WBR0499

Author	[[PageAuthor::Yazan Daaboul, M.D. (Reviewed by Serge Korjian)]]
Exam Type	ExamType::USMLE Step 1
Main Category	MainCategory::Pharmacology
Sub Category	SubCategory::Neurology
Prompt	[[Prompt::A pharmacologist is investigating the complex metabolism of several neuropsychiatric drugs. In one of his experiments, he administers a 20 mg intravenous (IV) bolus of phenytoin to 30 mice. He then measures the plasma concentrations of phenytoin at 5 minutes after administration, and at 2, 4, and 6 hours. Which of the following statements is true regarding the elimination of this drug?]]
Answer A	AnswerA::Phenytoin follows a flow-dependent elimination
Answer A Explanation	AnswerAExp::This is true for first-order elimination. Phenytoin on the other hand follows a capacity-limited elimination.
Answer B	AnswerB::Phenytoin follows a zero-order elimination whereby a constant proportion of the drug is eliminated per unit time
Answer B Explanation	AnswerBExp::Although phenytoin indeed follows a zero-order elimination, the same amount (not the ratio) of drug is constantly eliminated per unit time.
Answer C	AnswerC::The rate of phenytoin elimination is directly proportional to the drug's concentration
Answer C Explanation	AnswerCExp::The rate of elimination is constant regardless of concentration.
Answer D	AnswerD::Plasma concentration levels of phenytoin fall linearly with time
Answer D Explanation	AnswerDExp::Because a constant amount of phenytoin is eliminated per unit time, plasma concentration levels falls linearly.
Answer E	AnswerE::The amount of eliminated drug is gradually decreased as the plasma concentration of phenytoin is deceased over time
Answer E Explanation	AnswerEExp::The statement is true for first-order reactions. In zero-order reactions, the eliminated amount is constant regardless of plasma concentrations.
Right Answer	RightAnswer::D
Explanation	[[Explanation:: Phenytoin follows zero-order elimination kinetics. Drugs with zero-order kinetics have a constant rate of elimination regardless of the plasma concentration of the drug itself. As a result, the plasma concentration of phenytoin falls linearly as a function of time. These kinetics are characteristic of capacity-limited elimination. The elimination is constant because it is limited by the capacity of the channels. In converse, first-order elimination is proportional to the drug concentration, where a specific ratio (not amount) of the drug is eliminated per unit time. First-order elimination is called flow-dependent elimination. It is dependent on the flow of a certain drug. As the plasma concentration of a drug drops, the flow across a certain channel decreases and so does the amount of drug eliminated. Educational Objective: Phenytoin follows zero-order elimination and rate of elimination is constant per unit time. References: Katzung BG, Masters S, Trevor A. Basic and Clinical Pharmacology 12/E. Chapter 3. Pharmacokinetics & Pharmacodynamics: Rational Dosing & the Time Course of Drug Action. McGraw Hill Professional; 2012.]]
Approved	Approved::Yes
Keyword	WBRKeyword::Plasma concentration, WBRKeyword::Phenytoin, WBRKeyword::Zero order elimination, WBRKeyword::Capacity-limited elimination, WBRKeyword::Flow-dependent elimination
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