By Domenic A. Ciraulo MD, Richard I. Shader, David J. Greenblatt MD, Wayne L. Creelman MD
Thoroughly up to date for its 3rd variation, this guide presents entire, present, and simply available info on how psychotropic medicines engage with each other and with compounds used to regard non-psychiatric health conditions. The booklet is prepared for swift reference, comprises a variety of tables, and gives guidance for handling opposed effects.
The 3rd version contains an adversarial drug results desk within the appendix part, tables on receptor binding and dosing, and the newest info on medicinal drugs of abuse and chemical dependence. This version additionally comprises drug-food interactions for every drug type and interactions of psychotropic medicinal drugs with HIV medications.
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Rifampin treatment increases the clearance of lamotrigine, zidovudine, acetaminophen, codeine, and morphine, suggesting that the UGTs mediating these biotransformations are inducible via PXR activation. Taken together, these observations suggest that UGTs in both subfamilies 1A and 2B may be inducible via all three mechanisms: Ah receptor activation, CAR activation, and PXR activation. qxd 7/28/05 3:25 PM Page 37 pinnacle Raj01:BooksQuark:GRBQ043-Cirualo:F 1. CONCEPTS AND MECHANISMS OF DRUG DISPOSITION 37 glucuronidation are smaller than that observed with CYP induction.
Although these polymorphisms can affect enzymatic activity in a substrate-dependent manner, in the majority of cases, the *2 variant exhibits decreased activity, whereas the *3 variant results in an almost complete loss or dramatic reduction in enzyme activity. Thus, individuals homozygous for the *3 allele are classified as CYP2C9 poor metabolizers (PMs) and have significantly lower clearance of CYP2C9 substrate drugs. In the cases of drugs with narrow therapeutic windows, such as warfarin or phenytoin, such individuals have significantly lower dosage requirements to produce the desired level of anticoagulation or antiepileptic effects without bleeding or CNS toxicity, respectively.
Low therapeutic index drugs like warfarin, tolbutamide, phenytoin, carbamazepine, and valproic acid have been traditionally considered as likely victims of displacement interactions. This is in part due to the observation of clinically significant interactions in which the extent of their plasma protein binding was decreased. , warfarin–phenylbutazone, tolbutamide–sulfaphenazole) is in fact, metabolic inhibition by the perpetrator agent. 1, making an alteration of plasma protein binding inconsequential from a clinical standpoint.