Katzung Board Review with complete
Solution (Latest update)
INTRODUCTION
1. A 3-year-old is brought to the emergency department
having just ingested a large overdose of tolbutamide, an oral
antidiabetic drug. Tolbutamide is a weak acid with a pKa
of 5.3. It is capable of entering most tissues, including the
brain. On physical examination, the heart rate is 100/min,
blood pressure 90/50 mm Hg, and respiratory rate
20/min.
Which of the following statements about this case of tolbutamide
overdose is most correct?
(A) Urinary excretion would be accelerated by
administration of NH4Cl, an acidifying agent
(B) Urinary excretion would be accelerated by
giving NaHCO3, an alkalinizing agent
(C) Less of the drug would be ionized at blood pH than
at stomach pH
(D) Absorption of the drug would be slower from the
stomach than from the small intestine
(E) Hemodialysis is the only effective therapy
2. Botulinum toxin is a large protein molecule. Its action on
cholinergic transmission depends on an intracellular action
within nerve endings. Which one of the following processes
is best suited for permeation of very large protein
molecules into cells?
(A) Aqueous diffusion
(B) Endocytosis
(C) First-pass effect
(D) Lipid diffusion
(E) Special carrier transport
3. A 12-year-old child has bacterial pharyngitis and is to receive
an oral antibiotic. She complains of a sore throat and pain on
swallowing. The tympanic membranes are slightly reddened
bilaterally, but she does not complain of earache. Blood
pressure
,is 105/70 mm Hg, heart rate 100/mm, temperature
37.8 C (100.1 F). Ampicillin is a weak organic acid with
a pKa of 2.5. What percentage of a given dose will be in the
lipid-soluble form in the duodenum at a pH of 4.5?
(A) About 1%
(B) About 10%
(C) About 50%
(D) About 90%
(E) About 99%
4. Ampicillin is eliminated by first-order kinetics. Which of the
following statements best describes the process by which
the plasma concentration of this drug declines?
(A) There is only 1 metabolic path for drug elimination
(B) The half-life is the same regardless of the
plasma concentration
(C) The drug is largely metabolized in the liver after
oral administration and has low bioavailability
(D) The rate of elimination is proportional to the rate of
administration at all times
(E) The drug is distributed to only 1 compartment outside
the vascular system
5. The pharmacokinetics of a new drug are under study in
a phase 1 clinical trial. Which statement about the
distribution of drugs to specific tissues is most correct?
(A) Distribution to an organ is independent of blood flow
(B) Distribution is independent of the solubility of the drug
in that tissue
(C) Distribution into a tissue depends on the unbound
drug concentration gradient between blood and the tissue
(D) Distribution is increased for drugs that are
strongly bound to plasma proteins
(E) Distribution has no effect on the half-life of the drug
6. The pharmacokinetic process or property that
distinguishes the elimination of ethanol and high doses of
phenytoin and aspirin from the elimination of most other
drugs is called
(A) Distribution
,(B) Excretion
(C) First-pass effect
(D) First-order elimination
(E) Zero-order elimination
7. A new drug was administered intravenously, and its plasma
levels were measured for several hours. A graph was prepared
as shown below, with the plasma levels plotted on a
logarithmic ordinate and time on a linear abscissa. It was
concluded
that the drug has first-order kinetics. From this graph, what
is the best estimate of the half-life?
(A) 0.5 h
(B) 1 h
(C) 3 h
(D) 4 h
(E) 7 h
8. A large pharmaceutical company has conducted
extensive animal testing of a new drug for the treatment of
advanced prostate cancer. The chief of research and
development recommends
that the company now submit an IND application
in order to start clinical trials. Which of the following statements
is most correct regarding clinical trials of new drugs?
(A) Phase 1 involves the study of a small number of
normal volunteers by highly trained clinical
pharmacologists
(B) Phase 2 involves the use of the new drug in a
large number of patients (1000–5000) who have the
disease to be treated under conditions of proposed
use (eg, outpatients)
(C) Chronic animal toxicity studies must be complete
and reported in the IND
(D) Phase 4 involves the detailed study of toxic effects
that have been discovered in phase 3
(E) Phase 2 requires the use of a positive control (a
known effective drug) and a placebo
, 9. Which of the following statements about animal testing of
potential new therapeutic agents is most correct?
(A) Extends at least 3 years to discover late toxicities
(B) Requires at least 1 primate species (eg, rhesus monkey)
(C) Requires the submission of histopathologic slides
and specimens to the FDA for evaluation by government
scientists
(D) Has good predictability for drug allergy-type reactions
(E) May be abbreviated in the case of some very toxic agent
10. The “dominant lethal” test involves the treatment of a male
adult animal with a chemical before mating; the pregnant
female is later examined for fetal death and abnormalities.
The dominant lethal test therefore is a test of
(A) Teratogenicity
(B) Mutagenicity
(C) Carcinogenicity
(D) Sperm viability
11. Which of the following would probably not be included in
an optimal phase 3 clinical trial of a new analgesic drug for
mild pain?
(A) A negative control (placebo)
(B) A positive control (current standard analgesic therapy)
(C) Double-blind protocol (in which neither the patient nor
immediate observers of the patient know which agent is
active)
(D) A group of 1000–5000 subjects with a clinical condition
requiring analgesia
(E) Prior submission of an NDA (new drug application)
to the FDA
12. Which of the following statements about the testing of new
compounds for potential therapeutic use in the treatment of
hypertension is most correct?
