,Chapter 1 – Principles of Pharmacology
Focus:
Basics of how drugs interact with the body (pharmacokinetics) and how the body
affects drugs (absorption, distribution, metabolism, excretion).
Key Concepts:
Drug administration routes
Blood-brain barrier
Dose-response relationships
Half-life and bioavailability
1.
A researcher is developing a drug intended to treat central nervous system
disorders. Which of the following molecular properties would most enhance the
drug’s ability to cross the blood-brain barrier?
A. High molecular weight and hydrophilicity
B. Low molecular weight and lipophilicity
C. High protein binding in plasma
D. Ionization at physiological pH
✅ Correct Answer: B
Rationale:
The blood-brain barrier (BBB) selectively allows passage of small, lipophilic (fat-
soluble) molecules by passive diffusion. Hydrophilic, large, or ionized molecules
have limited CNS penetration unless transported actively. Therefore, low
molecular weight and lipophilicity are essential for CNS drug delivery.
2.
Which of the following best describes first-pass metabolism?
,A. The initial binding of a drug to plasma proteins in circulation
B. The enzymatic degradation of a drug in the liver before it reaches systemic
circulation
C. The renal excretion of drugs before they are absorbed
D. The immediate inactivation of a drug by target tissue receptors
✅ Correct Answer: B
Rationale:
First-pass metabolism refers to the pre-systemic degradation of orally
administered drugs by liver enzymes (mainly in the hepatic portal system) before
they enter the general circulation. This reduces bioavailability and is a key
consideration in drug design.
3.
A clinician prescribes two drugs that are both metabolized by CYP3A4 enzymes.
What is the most likely pharmacokinetic consequence?
A. Enhanced renal clearance of both drugs
B. Reduced absorption due to transporter competition
C. Possible drug-drug interactions due to metabolic pathway saturation
D. Increased bioavailability via first-pass activation
✅ Correct Answer: C
Rationale:
Drugs metabolized by the same cytochrome P450 enzymes may compete, leading
to enzyme saturation or inhibition, altering plasma levels. This can result in drug-
drug interactions, toxicity, or reduced efficacy.
4.
A dose-response curve plateaus even when increasing drug doses are
administered. What is the most likely explanation?
, A. All available receptors are occupied (receptor saturation).
B. The drug has become ionized at higher doses.
C. The drug’s half-life has decreased at higher doses.
D. Renal excretion has stopped responding to dose changes.
✅ Correct Answer: A
Rationale:
At maximal effect, all receptors are occupied (saturation), so further dose
increases do not increase efficacy. This reflects the ceiling of the dose-response
relationship.
5.
Why might intravenous (IV) administration of a drug produce a faster onset of
action than oral administration?
A. IV administration bypasses the gastrointestinal tract and first-pass metabolism.
B. IV drugs are less likely to bind to plasma proteins.
C. Oral drugs are more lipid-soluble, delaying action.
D. IV drugs are not subject to enzymatic degradation in the blood.
✅ Correct Answer: A
Rationale:
IV administration provides direct entry into systemic circulation, bypassing
absorption barriers and avoiding first-pass metabolism, resulting in a faster onset
of action compared to oral routes.
6.
A drug has a half-life of 6 hours. After 24 hours, approximately what percentage
of the original drug remains in plasma?
A. 50%
B. 25%
Focus:
Basics of how drugs interact with the body (pharmacokinetics) and how the body
affects drugs (absorption, distribution, metabolism, excretion).
Key Concepts:
Drug administration routes
Blood-brain barrier
Dose-response relationships
Half-life and bioavailability
1.
A researcher is developing a drug intended to treat central nervous system
disorders. Which of the following molecular properties would most enhance the
drug’s ability to cross the blood-brain barrier?
A. High molecular weight and hydrophilicity
B. Low molecular weight and lipophilicity
C. High protein binding in plasma
D. Ionization at physiological pH
✅ Correct Answer: B
Rationale:
The blood-brain barrier (BBB) selectively allows passage of small, lipophilic (fat-
soluble) molecules by passive diffusion. Hydrophilic, large, or ionized molecules
have limited CNS penetration unless transported actively. Therefore, low
molecular weight and lipophilicity are essential for CNS drug delivery.
2.
Which of the following best describes first-pass metabolism?
,A. The initial binding of a drug to plasma proteins in circulation
B. The enzymatic degradation of a drug in the liver before it reaches systemic
circulation
C. The renal excretion of drugs before they are absorbed
D. The immediate inactivation of a drug by target tissue receptors
✅ Correct Answer: B
Rationale:
First-pass metabolism refers to the pre-systemic degradation of orally
administered drugs by liver enzymes (mainly in the hepatic portal system) before
they enter the general circulation. This reduces bioavailability and is a key
consideration in drug design.
3.
A clinician prescribes two drugs that are both metabolized by CYP3A4 enzymes.
What is the most likely pharmacokinetic consequence?
A. Enhanced renal clearance of both drugs
B. Reduced absorption due to transporter competition
C. Possible drug-drug interactions due to metabolic pathway saturation
D. Increased bioavailability via first-pass activation
✅ Correct Answer: C
Rationale:
Drugs metabolized by the same cytochrome P450 enzymes may compete, leading
to enzyme saturation or inhibition, altering plasma levels. This can result in drug-
drug interactions, toxicity, or reduced efficacy.
4.
A dose-response curve plateaus even when increasing drug doses are
administered. What is the most likely explanation?
, A. All available receptors are occupied (receptor saturation).
B. The drug has become ionized at higher doses.
C. The drug’s half-life has decreased at higher doses.
D. Renal excretion has stopped responding to dose changes.
✅ Correct Answer: A
Rationale:
At maximal effect, all receptors are occupied (saturation), so further dose
increases do not increase efficacy. This reflects the ceiling of the dose-response
relationship.
5.
Why might intravenous (IV) administration of a drug produce a faster onset of
action than oral administration?
A. IV administration bypasses the gastrointestinal tract and first-pass metabolism.
B. IV drugs are less likely to bind to plasma proteins.
C. Oral drugs are more lipid-soluble, delaying action.
D. IV drugs are not subject to enzymatic degradation in the blood.
✅ Correct Answer: A
Rationale:
IV administration provides direct entry into systemic circulation, bypassing
absorption barriers and avoiding first-pass metabolism, resulting in a faster onset
of action compared to oral routes.
6.
A drug has a half-life of 6 hours. After 24 hours, approximately what percentage
of the original drug remains in plasma?
A. 50%
B. 25%
