PHA 5127

Problem Set
"Drug Metabolism"

1. Tilidine is a narcotic analgesic which can be abused by drug addicts when taken in high doses. Naloxone is an opiate antagonist which blocks the action of tilidine. It is known to undergo a saturable first pass effect. What is the rationale for a drug combination tilidine/naloxone (valoron)?

 

2. Administration of phenobarbital (60 mg daily) to a patient receiving dicumarol (75 mg daily) chronically, reduces the plasma concentration of the anticoagulant (black circle) and the prothrombin (open circle) time, a measure of its effect on the concentration of the vitamin k1-dependent clotting factors.


What kind of pharmacokinetic interaction is responsible for the observed pharmacodynamic interaction? Explain your answer.

3. Discuss following statement:

For drugs with a hepatic extraction ratio of 1, the hepatocyte does not represent a strong diffusion barrier.



4. Select for the following physiological changes the induced change on the pharmacokinetic parameters for a lipophilic, protein bound, low extraction drug cleared by liver and kidney.



Physiological change effect on kinetics
1. increase in plasma protein_____ a. Cltot ­
2. increase in blood flow____ b. Vd ¯
3. decrease in metabolic liver enzymes____ c. Vd ­
4. decrease in creatinine clearance_____ d. khep/kren ­
5. increase in the number of fat cells_____ e. Clint ¯
6. blood flow at the absorption site_____ f. Clhep ­
  g. none of the above effect

 

5. Mark whether the following statements are True or False

gut wall metabolism is one example of the first-pass effect.

enterohepatic recycling can prolong drug activity in the body.

biliary obstruction decreases the half-life of a drug subject to biliary excretion.

most drugs only pass through the liver once.

if hepatic blood flow is reduced, more drug will get metabolized.

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