Pharm_01.txt

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c_sopkovich
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59588
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Pharm_01.txt
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2011-01-13 11:49:14
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Pharmacy
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Chapter 1: Basic Principles
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  1. Medical pharmacology
    area of pharmacology concerned with the use of chemicals in the prevention, diagnosis, and treatment of disease
  2. Toxicology
    area of pharmacology concerned with the undesirable affects
  3. pharmacokinetics
    the effects of the body on the drug
  4. pharmacodynamics
    actions of the drug on the body
  5. What mediated drug actions
    receptors in the body
  6. Drug enantiomers
    • can differ in their affinity for the receptor
    • different rates of metabolism
  7. common molecular weight of drugs
    • 100-1000
    • drugs smaller then 100 are not selective enough
    • larger then a 1000 are poorly absorbed and distributed
  8. bonds of drugs to receptor
    • covalent; very strong, usually irreversible
    • electrostatic bonds; weaker, between a cation and anion
    • weak interactions; van der waals, hydrophobic bonds
  9. agonist
    if the drug results in activation after binding
  10. antagonist
    if the action of the drug is inhibition
  11. allosteric activators/inhibitors
    bind to the the receptor not at the active site but elsewhere that causes a conformational change that increases or decreases the affinity of the receptor for its substrate
  12. inert binding sites
    • drugs can bind to nonregulatory molecules in the body, does not produce any effect.
    • can play a large role in buffering the concentration of a drug because bound drug does not contribute to the drugs concentration gradient
  13. three phases of pharmacokinetics
    • absorption
    • distribution
    • elimination
  14. permeation
    movement of a drug into and within the biologic environment
  15. aqueous diffusion
    • the movement of a molecule through the watery extracellular and intracellular spaces
    • most capillaries of the body have small water filled pores that allow for passive diffusion
  16. lipid diffusion
    the passive diffusion of molecules through membranes and lipid structures
  17. Probencid
    • inhibits transport of uric acid, pcn, and other weak acids in the nephron
    • used to increase the the excretion of uric acid in gout
    • metabolism of nucleic acid purene
  18. p-glycoprotein transport molecules
    found to cause cancers to become drug resistant by transporting the drug out of the cell
  19. endocytosis
    allows very large or insoluble molecules to enter the cell
  20. Ficks law
    • used to predict the rate of movement across a barrier
    • takes into account the permeability coefficient, aream thickness of the barrier
    • rate= concentration difference x area x (permeability coefficient / thickness)
    • shows drug absorption is faster through organs with the largest surface area; small intestine
  21. molecular change
    • unchanged particles are more lipid soluble
    • charged particles are more water soluble
  22. protonation of weak acids and bases
    • protonation of a weak base ionizes it
    • protonation of a weak acid is neutral and lipid soluble
  23. filtration of drugs at the glamerulous
    most drugs are filtered freely but lipid soluble drugs are easily reabsorbed
  24. How do you increase excretion in an aspirin overdose
    • aspirin is a weak acid
    • accelerate excretion by alkalinizing the urine, give bicarb
    • the alkaline urine will cause the acid the deprotonate and become charged and excreted
  25. Increase excretion of a weak base
    • pyrimethamine, amphetamine
    • give ammonium chloride to acidify the urine and protonate the weak base
  26. Bioavailability
    the amount of drug absorbed divided by the amount given
  27. First pass effects
    when a drug is taken orally it is absorbed into the hepatic circulation and subjected to deactivation by the liver
  28. danger of intravenous administration
    • the high blood levels of the drug are reached very quickly
    • 100% bioavailability
  29. What class of drugs can not be given intramuscular
    • anticoagulants such as heparin
    • can cause bleeding and a hematoma in the muscle
  30. First pass with rectal administration
    most will avoid the hepatic circulation but some of the drug will tend to migrate upward to the superior rectal veins and will be carried to the portal vein by the inferior mesenteric veins
  31. How does blood flow affect absorption
    a faster blood flow increases absorption through the subcutaneous and intramuscular administration
  32. determinants of distribution
    • size; the larger the organ the more drug in can absorb because the concentration in the organ does not rise too much. Skeletal muscle is a very large organ and keeps a large blood to tissue concentration gradient
    • blood flow; well perfused tissue will achieve a higher concentration sooner
    • solubility; the solubility on the tissue will influence concentration in the perivascular extracellular space. if the drug absorbs into cells readily then more drug will be absorbed into the extra cellular space out of the vasculature
    • Binding; binding of a drug to macromolecules increases the drugs concentration in that compartment. Example is warfarin, it strongly binds to albumin which restricts its diffusion out of the vascular compartment
  33. Vd relates the amount of drug in the body to the concentration in the plasma
  34. Prodrugs
    • administered as inactive compounds that must be metabolized to become active
    • levadopa, minoxidil
  35. Drug elimination is not the same as excretion
    • drug can bind irreversibly to its receptor
    • metabolised
    • phenoxybenzamine, an irreversible alpha antagonist, is eliminated by binding alpha receptors
  36. first order elimination
    • the rate of elimination is directly proportional with the drugs concentration
    • the higher the concentration the more eliminated per unit time
    • half life is constant regardless of the amount of drug in the body
    • This is most drugs in clinical use
  37. zero order elimination
    • the rite of elimination is constant regardless of concentration
    • occurs with drugs that saturate there elimination mechanism at clinical doses
    • ethanol

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