Pharmacokinetics Final Exam 6

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  1. What categories are used to judge liver dysfunction?
    Bilirubin, Albumin, Ascites, Encephalopathy, Prothrombin Time
  2. What does the Child-Pugh classification system do?
    Assigns a grade of liver dysfuncation (A, B or C)
  3. A person with a Child-Pugh total of 7-9 will have what grade?
  4. A person with a Child-Pugh total of <7 will have what grade?
  5. A person with a Child-Pugh total of 10-15 will have what grade?
  6. What does Child-Pugh grade A indicate?
    Mild to moderate liver dysfunction
  7. What does Child-Pugh grade B indicate?
    Mild to moderate liver dysfunction
  8. What does Child-Pugh grade C indicate?
    Severe liver dysfunction
  9. What is the validated method for quantifying liver dysfunction severity and capacity to metabolize drugs?
  10. Is there a clear correlation between liver dysfunction severity and drug metabolism?
  11. Where is the best place to look information on dosage adjustment for liver disease?
    Package insert, though often absent
  12. Other than Child-Pugh, what other classification/severity systems are used?
    Discriminant Function and MELD (Mayo End Stage Liver Disease) Score
  13. What numerical value determined by the Discriminant Function describes a poor prognosis and higher risk of death?
  14. What is the MELD score used for?
    To determine the need for transplantation
  15. Generally, the higher the discriminant function score, the ________ the patient’s ability to metabolize certain drugs.
  16. Does a Child-Pugh score give the pharmacist an idea of how much to alter a dose?
    No, not quantifiable or relatable to dose
  17. What factors impact the pharmacokinetic activity of the liver?
    Hepatic blood flow, Metabolizing enzymes and Protein binding
  18. (True/False) Ascites is effected by protein binding.
  19. What is the route of an oral drug after leaving the intestine until it reaches the heart?
    Portal vein, Liver, Hepatic Vein, heart
  20. What is the equation for Hepatic Clearance (Cl H)
    Cl(H)= Qh x fu(B) x Cl(int)/ Qh + fu(B) x Cl(int) OR Cl(H)= Qh x ER(H)
  21. What does Hepatic Clearance depend on?
    Qh = hepatic blood flow, fu(B) = unbound fraction in blood and Cl(int) = intrinsic metabolic activity OR ER(H) = hepatic extraction ratio
  22. What is ER(H) = heptic extraction ratio?
    Fraction of the drug removed from the blood during a single pass through the liver
  23. What is the range of values you can have for the ER(H) = heptic extraction ratio?
  24. Define Cl(int) = intrinsic metabolic activity:
    Ability of the hepatocyte to eliminate a drug independent of blood flow or protein binding
  25. Drugs with high hepatic extraction ratio may have ___________ bioavailability.
  26. What does a portacaval shunt do?
    Reduced blood flow through the liver, affecting the clearance of high extraction ratio drugs
  27. What type of drugs are not usually as effected by altered hepatic blood flow?
    Drugs with low hepatic extraction
  28. What value is considered a High Extraction Ratio?
    > 0.7
  29. What drugs were given as an example of a high extraction ratio?
    Metoprolol, Propranolol, Labetalol, Nitroglycerin, Verapamil, Midazolam, Morphine
  30. What value is considered a Low Extraction Ratio?
    < 0.3
  31. What drugs were given as an example of a Low extraction ratio?
    Warfarin, Diazepam, Valproic acid, Phenytoin, Theophylline, Erythromycin
  32. What extraction ratio would indicate a drug that has metabolism that is independent of Hepatic blood flow?
    < 0.3
  33. What extraction ratio would indicate a drug that has metabolism that is dependent on Hepatic blood flow?
    > 0.7
  34. After first pass extraction, the bioavailability of a drug with an extraction ratio of 0.7 would be what?
  35. (True/False) CYP enzyme activity will be similar across patients with the same severity of liver dysfunction.
    False, vary widely
  36. Is phase I oxidative metabolism or phase II conjugation more sensitive to cirrhosis of the liver?
    Phase I oxidative metabolism
  37. In a patient with cirrhosis, what relative level of function would you expect for CYP2C9?
    Mild or no change in function
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Pharmacokinetics Final Exam 6
Pharmacokinetics Final Exam 6
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