Transcript USMLE I (2).

USMLE
I
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1. The pharmacokinetic properties of a new
antihistamine are being studied in normal
volunteers during phase I clinical trials. The
clearance and half-life of the drug are
determined to be 4.0 L/hour and 10 hours,
respectively. Which of the following values is
the approximate volume of distribution for this
drug?
A. 0.06 L
B. 14 L
C. 45 L
D. 60 L
E. 130 L
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The correct answer is D. The volume of
distribution of a drug can be determined
using the following equation:
t1/2 = (0.693 x Vd)/CL
Therefore, 10 hours = (0.693 x Vd)/(4.0
L/hour),
40 hours = 0.693 x Vd,
Vd = 58 L which is approximately 60 L
2. A cardiovascular pharmacologist is researching
the effects of new compounds on arteriolar
resistance. Drug X maximally increases vascular
resistance by 50% at a dose of 20 mg/mL. Drug Y
maximally increases vascular resistance by 75% at a
dose of 40 mg/mL. Which of the following
conclusions can the researcher draw from this
experiment?
A. Drug X has a smaller volume of distribution than
Drug Y
B. Drug X has a shorter half-life than Drug Y
C. Drug X is less efficacious than Drug Y
D. Drug X is less potent than Drug Y
E. Drug X has a lower LD50 than Drug Y
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The correct answer is C. The only conclusion that
can be drawn from this data is that Drug X is less
efficacious than Drug Y. Efficacy is defined as the
maximum effect that can be produced by a drug,
regardless of dose. Drug X can only produce a
50% change in resistance, whereas Drug Y can
produce a 75% change in resistance. Therefore,
Drug X is less efficacious than Drug Y.
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3.The pharmacokinetic properties of a new
drug are being studied under phase 1
clinical trials. The vol of distribution and
clearance of the drug is 80 l and 3 l /hr.
The half life of the drug is
A. 0.03
B. 14 hrs
C. 18 hrs
D. 139 hrs
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B.
0.693
vd (80)
Cl (3)
18
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4. A migrant worker presents to the emergency
room in respiratory distress. He had been spraying
parathion in the fields for several days, and today
he began to feel sweaty and dizzy. By the time he
got to the hospital he was drooling, gasping, and
becoming agitated. These symptoms are due to the
actions of parathion on which of the following?
A. Acetylcholinesterase
B. Muscarinic receptors
C. Neuronal lipid bilayer
D. Nicotinic receptors
E. Voltage-gated sodium channels
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The correct answer is A. Organophosphate
insecticides such as parathion function as
acetylcholinesterase inhibitors, producing
increased acetylcholine levels at all
cholinergic synapses. Although both
muscarinic and nicotinic receptors are
stimulated, the muscarinic effects are
usually identified first. Treatment with
atropine is generally indicated with
organophosphate intoxication.
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5. A 32-year-old hollywood star complains of weakness
and blurred vision. He notes that these symptoms are
typically worsened with effort and improve with rest.
Physical examination is remarkable for ptosis and
weakness of limb muscles on repetitive testing.
What is the mechanism of action of the agent that is
commonly prescribed for the long-term amelioration of
these symptoms?
A. Carbamylation of acetylcholinesterase
B. Competitive inhibition of acetylcholinesterase
C. Dephosphorylation of acetylcholinesterase
D. Direct muscarinic receptor agonist
E. Direct muscarinic receptor antagonist
F. Direct nicotinic receptor agonist
G. Direct nicotinic receptor antagonist
H. Phosphorylation of acetylcholinesterase
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6. A new antifungal medication is being
tested in Phase I clinical trials. Examination of
the pharmacokinetic properties of the drug
reveals that the half-life of the drug is 3
hours. If a continuous intravenous infusion of
this drug were started on a research subject,
how long would it take to reach 75% of
steady state?
A. 3 hours
B. 6 hours
C. 9 hours
D. 12 hours
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The correct answer is B. The rule of
thumb is that the plasma
concentration will reach 50% in one
half-life, 75% in two half-lives, 87.5%
in three half-lives, etc., so that the
difference between the current drug
level and 100% halves with each halflife. In this instance, it takes two halflives to reach 75%. The half-live of
this drug is 3 hours, so two half-lives
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7. A 15-year-old boy presents to the
emergency room with agitation,
mydriasis, and hot, dry skin. Physical
examination reveals decreased bowel
sounds and tachycardia. Assuming that
he is suffering from a drug overdose,
which class of drugs is most likely
responsible for his symptoms?
A. Anticholinergic
B. Cholinomimetic
C. Opioid
D. Salicylate
E. Sedative-hypnotic
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8. After a single dose of a drug which
has a half-life of 12 hours, what
percentage of the
dose is still in
the body after 1 day?
A. 87.5%
B. 75%
C. 50%
D. 25%
9. A 24-year-old farm worker is rushed to a
nearby emergency room after an accidental
exposure to parathion. He is in respiratory
distress and is bradycardic. Which of the
following drugs can be given to increase the
activity of his acetylcholinesterase?
A. Atropine
B. Deferoxamine
C. Dimercaprol
D. N-acetylcysteine
E. Physostigmine
F. Pralidoxime
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Pralidoxime (2-PAM) 2-pyridine aldoxime methiodide
is an acetylcholinesterase (AChE) reactivating agent.
It is only useful for counteracting AChE inhibitors
which act by
phosphorylating the enzyme (organophosphates).
Pralidoxime can remove the phosphate group from
AChE, thus regenerating the enzyme.
This must be done in a timely fashion because
normally after the phosphate group is bound to the
enzyme, it undergoes a chemical reaction known as
"aging." Once this bond ages, pralidoxime will no
longer be effective.