pharmacokinetics and dynamics

  1. Km
    concentration of substrate where enzyme is going at a 50% rate
  2. Vmax
    the point at which increasing the substrate does not make the enzyme go faster because it is maxed out
  3. Michaelis-Menten plot
    • Km = x axis at point on slope where y = 1/2Vmax
    • Vmax = y value where it flattens out
    • Image Upload 1
  4. Lineweaver-Burk plot
    • Km = -1/xint
    • Vmax = +1/yint
    • increasing abs(xint) reduces Km
    • increasing yint reduces Vmax
    • Image Upload 2
  5. reversible competitive inhibitor
    • binds active site/resembles substrate
    • Vmax unchanged (just takes substrate)
    • Km increased (=takes more substrate)
    • reduces potency
    • no effect on efficacy
  6. irreversible competitive inhibitor
    • binds active site/resembles substrate
    • Vmax reduced (some of enzyme is deactivated because it bound the wrong thing)
    • Km unchanged (the enzyme that still works is doing fine)
    • reduces efficacy
    • no effect on potency
  7. noncompetitive inhibitor
    • binds alternate site on enzyme to inhibit it
    • Vmax reduced (some of enzyme is deactivated)
    • Km unchanged (the enzyme that still works is doing fine)
    • reduces efficacy
    • no effect on potency
  8. oral bioavailability
    • depends on absorption
    • hepatic destruction
  9. IV bioavailability
  10. volume of distribution
    • lowest for large charged molecules/plasma protein bound
    • small greatest for lipophilic esp if tissue protein bound
    • chart?chf=bg,s,00000000&cht=tx&
  11. clearance
    • depends on cardiac, hepatic, renal function
    • chart?chf=bg,s,00000000&cht=tx&chl=CL%3D%5Cfrac%7Belimination..rate%7D%7B%5Bdrug%5D_%7Bplasma%7D%7D%3DV_d%5Ccdot%20K_e%20..(K_e%3Delimination..constant)&chs=952x82
  12. half life
    • time to reduce amount of drug in body by half
    • 1st order kinetics takes 4-5 half lives to reach steady state
    • chart?chf=bg,s,00000000&cht=tx&chl=t_%7B1%2F2%7D%3D%5Cfrac%7B0.693%5Ctimes%20V_d%7D%7BCL%7D%20(1st..order)&chs=402x72
  13. loading dose
    • NOT affected by renal or liver disease
    • chart?chf=bg,s,00000000&cht=tx&chl=Loading..dose%3D%5Cfrac%7BC_p%5Ctimes%20V_d%7D%7BF%7D(C_p%3Dtarget..%5Bdrug%5D_%7Bplasma%7D)&chs=772x72
  14. maintenance dose
    • affected by renal/liver disease
    • chart?chf=bg,s,00000000&cht=tx&chl=Maintenance..dose%3D%5Cfrac%7BC_p%5Ctimes%20CL%5Ctimes%20%5Ctau%7D%7BF%7D(%5Ctau%20%3D%20dose..interval)&chs=786x72
    • Cp=target [drug]plasma
    • for a continuous does just move tau to the bottom of the maintenance dose side and you're calculating a rate instead
  15. additive drug interaction
    • sum of the two effects is the total effect
    • aspirin and acetaminophen
  16. permissive drug interaction
    • presence of A is required for full effect of B
    • cortisol on catecholamine responsiveness
  17. synergistic drug interaction
    • effect of A and B is greater than the sum
    • clopidogrel and aspirin
  18. tachyphylactic drug interaction
    • acute decrease in response to drug after initial/repeated administration
    • MDMA
    • LSD
  19. zero order elimination examples
    • phenytoin
    • ethanol
    • aspirin (high/toxic concentrations)
    • constant elimination regardless of Cp
  20. weak acid examples
    • phenobarbital
    • methotrexate
    • aspirin
    • treat with bicarb (trapping it in ionized state)
  21. weak bases
    • amphetamines
    • TCAs
    • treat with ammonium chloride (trapping in ionized state)
  22. phase I metabolism
    • reduction, oxidation, hydrolysis via P-450
    • geriatric patients lose phase I first
  23. phase II metabolism
    • sulfation, acetylation, glucuronidation, glutathione conjugation, glycine conjugation, methylation
    • slow acetylators have more side effects
  24. efficacy
    • how much of a response a drug can cause
    • regardless of how much drug you have to give to generate that response (potency)
  25. EC50
    • measure of potency
    • not related to partial/full agonism
    • how much drug you need to get half the max response
    • low EC50=high potency
  26. competitive antagonist
    • binds to receptor
    • reduces potency not efficacy
    • increase EC50 (increase dose required to generate same effect)
    • can also be overcome by increasing substrate
    • dizepam (agonist) and flumazenil (comp antag)
  27. noncompetitve antagonist
    • binds to receptor
    • reduces efficacy not potency
    • cannot be overcome by increased drug or substrate
    • NE (agonist) and phenoxybenzamine (non comp antag)
  28. partial agonist (alone)
    • less effective
    • potency could be higher or lower than full agonist
  29. therapeutic index
    • TI (therapeutic index)
    • measure of safety
    • chart?chf=bg,s,00000000&cht=tx&chl=%5Cfrac%7BTD_%7B50%7D%7D%7BED_%7B50%7D%7D%3D%5Cfrac%7Bmedian..toxic..dose%7D%7Bmedian..effective..dose%7D&chs=444x78
    • safer drug has higher TI
    • LD50 replaces TD50 in animal studies
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pharmacokinetics and dynamics
yeah, they're two different things