USMLE IUSMLE I

1. The pharmacokinetic properties of a 1. The pharmacokinetic properties of a new antihistamine are being studied in new antihistamine are being studied in normal volunteers during phase I clinical normal volunteers during phase I clinical trials. The clearance and half-life of the trials. The clearance and half-life of the drug are determined to be 4.0 L/hour and drug are determined to be 4.0 L/hour and 10 hours, respectively. Which of the 10 hours, respectively. Which of the following values is the approximate following values is the approximate volume of distribution for this drug?volume of distribution for this drug?

A. 0.06 LA. 0.06 L B. 14 LB. 14 L C. 45 LC. 45 L D. 60 LD. 60 L E. 130 LE. 130 L

The correct answer is D. The volume of The correct answer is D. The volume of distribution of a drug can be distribution of a drug can be determined using the following determined using the following equation: equation:

t1/2 = (0.693 x Vd)/CLt1/2 = (0.693 x Vd)/CL Therefore, 10 hours = (0.693 x Therefore, 10 hours = (0.693 x

Vd)/(4.0 L/hour),Vd)/(4.0 L/hour), 40 hours = 0.693 x Vd,40 hours = 0.693 x Vd, Vd = 58 L which is approximately 60 LVd = 58 L which is approximately 60 L

2. A cardiovascular pharmacologist is 2. A cardiovascular pharmacologist is researching the effects of new compounds on researching the effects of new compounds on arteriolar resistance. Drug X maximally arteriolar resistance. Drug X maximally increases vascular resistance by 50% at a increases vascular resistance by 50% at a dose of 20 mg/mL. Drug Y maximally dose of 20 mg/mL. Drug Y maximally increases vascular resistance by 75% at a increases vascular resistance by 75% at a dose of 40 mg/mL. Which of the following dose of 40 mg/mL. Which of the following conclusions can the researcher draw from this conclusions can the researcher draw from this experiment?experiment?

A. Drug X has a smaller volume of distribution A. Drug X has a smaller volume of distribution than Drug Ythan Drug YB. Drug X has a shorter half-life than Drug YB. Drug X has a shorter half-life than Drug YC. Drug X is less efficacious than Drug YC. Drug X is less efficacious than Drug YD. Drug X is less potent than Drug YD. Drug X is less potent than Drug YE. Drug X has a lower LD50 than Drug YE. Drug X has a lower LD50 than Drug Y

The correct answer is C. The correct answer is C. The only The only conclusion that can be drawn from this conclusion that can be drawn from this data is that Drug X is less efficacious than data is that Drug X is less efficacious than Drug Y. Efficacy is defined as the maximum Drug Y. Efficacy is defined as the maximum effect that can be produced by a drug, effect that can be produced by a drug, regardless of dose. Drug X can only regardless of dose. Drug X can only produce a 50% change in resistance, produce a 50% change in resistance, whereas Drug Y can produce a 75% change whereas Drug Y can produce a 75% change in resistance. Therefore, Drug X is less in resistance. Therefore, Drug X is less efficacious than Drug Y.efficacious than Drug Y.

3.The pharmacokinetic properties of a 3.The pharmacokinetic properties of a new drug are being studied under phase new drug are being studied under phase 1 clinical trials. The vol of distribution 1 clinical trials. The vol of distribution and clearance of the drug is 80 l and 3 l and clearance of the drug is 80 l and 3 l /hr. The half life of the drug is/hr. The half life of the drug is

A. 0.03A. 0.03 B. 14 hrsB. 14 hrs C. 18 hrsC. 18 hrs D. 139 hrs D. 139 hrs

B. 0.693 vd (80) 18B. 0.693 vd (80) 18 Cl (3) Cl (3)

4. A 32-year-old hollywood star complains of 4. A 32-year-old hollywood star complains of weakness and blurred vision. He notes that these weakness and blurred vision. He notes that these symptoms are typically worsened with effort and symptoms are typically worsened with effort and improve with rest. Physical examination is improve with rest. Physical examination is remarkable for ptosis and weakness of limb remarkable for ptosis and weakness of limb muscles on repetitive testing.muscles on repetitive testing.

What is the mechanism of action of the agent What is the mechanism of action of the agent that is commonly prescribed for the long-term that is commonly prescribed for the long-term amelioration of these symptoms?amelioration of these symptoms?

