DRUG DEVELOPMENT AND REGULATION Flashcards
Q: What are CYP enzymes and their importance in drug metabolism?
A: CYP enzymes are multi-function enzymes with low substrate specificity, which means they can metabolize many different drugs. They are important because they can be readily inhibited or induced by different substances, affecting drug metabolism and therapy.
Q: How does grapefruit juice affect CYP3A4?
A: Grapefruit juice inhibits CYP3A4, an enzyme important for drug metabolism. This inhibition can lead to increased blood levels of drugs metabolized by CYP3A4, potentially causing toxicity.
Q: What is a significant risk of CYP3A4 inhibition by grapefruit juice?
A: The significant risk is that the drug can stay in the system longer, leading to potential toxicity because the body can’t metabolize and eliminate it efficiently.
Q: What happens during Phase II metabolism?
A: In Phase II metabolism, Phase I metabolites are conjugated with very polar endogenous molecules, making them more water-soluble and easier to excrete through urine or feces.
Q: How can Phase II metabolism affect drug elimination?
A: It makes drug molecules more hydrophilic (less hydrophobic), thus facilitating their elimination from the body.
Q: What is the role of UGT1A1 in drug metabolism?
A: UGT1A1 is an enzyme involved in the glucuronidation process, which helps detoxify drugs like irinotecan by adding a glucuronic acid molecule, making them more water-soluble for excretion.
Q: Define Clearance (Cl) in pharmacokinetics.
A: Clearance is the volume of plasma from which a drug is completely removed per unit time. It’s a measure of the efficiency of drug elimination from the body.
Q: What is the Volume of Distribution (Vd)?
A: Volume of Distribution is a theoretical volume that a drug would need to be evenly distributed to achieve the same concentration as in the blood plasma. A higher Vd indicates more extensive distribution into tissues.
Q: What are kinase inhibitors and their role in cancer treatment?
A: Kinase inhibitors are drugs that block specific enzymes (kinases) involved in the growth and survival of cancer cells. For example, imatinib targets the BCR/Abl fusion protein in chronic myelogenous leukemia (CML).
Q: What is the significance of the BCR/Abl fusion gene in CML?
A: The BCR/Abl fusion gene results from a chromosomal abnormality and drives abnormal kinase activity, promoting uncontrolled cell division in CML.
Q: What are some adverse effects of kinase inhibitors like imatinib and sorafenib?
A: They can cause hand-foot syndrome, dermal toxicities, gastrointestinal toxicities, and other side effects due to their action on kinases in normal cells as well.
Q: How does glycine neurotransmission affect pain perception?
A: Glycine acts as an inhibitory neurotransmitter in the spinal cord. Enhancing glycine activity can reduce pain perception by inhibiting excitatory neurons.
Q: What is the Blood-Brain Barrier (BBB) and its significance in CNS drug delivery?
A: The BBB is a protective barrier that prevents toxins and other substances from entering the CNS. Drugs targeting the CNS must cross this barrier to be effective.
Q: What is the role of the Pharmaceutical Benefits Scheme (PBS) in drug regulation?
A: The PBS provides a list of subsidized medicines available to patients. The Pharmaceutical Benefits Advisory Committee (PBAC) decides which medicines are included based on cost-effectiveness and health outcomes.
Q: What are the 3 Rs considered in animal research ethics?
A: Replacement (using alternative methods), Reduction (using fewer animals), and Refinement (minimizing harm and improving welfare).
