FPGEE for National Association of Boards of Pharmacy (NABP) Practice Exam

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What is the primary action in Phase I reactions during drug metabolism?

Introduction of polar functional groups

The primary action in Phase I reactions during drug metabolism involves the introduction of polar functional groups onto the drug molecules. Phase I reactions are essential for converting lipophilic (fat-soluble) compounds into more hydrophilic (water-soluble) metabolites. This transformation increases the likelihood of excretion by the kidneys or bile. Common types of reactions that occur in Phase I metabolism include oxidation, reduction, and hydrolysis. Enzymes such as cytochrome P450 monooxygenases play a pivotal role in facilitating these reactions, which often introduce hydroxyl (-OH), carboxyl (-COOH), or amino (-NH2) groups that enhance the polarity of the drug. The introduction of polar functional groups is vital, as it prepares the drug for subsequent Phase II metabolism, where these functional groups can be conjugated with another molecule to further increase water solubility, allowing for elimination from the body. In contrast, other choices do not accurately reflect the main purpose of Phase I reactions in the context of drug metabolism.

Combining drug with natural constituents

Conversion of drugs to non-polar metabolites

Oxidation of metabolites back to parent drugs

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