Pad 3:51 PM bb.ndsu nodak.edu * 22% D replacement products? Case #2 A 30 year ol
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Pad 3:51 PM bb.ndsu nodak.edu * 22% D replacement products? Case #2 A 30 year old female patient comes to your retail pharmacy to pick up a prescription for Tylenol #3 (acetaminophen codeine) for pain control. You enter the prescription into the computer system and the computer's interaction checker flags an interaction between Tylenol #3 and the patient's fluoxetine prescription. Answer questions 1-3 regarding this case. 1. Fill in the blanks: Codeine is a prodrug that is metabolized to its active form, , by the enzyme Given this, what is the mechanism responsible for the drug interaction between fluoxetine and codeine? 2. Is this interaction likely to be of clinical significance? Should you bypass the interaction or call the physician? 3. What would you expect to see if you give codeine to: a) a poor metabolizer for the enzyme mentioned in #1 and b) an ultra-rapid metabolizer of the enzyme mentioned in #1. Case #3Explanation / Answer
Case#2
1.
a. Codeine is a prodrug that is metabolized to its active form, Morphine, by cytochrome p450 (CYP2D6).
b. Given this what is the mechanism responsible for the drug interaction between fluoxetine and codeine :To act, codeine is converted to its active form morphine in liver by cytochrome p450 (cyp2d6) enzyme. Fluoxetine is a strong inhibitor of CYP2D6. So co-administration of fluoxetine with codeine will make codeine ineffective as codeine will not be coverted to its active form to exert analgesic action.
2. This interaction is of moderate type which mean it has clinical significance. If patient complain of reduced control his/her pain, there is need of dose modification. Physician should be called for opinion.
3.
a. In case codeing is given to poor metabolizer, there will be less conversion of codeine to morphine and that will lead to poor control of pain. Patient will complain of pain and there may toxicity due to codeine as it will not be converted to morphine and will remain in the system.
b. In case it is given to ultra metabolizer of that enzyme, codeine will promptly converted to morphine and will show rapid action. As morphine will be metabolized by UGT normally and then excreted, there will be no codein storage or morphine storage and hence no toxicity.
Case # 3
Interaction#1 Rifampin vs Nifedipine :Rifampin will decrease the blood level or effect of nifedipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Blood level of nifedipine will be reduced.
Interaction#2 Rifampin vs amitriptyline :Rifampin will decrease the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter,by affecting hepatic enzyme CYP2C19 metabolism or hepatic/intestinal enzyme CYP3A4 metabolism. Blood level of amitriptyline will be reduced.
Interaction # 3 : ( Rifampin + lamotrigine) : Rifampin decreases levels of lamotrigine by increasing metabolism and also by increasing hepatic clearance of lamotrigine. So effect of lamotrigine will be lost.
This is not the proper dose of propranolol in home setup. At home setup minimum dose of propranolol is 40mg oral. Propranolol have variable bio-availability due to its fast-pass metabolism liver, so oral dose needed to control blood pressure is higher than IV dose.
Total plasma concenttration of lidocaine remained same but free drug concentratrion is increased. This means that there is intact metabolism and intact absorption of the drug. There is changes in the aplpha 1 acid glycoprotein concentration in plasma. There is a reduction in alpha 1 acid glycoprotein and that leads to increased free drug but total plasma concetration remained same because in proportion to increase in free drug there is decrease in protein bound drug due to reduction of that binding protein( alpha 1 acid glycoprotein).
Factor which will alter otal plasma concentration of lidocaine are:
a. Decreased metabolism of the drug due to enzyme defect or organ (where lidocaine metabolized) failure.
b. Increase in plasma alpha 1 acid glycoprotein concentration due to mycardial infarction
3. Increased dose of the drug.
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case #5
Absorption related non-liearity:
Griseofulvine at high concentration, reason: Solubility or dissolution of this drug is rate limited.
Distribution related non-linearity:
Naproxen: It becomes non linear when binding site at plasma protein is saturated.
Metabolism related non-linearity:
Phenytoin : Metabolism is limited due to enzyme saturation or in liver failure glucoronidation fails and hence metabolism is limited.
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