Drug disposition

  1. What tissues will be enriched in lipophilic drugs?
    fat tissues
  2. Vd= equation?
    • Amout of drug in body (DOse)
    • Drug plams concentration
  3. What does cellular distribution depend on?
    • Tissue permeability
    • Perfusion rate
  4. What does the rate of tissue permeability depend on?
  5. Physiochemical properties of the drug: molecular size, pka. partition coeficient
    Physiological barriers that retrict the diffusion of drug into tissues
  6. T/F ONLY unionized/lipid soluble drugs rapidly cross the cells membrane
    • T
    • Example: thiopental, a lipophilic drug, largely unionized at blood and ECF pH readily diffuse into the brain where as pen vk which are polar and ionized do not pass b3
  7. What are the factors that make it difficult to cross the b3
    • A stealth of endothelial cells lining the capillaries
    • Tigh jxns
    • Neural tissues cover the capillaries
  8. How can you promote the passage of drug pass the b3?
    • Permeation enhancers: Dimethyl sulfoxide
    • Osmotic disruption of the b3 infusing the internal carotid artery with mannitol
    • USing dihydropylridine redox system
  9. What makes up the placental barrier?
    Trophoblast basement membrane and the endothelium
  10. T/F only highly lipid soluble drugs can cross the CSF barrier
  11. Drug dispositon
  12. what is a major determinant of drug disposition
    Drug binding to plasma protein and tissue
  13. Why is drug binding an important effect on drug dynamics?
    Because only the free drug can interact with the receptors
  14. Why is plasma binding seldom has clinical relevance?
    Because few drugs are used as displacers
  15. Fu
    • Drug plasma protein binding
    • expressed as a percent free fraction
    • Free []
    • total []
  16. Lipophilic drugs
    Pasage through lipid membranes, access to site of acition but hinders excretion
  17. What metabolites are excreted from the body?
    MOre polar, water soluble, inactive metabolites
  18. T/F MEtabolites may have potent biological activity or toxic effects
  19. Phase I
    functionalization reactions
  20. Phase II
    Conjugation reaction
  21. Where are phase I enzymes located?
  22. Where are phase II enzymes located?
  23. What are some factors affecting drug metabolism?
    • Environmental determinant: inhibition, induction
    • disease factors
    • age and sex
    • genetic variation
  24. How does environmental affect metabolism?
    • Activity of most drug metabolizing enzymes can be modulated by certain exogenous compounds
    • drugs
    • Dietary micronutrients (food preservative)
    • Environmental factors pesticides industrial compounds
  25. What is induction of drug metabolism?
    • enzyme induction is the process by which exposure to certain substrates results in accelerated biotranformation with a corresponding reduction in ummetbolized drug
    • results in the drug getting metabolized faster
  26. Can drug induce their own metaolism?
    Yes Phenobarbital carbamazepine
  27. What are four consequencces of drug induction?
    • Increased rate of metabolism
    • Decrease in drug plasma concetration
    • Reduced bioavailability
    • If the metabolite is active or reactive increase in drug effects or toxcity
  28. What is the therapeutic implications of drug induction?
    • MOst drug will decrease efficacy due to rapid metabolism but if the metabolite is active would increase the efficacy
    • Will have to change dosing
  29. What kind of process is drug metabolism?
    enzymatic process which can lead to the enzymes being ihibited therefore can an effect of the metabolism of drugs
  30. What are the types of drug enzymes inhibition?
    • Competitive
    • Irreversible inactivation of enzyme, destruction of the active site like breaking the heme group in a cyp enzyme
  31. What are the consequence of enzyme inihibtion?
    • Increase the plasma concetration of the parent drug
    • Reduction in metabolite concentration
    • Exaggerated and prolonged pharmacological effects
    • Increased likelihood of drug-induced toxicity
  32. What are the therapeutic implications of enzyme inhibition?
    May occur rapidly without any warning
  33. How can liver disease effect drug metabolism?
    Impaired drug metabolism decreased enzyme activity
  34. How can genetic variation affect drug metabolism?
    Can lead to therapeutic failure or and adverse drug reactions
  35. Genetic variation amoung enzyme can result in three phenotypes:
    • Extensive metabolizers
    • INtermediate metabolizers
    • Poor metabolizers
  36. What are actively excreted into the bile?
    • Some organic acids and bases
    • some drugs
    • Glucuronides of steroids and morphine
  37. What is the route of the enterheptatic cycle?
    Liver --> common bile duct --> small intestine --> portal vein --> liver
  38. What are the factors that affect pulmonary excretion?
    • PLamsa solubility of the drug
    • Cardiac output
    • Respiration
  39. What is the rate of pulmonary excreation proportion to?
    Drug alveolar tension of the gaseous, and inversily proportional to its plasma solubility
  40. How is urine is distilled from blood plasma in what ways?
    • Filtration
    • Re-absorption
    • Active secretion
  41. Where does active secretion of uric acid, organic acid, organic bases take place in the kidneys?
    Proximal convoluted tubule
  42. Where does reuptake of glucose aa bicarbonate tak eplace in the kidneys?
    Proximal convoluted tubule
  43. Where does reuptake of na and water?
    • Thin descending limb
    • Distal convoluted tubules
    • Collecting duct
  44. what is the major determinant in the rate of excretion of polar solutes?
    Glomular filtration rate
Card Set
Drug disposition
Drug disposition