A. Carbamylation of acetylcholinesteraseA. Carbamylation of acetylcholinesterase B. Competitive inhibition of acetylcholinesteraseB. Competitive inhibition of acetylcholinesterase C. Dephosphorylation of acetylcholinesteraseC. Dephosphorylation of acetylcholinesterase D. Direct muscarinic receptor agonistD. Direct muscarinic receptor agonist E. Direct muscarinic receptor antagonistE. Direct muscarinic receptor antagonist F. Direct nicotinic receptor agonistF. Direct nicotinic receptor agonist G. Direct nicotinic receptor antagonistG. Direct nicotinic receptor antagonist H. Phosphorylation of acetylcholinesteraseH. Phosphorylation of acetylcholinesterase

5. A new antifungal medication is being tested 5. A new antifungal medication is being tested in Phase I clinical trials. Examination of the in Phase I clinical trials. Examination of the pharmacokinetic properties of the drug reveals pharmacokinetic properties of the drug reveals that the half-life of the drug is 3 hours. If a that the half-life of the drug is 3 hours. If a continuous intravenous infusion of this drug continuous intravenous infusion of this drug were started on a research subject, how long were started on a research subject, how long would it take to reach 75% of steady statewould it take to reach 75% of steady state??

A. 3 hoursA. 3 hours B. 6 hoursB. 6 hours C. 9 hoursC. 9 hours D. 12 hoursD. 12 hours E. 18 hoursE. 18 hours

The correct answer is B. The rule of The correct answer is B. The rule of thumb is that the plasma concentration thumb is that the plasma concentration will reach 50% in one half-life, 75% in will reach 50% in one half-life, 75% in two half-lives, 87.5% in three half-lives, two half-lives, 87.5% in three half-lives, etc., so that the difference between the etc., so that the difference between the current drug level and 100% halves with current drug level and 100% halves with each half-life. In this instance, it takes each half-life. In this instance, it takes two half-lives to reach 75%. The half-live two half-lives to reach 75%. The half-live of this drug is 3 hours, so two half-lives is of this drug is 3 hours, so two half-lives is 6 hours. 6 hours.

6. 6. A 15-year-old boy presents to the A 15-year-old boy presents to the emergency room with agitation, emergency room with agitation, mydriasis, and hot, dry skin. Physical mydriasis, and hot, dry skin. Physical examination reveals decreased bowel examination reveals decreased bowel sounds and tachycardia. Assuming that sounds and tachycardia. Assuming that he is suffering from a drug overdose, he is suffering from a drug overdose, which class of drugs is most likely which class of drugs is most likely responsible for his symptoms?responsible for his symptoms?

A. AnticholinergicA. Anticholinergic B. CholinomimeticB. Cholinomimetic C. OpioidC. Opioid D. SalicylateD. Salicylate E. Sedative-hypnoticE. Sedative-hypnotic

7. After a single dose of a drug 7. After a single dose of a drug which has a half-life of 12 hours, which has a half-life of 12 hours, what percentage of the dose is what percentage of the dose is still in the body after 1 day?still in the body after 1 day?

A. 87.5%A. 87.5% B. 75%B. 75% C. 50%C. 50% D. 25%D. 25%

9. A 24-year-old farm worker is rushed to a 9. A 24-year-old farm worker is rushed to a nearby emergency room after an accidental nearby emergency room after an accidental exposure to parathion. He is in respiratory exposure to parathion. He is in respiratory distress and is bradycardic. Which of the distress and is bradycardic. Which of the following drugs can be given to increase following drugs can be given to increase the activity of his acetylcholinesterase?the activity of his acetylcholinesterase?

A. AtropineA. AtropineB. DeferoxamineB. DeferoxamineC. DimercaprolC. DimercaprolD. N-acetylcysteineD. N-acetylcysteineE. PhysostigmineE. PhysostigmineF. PralidoximeF. Pralidoxime

Pralidoxime (2-PAM) 2-pyridine aldoxime Pralidoxime (2-PAM) 2-pyridine aldoxime methiodidemethiodide is an acetylcholinesterase (AChE) is an acetylcholinesterase (AChE) reactivating agent. It is only useful for reactivating agent. It is only useful for counteracting AChE inhibitors which act bycounteracting AChE inhibitors which act by

phosphorylating the enzyme phosphorylating the enzyme (organophosphates). Pralidoxime can remove (organophosphates). Pralidoxime can remove the phosphate group from AChE, thus the phosphate group from AChE, thus regenerating the enzyme. regenerating the enzyme.

This must be done in a timely fashion because This must be done in a timely fashion because normally after the phosphate group is bound normally after the phosphate group is bound to the enzyme, it undergoes a chemical to the enzyme, it undergoes a chemical reaction known as "aging." Once this bond reaction known as "aging." Once this bond ages, pralidoxime will no longer be effective.ages, pralidoxime will no longer be effective.