LE1 (2024) Flashcards
What does Pharmacokinetics include?
A. Complication in drug therapy
B. Drug biotransformation in the organism
C. Influence of drugs on metabolism processes
D. Influence of drugs on genes
B. Drug biotransformation in the organism
Rationale: Pharmacokinetics involves the study of how drugs are absorbed, distributed, metabolized (biotransformation), and excreted by the body.
The volume of distribution relates to:
A. An uncharged drug reaching the systemic circulation
B. Single to a daily dose of an administrated drug
C. An administrated dose to a body weight
D. The amount of a drug in the body to the concentration of a drug in plasma
D. The amount of a drug in the body to the concentration of a drug in plasma
Rationale: The volume of distribution (Vd) is a theoretical volume that relates the amount of drug in the body to its concentration in the blood or plasma.
Innovated the use of the double-blind design for clinical trials and the use of effect kinetics to measure the absolute bioavailability of digoxin:
A. Rudolph Bucheim
B. Harry Gold and McKeen Cattell
C. Harry Gold and Walter Modell
D. Paul Martini
C. Harry Gold and Walter Modell
Rationale: Harry Gold and Walter Modell are credited with innovations in clinical trial designs and methodologies for measuring drug bioavailability, including digoxin.
The main goal of Clinical Pharmacology is concerned with:
A. The safety and efficacy of currently available drugs
B. Development of new and improved pharmacotherapy
C. Define the basis for variability in therapeutic and toxic responses to medicine
D. All of the above
D. All of the above
Rationale: Clinical Pharmacology aims to ensure the safety and efficacy of drugs, develop new pharmacotherapies, and understand the variability in drug responses.
For the calculation of the volume of distribution (Vd) one must take into account:
A. Concentration of a substance in plasma
B. Concentration of substance in urine
C. Therapeutical width of drug action
D. Daily dose of drug
A. Concentration of a substance in plasma
Rationale: The volume of distribution is calculated using the amount of drug in the body divided by the concentration of the drug in the plasma.
Based on the previous clinical pharmacological studies conducted, this graph illustrates:
A. Variability in Drug Exposure
B. Inter-individual Variation in Drug Exposure
C. Defining therapeutic range of concentrations
D. Determining Volume of distribution
B. Inter-individual Variation in Drug Exposure
Rationale: The graph shows the plasma concentration of nortriptyline over time in individuals with different numbers of functional CYP2D6 genes. CYP2D6 is an enzyme involved in the metabolism of nortriptyline, and the number of functional genes affects how quickly the drug is metabolized. The variability in plasma concentration among individuals with different gene numbers highlights inter-individual variation in drug exposure.
In order to estimate the maintenance dose, we need to understand the concept of:
A. Half-life and Clearance
B. Bioavailability and Volume of Distribution
C. Absorption Rate and Protein Binding
D. Elimination Rate and Peak Plasma Concentration
A. Half-life and Clearance
Rationale: The maintenance dose of a drug is calculated based on its half-life and clearance to maintain a steady-state concentration in the plasma.
Target proteins which a drug molecule binds to:
A. Only receptor
B. Only ion channel
C. Only carriers
D. All of the above (AOTA)
D. All of the above (AOTA)
Rationale: Drugs can bind to receptors, ion channels, carriers, and other proteins, influencing their function.
If an agonist can produce maximal effects and has high efficacy, it’s called:
A. Partial agonist
B. Antagonist
C. Agonist-antagonist
D. Full agonist
D. Full agonist
Rationale: A full agonist can produce the maximal response by fully activating the receptor.
If an agonist can produce submaximal effects and has moderate efficacy, it’s called:
A. Partial agonist
B. Antagonist
C. Agonist-antagonist
D. Full agonist
A. Partial agonist
Rationale: A partial agonist produces a weaker, or less efficacious, response than a full agonist even when binding to the same receptor.
