Drug in MRCP-Phenytoin
Although some of you may be not so familiar about phenytoin especially for those who are practicing medicine in developed countries. I think this is because there are so many new antiepileptic drugs available in the market now.
Actually, phenytoin is the oldest non-sedative antiepileptic drug introduced in 1938!!
I think it is not so important for you to understand how phenytoin acts because I myself never understand it when I was a medical student myself many years ago.
In MRCP examination, there are a few important facts that you must always remember.
Fact 1 : Drug metabolism/binding
Remember that phenytoin is mainly bound to protein. Therefore, when there is hypoalbuminemia, there is decreased protein binding- results in a decrease in total plasma concentration of drug but not the free concentration.
Therefore a lot of doctors tend to increase the drug dosage to maintain total drug levels in the therapeutic range- leading to toxicity.
Besides that remember that hepatic enzyme induction and inhibition also alter its drug level.
Although phenytoin is mainly metabolized in liver, its metabolites are excreted in kidney, therefore, renal failure may precipitate toxicity.
Fact 2: Side effects
As I remember as a medical student, there are two interesting side effects of phenytoin- gum hypertrophy ( Look out the photo at http://www.passpaces.com/ ) and generalized lymphadenopathy. However, remember that acute toxicity of phenytoin also leads to cerebellar signs!!
Fact 3: Cardiac complications
Since phenytoin alters Na, K and calcium conductance, it can cause cardiac arrhythmia, therefore always put patient on cardiac monitor if you suspect toxicity.
Also remember that chronic use of phenytoin can lead to Vitamin D metabolism abnormalities and osteomalacia.
Actually, phenytoin is the oldest non-sedative antiepileptic drug introduced in 1938!!
I think it is not so important for you to understand how phenytoin acts because I myself never understand it when I was a medical student myself many years ago.
In MRCP examination, there are a few important facts that you must always remember.
Fact 1 : Drug metabolism/binding
Remember that phenytoin is mainly bound to protein. Therefore, when there is hypoalbuminemia, there is decreased protein binding- results in a decrease in total plasma concentration of drug but not the free concentration.
Therefore a lot of doctors tend to increase the drug dosage to maintain total drug levels in the therapeutic range- leading to toxicity.
Besides that remember that hepatic enzyme induction and inhibition also alter its drug level.
Although phenytoin is mainly metabolized in liver, its metabolites are excreted in kidney, therefore, renal failure may precipitate toxicity.
Fact 2: Side effects
As I remember as a medical student, there are two interesting side effects of phenytoin- gum hypertrophy ( Look out the photo at http://www.passpaces.com/ ) and generalized lymphadenopathy. However, remember that acute toxicity of phenytoin also leads to cerebellar signs!!
Fact 3: Cardiac complications
Since phenytoin alters Na, K and calcium conductance, it can cause cardiac arrhythmia, therefore always put patient on cardiac monitor if you suspect toxicity.
Also remember that chronic use of phenytoin can lead to Vitamin D metabolism abnormalities and osteomalacia.
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