Материал: 2016_Kaplan_USMLE_Step_1_Lecture_Notes_Pharmacology

Section I λ General Principles

8.Answer C. Azole antifungals (e.g. ketoconazole) are inhibitors of cytochrome P450 enzymes, especially CYP3A4, the most abundant isozyme form in the human liver. The 3A4 isozyme metabolizes a wide range of drugs. Ketoconazole would actually raise the plasma levels of oral contraceptives increasing the risk of side effects but it would not reduce their effectiveness. All other drugs listed are P450 inducers. As such, they would tend to lower plasma levels and decrease effectiveness of oral contraceptives.

9.Answer A. The typical log dose response figure with the parallel nature of the curves suggests that the three drugs are interacting with the same receptor system. Drugs A and B are full agonists because they achieve the maximal response. They have the same efficacy. Drug A is more potent than drugs B or C. Drug B is more potent than drug C. Drug C is a partial agonist with less efficacy than the full agonists.

10.Answer C. The fact that the drug has therapeutic efficacy for 6 h has no direct relationship to its half-life—it simply means that the drug is above its minimal effective concentration for 6 h. Doubling the dose (to 1 g) means that the drug level will be above the minimum for a longer period. Because the elimination half-life is 8 h, 500 mg of the drug will remain in the body 8 h after a dose of 1 g. Thus, the total duration of effectiveness must be 8 + 6 = 14 h.

11.Answer E. In first-order kinetics, the elimination rate of a drug is directly proportional to its plasma concentration, which in turn is proportional to the dose. Drugs that follow first-order elimination have a constant elimination half-life similar to the example given in the question. Likewise, clearance and volume of distribution are pharmacokinetic characteristics of a drug that do not routinely change with dose, although they may vary in terms of disease or dysfunction.

12.Answer B. The patient in the question has renal dysfunction which reduces renal clearance. This would necessitate a lower maintenance dose for medications such as acetaminophen.

clearance while the loading dose equation does not. The t ½ of acetaminophen would be increased in this patient due to the decrease in clearance, but the Vd would be unaffected.

14.Answer B. The rules for time to steady-state are that it takes 4-5 t ½ to reach clinical steady-state. It also takes one t ½ to get half way to steady-state. Since the drug got 50% of the way to steady-state in 6 hours, its t ½ must be 6 hours.

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Chapter 3 λ Practice Questions

15.Answer D. At 6 h after IV injection (which corresponds to two half-lives of the drug), the plasma level is 5 mg/L. Extrapolating back to zero time, “doubling” plasma level for each half-life results in an initial plasma level at zero time (C0) = 5 mg/L × 2 × 2 = 20 mg/L.

Dose = C0 x Vd

=20 mg/L × 10 L

=200 mg

16.Answer C. MD = Cl × Css × τ

Since the drug was given by constant IV infusion there is no need to consider the dosing interval (τ). Therefore, 400 mg/h = 50 L/h x Css

400 mg/h ÷ 50 L/h = 8 mg/L

Alternatively, you could evaluate the question this way:

An infusion rate (k0) is given by:

k0 = Cl × Css rearrange: Css = k0/Cl

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SECTION II

Autonomic

Pharmacology