Question about New Goljan Rapid Review page 6

[GreenT]

So on page 6 of the Rapid Review of Pathology (new edition) is says under Smooth Endoplasmic reticulum:
Drugs like alcohol, barbiturates, and phenytoin cause SER hyperplasia and an induction of P-450 enzymes which leads to increased drug detoxification. So my question is why would this lead to "lower-than-expected therapeutic drug levels"? Wouldn't more P-450 enzymes and more drug metabolism lead to a higher than expected therapeutic drug level?
Inverse quesiton applies to the second section where he talks about inhibitors of P-450 enzymes - why higher-than expected therapeutic drug levels?

---

Members don't see this ad.

 

[GreenT]

Or did he mean that when you measure the blood plasma level in the patient with P-450 induction you will see less of the drug in the system (not that they need less drug to achieve the therapeutic effect)?

 

[gerido]

Or did he mean that when you measure the blood plasma level in the patient with P-450 induction you will see less of the drug in the system (not that they need less drug to achieve the therapeutic effect)?

I think he meant you would see the response as if it's at a lower dose in population with no induced P450 (no is relative here)

 

[ComstockOSU]

Induction of p450 results in increased breakdown of drugs that are metabolized by p450 = lower plasma levels

Inhibition of p450 results in reduced breakdown of drugs that are metabolized by p450 = higher plasma levels

 

[felicia2001uk]

Brillant..concept,concept,concept!

 

[tlbmeh]

I too was confused by the term therapeutic level because to me that implies effective dose. A person with P450 induction would have lower plasma levels of the drug and would require a higher therapeutic dose (since more is degraded).