme is ____ reductase
  2. Hydrolysis
    • Breakdown of molecule to basic components with the addition of water
    • Ester = body breaks down into acid and alcohol
    • R-CO-O-C2H5 => R-CO-OH + HO-C2H5
    • Enzyme is Esterase
  3. Dehalogenation
    • Removal of halogen groups
    • R-C-CCL3 => HCL +R-C-CCL2
    • Dehalogenase
  4. Oxidation
    • Opposite of reduction
    • removal of hydrogen or addition of oxygen
  5. Microsomal oxidation reactions
    catalyzed by enzymes in the ER/microsome
  6. Enzyme of microsomal oxidation reactions
    • Cytochrome p450
    • Mixed Function Oxidase
    • Monooxygenase
  7. cytochrome p450
    • many members of this family
    • CYP-#ABC
    • Enzyme containes heme
    • Iron is present in oxidized (Fe3+) or reduced form (Fe 2+)
    • Reduced form has affinity for carbon monoxide
    • absorbs light maximally at 450 nm (p=peak light absorption)
  8. Mixed function oxidases
    • require O2 to work
    • require reducing agent, NADPH
  9. Monooxygenases
    use 1 oxygen atom
  10. Side chain hydroxylation
    R-CH2-CH2-CH2-CH3 => RCH2-CH2-CHOH-CH3
  11. Aromatic hydroxylation
    OH added onto aromatic ring
  12. O-Dealkylation
    • Ring-O-R => Ring-O-H + R-OH
    • Oxidation of an alkyl group
  13. N-Dealkylation
    • Ring-N-R => Ring-NH2 + R-OH
    • Oxidation of R (Alkyl group)
  14. S-Dealkylation
    • Ring-S-R => Ring-SH + R-OH
    • Oxidation of R (Alkyl Group)
  15. Sulfoxidation
    • Ring with S in the ring. S becomes double bonded to O.
    • O
    • ||
    • /S\ => /S\
  16. Aromatization
    Alicyclic compound to aromatic by aromatase in the mitochondria.
  17. Alcohol and Aldehyde oxidation reactions
    • Alcohol dehydrogenase
    • R-OH => Aldehyde => Acid
    • Aldehyde dehydrogenase
    • Located in cytosol and mitochondria
    • Cytosolic enzymes are more efficient than mito
  18. specific inhibitors of alcohol dehydrogenase
  19. Specific inhibitor of aldehyde dehydrogenase
  20. Mono and Di-amine oxidation reaction
    • monoamine oxidase and diamine oxidase
    • present in the mitochondria
    • Mono = 1 amino group
    • Di = 2 amino groups
  21. Purine oxidation
    • chemical structure is the nucleus in caffeine, theophyline or hypoxanthine
    • converts to uric acid
    • metabolized by xanthine oxidase
  22. xanthine oxidase
    • catalyzes oxidation of purines
    • present in the cytosol
  23. inhibitor of xanthine oxidase
  24. Cytosolic Enzymes
    soluble fraction
  25. Conjugation reactions
    • Glucuronidation
    • Sulfation
    • Acetylation/acylation
    • Glutathione conjugation reactions/mercapturic acid formation
  26. Glucuronidation Reactions
    • addition of glucuronic acid to the drug
    • uses glycuronyl transferases
    • high capacity, low affinity
  27. UDPGA
    uridinediphosphoglucuronic acid
  28. Glucuronyl transferases
    • moves glucuronic acid from UDPGA to the drug
    • enhances water solubility of drug
    • also present in microsomes
  29. sulfation reaction
    • addition of sulfate group to the drug molecule
    • active sulfate compound required
  30. PAPS
  31. sulfur transferases/sulfur kinase
    • trasfer sulfur from PAPS to drug in sulfation reaction
    • present in cytosol
    • high affinity, low capacity
    • low amounts of PAPS limit the reaction
  32. Acetylation
    • two carbon compound added to the drug by acetyltransferase
    • present in cytosol
  33. acylation
    • more than two carbons added to drug by acyltransferase
    • present in cytosol
  34. Glutathione conjugation reactions
    involve the tri-peptide glutathione
  35. glutathione
    • tri-peptide
    • cysteine - glutamate - glycine
  36. Reduced form of glutathione
    • CYS - SH or G-SH
    • Interacts with drugs enzymatically or non-enzymatically
  37. Oxidized form of Glutathione
    • cross link between two glutathione molecules by S=S
    • GSSG
  38. Glutathione S Transferase
    • found in the cytosol
    • forms a glutathione adduct on the drug to be excreted
  39. Mercapturic Acid Derivative
    • Depends on the drug attached to glutathione
    • drug is attached to glutathione
    • body removes glycine and glutamate then reacts with cysteine via acetylation.
    • Drug-S-CYS-NH-O-CO-CH3
  40. Effect of diet on metabolism
    • Diet effects proteins
    • May change enzymes
    • High protein, low carb may increase metabolism
    • High carb, low protein my decrease drug metabolism
  41. High Fat diet effects on metabolism
    May induce metabolism of certain drugs by enducing specific enzymes
  42. Effects of age on metabolism
    • drug metabolism decreases
    • decline in microsomal enzymes is more than in non-microsomal.
  43. Environmental Effects on Metabolism
    • Temperature
    • Stress
    • Smoking, first or second hand
    • Genetics
    • Disease states (liver = decrease metabolism)
  44. Drug excretion
    Termination of the drug by inactivation or redistribution
  45. Major routes of excretion
    • Renal
    • Biliary (through the liver)
    • Lungs (excretion of volatile molecules)
  46. Minor routes of excretion
    • Sweat
    • Tears
    • Saliva
    • Milk
  47. Major Mechanisms of Drug excretion in the kidney
    • Filtration from blood to glomerulus
    • Secretion from blood to glomerulus
    • Reabsorption from urine to blood
  48. Filtration from blood to glomerulus
    • drug must be small
    • must be free drug
    • blood pressure pushes molecules out of blood vessel and into the nephron
    • drug moves from high concentration to low concentration
  49. Secretion of drugs
    • Active transport process
    • Carrier mediated process
    • Involves saturability, specificity, energy
    • moves from low to high concentration
    • useful for drugs that cannot cross lipid membranes due to size or charge
  50. Reabsorption of the drug
    • from urine to blood
    • drugs that are able to cross lipid membranes of the nephron
    • Must be unionized to cross membrane
  51. Mechanisms to keep drug in the urine
    • Drug must be kept in the ionized form in the urine
    • keep pH low in the urine
  52. Mechanisms to push drugs from blood to urine
    increase the pH of the blood to make a basic drug move (unionized form) move into the urine
  53. Hasten drug removal in the urine
    • Ionize the drug in the urine
    • drink a lot of fluids
    • Ingest NH4CL (ammonium chloride) which acidifies urine
  54. Mechanisms to keep a drug in the body
    • Keep drug unionized
    • Remove H+ from the urine (increase pH)
    • Alkalinize the urine with sodium bicarb
  55. Keep weak acid drug in the urine
    • Alkalinize urine
    • results in A- and H+
  56. Biliary Secretion
    • Carrier mediated
    • could administer a drug that has a higher affinity for a carrier for the drug you want to stay, to keep a drug in the system.
  57. Diets that acidify urine
    meat and fish
  58. diets that alkalinize urine
  59. competes with sodium for a carrier
  60. Effects of aging on drug excretion
    • Diminished blood supply to kidney and liver
    • Proteins of transport mechanisms decreased
    • Energy diminished
Card Set
Pharmacology Exam 1