Pharmacokinetics Final Exam 7

  1. In a patient with cirrhosis, what relative level of function would you expect for CYP2D6?
    Somewhat altered
  2. In a patient with cirrhosis, what relative level of function would you expect for CYP2C19?
    High sensitivity, large change
  3. Drugs using metabolic pathways effected by liver dysfunction will have higher or lower concentrations, why?
    Higher, less active metabolism leading to excretion
  4. In general liver disease increases or decreases serum drug concentration?
    Increases
  5. Does protein binding change with liver disease?
    Yes
  6. Why does protein binding change with liver disease?
    Many drug binding proteins are made by the liver, cirrhosis decreases production of these proteins
  7. What transporting/drug binding proteins are often of concern with liver disease?
    Albumin and Alpha-1-acid glycoprotein
  8. Is there a clear way to quantify the effect of decreased proteins on drug pharmacokinetics?
    No, no method
  9. Will you have more or less free drug with liver disease due to changes in protein carriers?
    More
  10. With lower amounts of protein binding, will you have more or less free drug entering the hepatocytes?
    More
  11. (True/False) Bound or unbound drug can enter the hepatocyte. False, only unbound can enter the hepatocyte
  12. When considering a dose for a patient with liver dysfunction what parameter would likely be most useful to measure?
    Fu (free drug fraction)
  13. Pharmacokinetic changes in drug concentration may not be reflected in ___________ drug concentration, but instead only reflected in the ___________ fraction.
    Total, Free
  14. What drugs were given as examples of highly protein bound?
    Warfarin, Propranolol, imipramine, Amitriptyline, Diazepam, Chlorpromazine
  15. What type of drugs are most effected by first pass metabolism?
    High ER drugs
  16. In severe cirrhosis, what level of first pass metabolism exists?
    Basically no longer exists
  17. In high ER drugs how important is protein binding, why?
    Not very because only a small protion is available for binding
  18. If a patient has decreased clearance and increased t1/2, what would you expect the AUC to be?
    Larger
  19. What is acute liver disease caused by?
    Drug overdose, etc.
  20. What are the main issues that need to be addressed with Acute liver disease?
    Hepatocellular function = possible reduced availability or capacity of metabolizing enzymes
  21. What are the main issues that need to be addressed with Chronic liver disease?
    Alterations in hepatic blood flow, altered protein binding and possible increased Vd if ascites is present
  22. Why can Vd increase in hepatic failure patients?
    Ascites
  23. What is the “3rd” spacing?
    Ascites fluid space
  24. What effect can ascites have on drug kinetics?
    Create “3rd Spacing”, increase total body weight effecting dosing, increase Vd of aquaphilic drugs (aminoglycosides, Vanco)
  25. Hepatic encephalopathy (HE) can cause what changes in drug parameters?
    Pharmacodynamics of the drug and Additive cognitive effects of some CNS drugs
  26. What is Hepatic encephalopathy (HE)?
    Liver disease patient has a buildup of drugs/toxins in the brain
  27. Patients with liver disease have a lower or higher sensitivity to many drugs?
    Higher
  28. The greater effect of some drugs on patients with liver disease is especially noticeable with what drug class?
    Those acting on the CNS (especially benzodiazepine)
  29. Why is there a greater effect of some drugs on patients with liver disease?
    Increased BBB penetration
  30. Why is it hard to differentiate the symptoms of hepatic encephalopathy?
    Similar symptoms to the enhanced CNS effects of some drugs in patients with liver disease
  31. What drugs were given as an example for greater penetration in to the CNS in patients with liver disease?
    Cimetidine, Ranitidene, Quinolones, Benzodiazapine
  32. What are the major drug classes that are effected by liver disease?
    Benzodiazapine, Estradiol and some Beta blockers, ACEIs, ARBs, CCBs, Antiarrhythmatics, SSRIs
  33. What Benzodiazapines are not associated with pharmacokinetic changes and are safe to use in liver disease?
    Larazepam, Oxazepam, Temazepam
  34. Why are some Benzodiazapines unsafe for use in liver disease?
    Increased CNS effect
  35. Why is Estradiol not safe in patients with liver disease?
    Requires liver transformation become active, highly protein bound and has high first pass metabolism
  36. What beta blockers are not a good choice in liver disease?
    Nebivolol, Carvedilol
  37. Why are ACEIs not a good choice for liver disease patients?
    Need to be activated by the liver
  38. What ACEI does not need liver activation and so can be used in liver disease patients?
    Lisinopril
  39. What ARBs are not a good choice for patients with liver disease and why?
    Losartan and Valsartan, because they have increased AUC
  40. What ARB is not affected by liver disease?
    Irbesartan
  41. Why are most CCBs not a good choice for patients with liver disease?
    Increased AUC
  42. What antiarrhythmatics are not a good choice for liver disease patients?
    Flecainide, Mexiletine, profenone
  43. Why are the antiarrhythmatics: Flecainide, Mexiletine, profenone not a good choice for patients with liver disease?
    Decrease Clearance and increase AUC
  44. What SSRIs have been shown to increased AUC in patients with liver disease?
    Fluvoxamine, Fluoxetine and paroxetine
  45. Can you usually look up dose changes necessary for liver disease patient in the package insert?
    No, not usually there
  46. Drugs with what characteristics are worrisome for patients with liver disease?
    High ER, High Protein binding and Highly aquaphilic drugs
  47. When are highly aquaphilic drugs a concern for use in liver disease patients?
    When ascites is present
Author
kyleannkelsey
ID
248894
Card Set
Pharmacokinetics Final Exam 7
Description
Pharmacokinetics Final Exam 7
Updated