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False positive test
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High sensitivity of screening test
Malignancy
Medication interaction
Medication noncompliance
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This patient is presenting with an alcohol withdrawal seizure in the setting of a seizure disorder and is started on phenobarbital which can reduce the efficacy of oral contraceptive pills. This interaction most likely explains her current pregnancy. Phenobarbital is commonly used to control seizure disorders and to treat alcohol withdrawal. It is favored in alcohol withdrawal because of its long half-life (48-72 hours); thus, patients have good control of their symptoms for a prolonged period of time. However, phenobarbital is a substrate for CYP2C19, CYP2C9, and CYP2E1. It is an inducer for the cytochrome P450 (CYP) system including CYP1A2, CYP2A6, and CYP3A4. This will subsequently increase the metabolism of medications metabolized by these CYP enzymes including phenytoin, carbamazepine, rivaroxaban/apixaban, and some human immunodeficiency virus (HIV) medications. Increased metabolism of these drugs can last for weeks given the long half-life of phenobarbital; thus it should be used with caution. The doses of other medications metabolized by CYP enzymes may need to be increased during the period of phenobarbital use, or phenobarbital should be avoided. Rosenson et al. discuss the use of phenobarbital in conjunction with benzodiazepines to control alcohol withdrawal. The authors found that this combination did not result in increased adverse events but did reduce ICU admissions. They recommend using phenobarbital for alcohol withdrawal, especially in severe cases. Incorrect Answers: Answer 1: False positive test is possible in any diagnostic test and represents a positive result with a negative underlying diagnosis. Though this is plausible, it is less likely than a true positive test given her phenobarbital use. An hCG quantitative level could rule out this possibility. Answer 2: High sensitivity of screening test describes a test that picks up most cases of patients with the disease of interest. If the cutoff value of a pregnancy test was lowered it would be more sensitive and less specific. This is a possible but less likely explanation for this patient's positive pregnancy test. Answer 3: Malignancy such as choriocarcinoma may result in an elevated human chorionic gonadotropin (hCG) level. A choriocarcinoma is composed of syncytiotrophoblasts which normally releases hCG. Choriocarcinoma is a small hemorrhagic tumor with early hematogenous spread and poor response to chemotherapy. Answer 5: Medication noncompliance is a common cause of medical issues and is possible in this patient. However, she states she has been taking her medications as prescribed and there is an alternative explanation for why her oral contraceptive pills are not working. Bullet Summary: Phenobarbital is a CYP enzyme inducer and can thus decrease the efficacy of many common medications, including oral contraceptive pills.
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