Ribavirin:

Correct Answer: C

Rationale: Ribavirin must be taken up into cells and phosphorylated to be effective (C), converting to its triphosphate form to inhibit viral RNA synthesis, critical for its antiviral action. It's not indicated in CMV retinitis (A); ganciclovir or foscarnet are used. It inhibits viral RNA methyltransferase (B), part of its broad mechanism against RNA viruses. It's given via aerosol for RSV bronchiolitis (D), especially in infants. It's combined with interferon alfa for hepatitis C (original E). Ribavirin's efficacy in hepatitis C and severe RSV stems from its interference with viral replication and mRNA capping, though anemia is a significant side effect requiring monitoring.

Correct Answer: A

Rationale: Methotrexate inhibits dihydrofolate reductase (A), blocking tetrahydrofolate synthesis, critical for purine and pyrimidine production, halting cancer and immune cell proliferation in leukemia and rheumatoid arthritis. Folinic acid (leucovorin) rescue after high doses (B) reduces toxicity by bypassing the block. It's primarily renally excreted (C is incorrect), not biliary. Chronic use causes cirrhosis (D), a cumulative hepatotoxicity risk. It's first-line for choriocarcinoma (original E). Methotrexate's antimetabolite action is reversible, but mucositis, myelosuppression, and liver fibrosis necessitate monitoring and supportive care.

Correct Answer: B

Rationale: Aqueous hydrolysis is the correct answer because it is not a mechanism of drug permeation across biological membranes. Permeation refers to the process by which drugs move across cell membranes to reach their site of action, and it includes aqueous diffusion (A), where drugs pass through aqueous channels or pores; lipid diffusion (C), where lipophilic drugs dissolve into the lipid bilayer; and pinocytosis or endocytosis (D), where cells engulf drugs in vesicles. Special carrier transport (original E) involves specific proteins facilitating drug movement. Aqueous hydrolysis (B), however, is a chemical degradation process where a drug reacts with water, breaking chemical bonds (e.g., in esters or amides), not a physical movement across membranes. This distinction is critical in pharmacology, as permeation mechanisms determine bioavailability and tissue distribution, while hydrolysis affects drug stability, often in the gastrointestinal tract or plasma, not membrane crossing.

Correct Answer: B

Rationale: The most correct statement is that spare receptors will be detected if the intracellular effect of drug-receptor interaction lasts longer than the drug-receptor interaction itself (B). Spare receptors exist when maximal response occurs before all receptors are occupied (e.g., histamine on H2 receptors), detectable when downstream signaling (e.g., cAMP) persists post-dissociation. Option A is false; spare receptors are membrane-bound, not cytoplasmic. Option C is incorrect; maximal efficacy is set by receptor-effector coupling, not spare receptor number. Option D is wrong; receptors need agonists for activation. Option E (original) is incorrect; EC50 < Kd indicates spare receptors, not the reverse. This phenomenon increases sensitivity, explaining why low agonist doses can achieve full effects in systems like beta-adrenergic signaling.

Correct Answer: A

Rationale: Phase I involves the study of a small number of normal volunteers by highly trained clinical pharmacologists (A), assessing safety, pharmacokinetics, and tolerability (e.g., 20-100 subjects) in controlled settings. Phase II (B) tests efficacy in patients (100-300), not thousands. Phase III (C) compares efficacy and safety in larger populations (300-3000), not inducing toxicity for therapeutic index. Option D is irrelevant. Phase II with controls (original E) is true but less defining than A. Phase I's focus on healthy subjects establishes safe dosing, critical for advancing drug development, balancing risk and scientific rigor.