Term
| What are the 4 steps to solving a therpeutic problem? |
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Definition
1) Determine if the problem is due to
a) disease progression despite therapeutics
b) new , unrelated disease
c) therapeutic problem
2) Determine if the adverse effects are due to subeffective levels or toxic level of the therapeutics
3) Determine the basis for drug interation
4) Remedy the problem |
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Term
57 y/o woman with end-stage renal disease underwent allograft transplant. She was given a regimen of prednisone, azathioprine & tacrolimus.
Two years later, she was given nefazodone for depression.
After 1 week of nefazodone therapy, patient experienced headache, confusion & "gray areas" in her vision w/ no abnormal ophthalmologic findings. Serum creatinine was elevated.
Assume step one was completed to rule out new disease & disease progression.
Step 2: Why do we know that this is not due to subeffective levels of therapeutics? |
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Definition
Though elevated serum creatinine is indicative of allograft rejection, her neurological findings do not fit.
Also, subeffective levels of nefazodone would produce depression. |
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Term
57 y/o woman with end-stage renal disease underwent allograft transplant. She was given a regimen of prednisone, azathioprine & tacrolimus.
Two years later, she was given nefazodone for depression.
After 1 week of nefazodone therapy, patient experienced headache, confusion & "gray areas" in her vision w/ no abnormal ophthalmologic findings. Serum creatinine was elevated.
Step 2: What Sx are expected from the 4 therapeutics she's on?
What one is suspected to be toxic for this patient? |
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Definition
1) Prednisone: Cushingoid
2) Azathiopine: bone marrow depression
3) Nefazodone: neurotoxicity - xerostomia (strange taste), sedation, visual disturbances can occur
4) Tacrolimus: nephrotoxicity - increased serum creatinine, neurotoxicity - headache, confusion, & visual disturbances.
Suspected tacolimus toxicity |
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Term
57 y/o woman with end-stage renal disease underwent allograft transplant. She was given a regimen of prednisone, azathioprine & tacrolimus.
Two years later, she was given nefazodone for depression.
After 1 week of nefazodone therapy, patient experienced headache, confusion & "gray areas" in her vision w/ no abnormal ophthalmologic findings. Serum creatinine was elevated.
Step 3: What is the basis for her tacrolimus toxicity? |
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Definition
tacrolimus has low variable absorption & is metabolized by CYP3A4 and is then excreted in bile.
Nafzodone is also metabolized by CYP3A4.
Therefore they are competitive inhibitors of one another's metabolism, but the toxicity of tacolimus is more apparent. |
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Term
57 y/o woman with end-stage renal disease underwent allograft transplant. She was given a regimen of prednisone, azathioprine & tacrolimus.
Two years later, she was given nefazodone for depression.
After 1 week of nefazodone therapy, patient experienced headache, confusion & "gray areas" in her vision w/ no abnormal ophthalmologic findings. Serum creatinine was elevated.
Step 4: How should her treatment regimen be remedied? |
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Definition
| decrease dosage of tacrolimus & monitor patient's serum levels. |
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