Medical Pharmacology Chapter 3: Pharmacodynamics Practice Questions

This/these drug metabolizing phase II reactions are associated with transformation of parent compound to metabolites with substantially increased water solubility.
1. Sulfation
2. Glucuronidation
3. Acetylation
4. Methylation
5. A & B
6. B & C
7. A & C
8. A B & C
9. All of the options, A, B, C & D
Most phase II drug metabolizing reactions occur on the endoplasmic reticulum (luminal side).
1. True
2. False
The rate determining step of drugs metabolized first by phase I processes and secondly by phase II processes is:
1. The phase I step, involving cytochrome p450 isoforms
2. The phase II step
This type of drug metabolizing reaction depends on a cosubstrate.
1. Phase I
2. Phase II
Expression of UGT1A1 (uridine diphosphate–glucuronosyltransferase gene) gene products (UGT1A is the locus on chromosome 2q37 49 of the 19 human genes encoding the UGT proteins.Concerning UGT1A1, choose the correct statement/statements.
1. Glucuronidation of bilirubin by UGT1A1 Is central to efficient bilirubin clearance because glucuronidation of bilirubin is rate determining.
2. The rate of bilirubin clearance is influenced by the presence of other drugs as well as by genetic variation.
3. Bilirubin, being hydrophobic resists elimination;Therefore, the glucuronidation step is required for elimination.
4. In the newborn, delayed UGT1A1 gene expression is the main reason for neonatal hyperbilirubinemia.
5. A & B
6. B & C
7. A & C
8. A, B & C
9. All the options are true; A, B, C & D
Genetic lesions in the UGT1A1 gene can result in inherited hyperbilirubinemia (lack of conjugation reactions). Example/examples include:
1. Crigler-Najjar syndrome
2. Gilbert syndrome
3. Both
4. Neither
With respect to genes associated with xenobiotic metabolism, the UGT1A1 gene is the only one essential for life due to the absolute necessity of daily serum bilirubin elimination.
1. True
2. False
The anticancer prodrug irinotecan requires activation by carboxylesterases to form a topoisomerase inhibitor exhibiting anticancer properties. This topoisomerase inhibitor, SN-38, is inactivated by UGT1A1 with subsequent biliary excretion. In patients with Gilbert syndrome, choose the correct statement/statements.
1. A patient with Gilbert syndrome will have altered responses to irinotecan.
2. Increased SN-38 blood levels, secondary to reduced glucuronidation drug inactivating reactions, can cause leukopenia and neutropenia (hematological toxicities).
3. Both
4. Neither
Sulfation reactions are involved in cholesterol catalysis with cholesteryl sulfate being an essential metabolite for keratinocyte differentiation as well as skin development.
1. True
2. False
Drug metabolism utilizing the sulfation mechanism frequently results in the generation of chemically reactive species including some linked to possible carcinogenicity.
1. True
2. False