(A) Animal tests cannot be used to predict the types of
clinical toxicities that may occur because there is no
correlation
with human toxicity
(B) Human studies in normal individuals will be done
before the drug is used in individuals with
hypertension
Solution (Latest update)
INTRODUCTION
1. A 3-year-old is brought to the emergency department
having just ingested a large overdose of tolbutamide, an oral
antidiabetic drug. Tolbutamide is a weak acid with a pKa
of 5.3. It is capable of entering most tissues, including the
brain. On physical examination, the heart rate is 100/min,
blood pressure 90/50 mm Hg, and respiratory rate
20/min.
Which of the following statements about this case of tolbutamide
overdose is most correct?
(A) Urinary excretion would be accelerated by
administration of NH4Cl, an acidifying agent
(B) Urinary excretion would be accelerated by
giving NaHCO3, an alkalinizing agent
(C) Less of the drug would be ionized at blood pH than
at stomach pH
(D) Absorption of the drug would be slower from the
stomach than from the small intestine
(E) Hemodialysis is the only effective therapy
2. Botulinum toxin is a large protein molecule. Its action on
cholinergic transmission depends on an intracellular action
within nerve endings. Which one of the following processes
is best suited for permeation of very large protein
molecules into cells?
(A) Aqueous diffusion
(B) Endocytosis
(C) First-pass effect
(D) Lipid diffusion
(E) Special carrier transport
3. A 12-year-old child has bacterial pharyngitis and is to receive
an oral antibiotic. She complains of a sore throat and pain on
swallowing. The tympanic membranes are slightly reddened
bilaterally, but she does not complain of earache. Blood
pressure
,is 105/70 mm Hg, heart rate 100/mm, temperature
37.8 C (100.1 F). Ampicillin is a weak organic acid with
a pKa of 2.5. What percentage of a given dose will be in the
lipid-soluble form in the duodenum at a pH of 4.5?
(A) About 1%
(B) About 10%
(C) About 50%
(D) About 90%
(E) About 99%
4. Ampicillin is eliminated by first-order kinetics. Which of the
following statements best describes the process by which
the plasma concentration of this drug declines?
(A) There is only 1 metabolic path for drug elimination
(B) The half-life is the same regardless of the
plasma concentration
(C) The drug is largely metabolized in the liver after
oral administration and has low bioavailability
(D) The rate of elimination is proportional to the rate of
administration at all times
(E) The drug is distributed to only 1 compartment outside
the vascular system
5. The pharmacokinetics of a new drug are under study in
a phase 1 clinical trial. Which statement about the
distribution of drugs to specific tissues is most correct?
(A) Distribution to an organ is independent of blood flow
(B) Distribution is independent of the solubility of the drug
in that tissue
(C) Distribution into a tissue depends on the unbound
drug concentration gradient between blood and the tissue
(D) Distribution is increased for drugs that are
strongly bound to plasma proteins
(E) Distribution has no effect on the half-life of the drug
6. The pharmacokinetic process or property that
distinguishes the elimination of ethanol and high doses of
phenytoin and aspirin from the elimination of most other
drugs is called
(A) Distribution
,(B) Excretion
(C) First-pass effect
(D) First-order elimination
(E) Zero-order elimination
7. A new drug was administered intravenously, and its plasma
levels were measured for several hours. A graph was prepared
as shown below, with the plasma levels plotted on a
logarithmic ordinate and time on a linear abscissa. It was
concluded
that the drug has first-order kinetics. From this graph, what
is the best estimate of the half-life?
(A) 0.5 h
(B) 1 h
(C) 3 h
(D) 4 h
(E) 7 h
8. A large pharmaceutical company has conducted
extensive animal testing of a new drug for the treatment of
advanced prostate cancer. The chief of research and
development recommends
that the company now submit an IND application
in order to start clinical trials. Which of the following statements
is most correct regarding clinical trials of new drugs?
(A) Phase 1 involves the study of a small number of
normal volunteers by highly trained clinical
pharmacologists
(B) Phase 2 involves the use of the new drug in a
large number of patients (1000–5000) who have the
disease to be treated under conditions of proposed
use (eg, outpatients)
(C) Chronic animal toxicity studies must be complete
and reported in the IND
(D) Phase 4 involves the detailed study of toxic effects
that have been discovered in phase 3
(E) Phase 2 requires the use of a positive control (a
known effective drug) and a placebo
, 9. Which of the following statements about animal testing of
potential new therapeutic agents is most correct?
(A) Extends at least 3 years to discover late toxicities
(B) Requires at least 1 primate species (eg, rhesus monkey)
(C) Requires the submission of histopathologic slides
and specimens to the FDA for evaluation by government
scientists
(D) Has good predictability for drug allergy-type reactions
(E) May be abbreviated in the case of some very toxic agent
10. The “dominant lethal” test involves the treatment of a male
adult animal with a chemical before mating; the pregnant
female is later examined for fetal death and abnormalities.
The dominant lethal test therefore is a test of
(A) Teratogenicity
(B) Mutagenicity
(C) Carcinogenicity
(D) Sperm viability
11. Which of the following would probably not be included in
an optimal phase 3 clinical trial of a new analgesic drug for
mild pain?
(A) A negative control (placebo)
(B) A positive control (current standard analgesic therapy)
(C) Double-blind protocol (in which neither the patient nor
immediate observers of the patient know which agent is
active)
(D) A group of 1000–5000 subjects with a clinical condition
requiring analgesia
(E) Prior submission of an NDA (new drug application)
to the FDA
12. Which of the following statements about the testing of new
compounds for potential therapeutic use in the treatment of
hypertension is most correct?
(A) Animal tests cannot be used to predict the types of
clinical toxicities that may occur because there is no
correlation
with human toxicity
(B) Human studies in normal individuals will be done
before the drug is used in individuals with
hypertension