A competitive antagonist is a substance that:
A. Interacts with receptors and produces submaximal effect
B. Binds to the same receptor site and progressively inhibits the agonist response
C. Binds to the nonspecific sites of tissue
D. Binds to one receptor subtype as an agonist and to another as an antagonist
B. Binds to the same receptor site and progressively inhibits the agonist response
Rationale: A competitive antagonist competes with the agonist for the same binding site on the receptor, reducing the effect of the agonist.
What phenomenon can occur in case of using a combination of drugs?
A. Tolerance
B. Tachyphylaxis
C. Accumulation
D. Synergism
D. Synergism
Rationale: Synergism occurs when the combined effect of two drugs is greater than the sum of their individual effects.
Tolerance or desensitization is characterized by the following EXCEPT:
A. Decreased response to the same dose with repeated exposure
B. Sometimes occurs in an acute dose (e.g., alcohol)
C. Dose-response curve shift to the left
D. Caused by compensatory mechanisms that oppose the effects of the drug
C. Dose-response curve shift to the left
Rationale: Tolerance typically results in a rightward shift of the dose-response curve, meaning higher doses are needed to achieve the same effect.
It is possible to develop tolerance to some side effects and sensitization to other side effects of the same drug.
True or False?
True
Rationale: Tolerance and sensitization can occur simultaneously to different effects of the same drug.
The condition in which the repeated administration of a drug may produce effects that are more pronounced than those produced by the first dose:
A. Cumulative
B. Additive
C. Synergistic
D. Antagonistic
A. Cumulative
Rationale: Cumulative effects occur when the effects of a drug increase with repeated administration due to accumulation in the body.
Rate of elimination is independent of drug administration:
A. First Order Kinetics
B. Zero Order Kinetics
C. Biotransformation
D. Half-life
B. Zero Order Kinetics
Rationale: In zero-order kinetics, the rate of drug elimination is constant and independent of the drug concentration.
Based on this study conducted by Gold et al, it can be concluded that:
A. Significant reduction in heart rate after IV administration of digoxin with instantaneous effect
B. The rate of distribution may impact the onset of drug action
C. Distribution does not delay the onset of digoxin
D. All of the above
B. The rate of distribution may impact the onset of drug action
Rationale: The graph shows that the onset of digoxin’s effect on ventricular rate differs between oral and intravenous administration, indicating that the distribution phase affects the onset of action. The intravenous route shows a faster decrease in heart rate compared to the oral route, suggesting that distribution plays a role in how quickly the drug starts to work.
This study conducted in Boston by Dr. Smith et al. among patients with CHF treated with digoxin can address our concern in:
A. Defining therapeutic range of concentrations
B. Applying target concentration strategy
C. Determining the loading dose
D. Therapeutic drug monitoring
A. Defining therapeutic range of concentrations
Rationale: Studies on digoxin, particularly in patients with CHF, are often aimed at establishing the therapeutic range of concentrations that are effective and safe.
Drugs that are candidates for TDM (Therapeutic Drug Monitoring) EXCEPT:
A. High Therapeutic Index
B. No physiologic endpoints or biomarkers to guide dosage
C. Need to monitor adherence
D. Pharmacokinetics vary widely between individuals
A. High Therapeutic Index
Rationale: Drugs with a high therapeutic index generally do not require TDM because they are less likely to cause toxicity at therapeutic doses.
Potential outcomes of pharmacogenetic research include all the following EXCEPT:
A. Lower incidence of adverse drug effects
B. New drug development
C. Higher health care costs
D. Improved treatment outcomes
E. Pretreatment screening for genetic polymorphisms
C. Higher health care costs
Rationale: Pharmacogenetic research is aimed at improving drug efficacy and safety, potentially lowering health care costs by reducing adverse effects and ineffective treatments.
The most commonly occurring variant in the human genome is:
A. Tandem-repeat polymorphism
B. Premature stop codon
C. Nucleotide base insertion
D. Single-nucleotide polymorphism
E. Defective gene splicing
D. Single-nucleotide polymorphism
Rationale: Single-nucleotide polymorphisms (SNPs) are the most frequent type of genetic variation in the human genome.
Genetic variations in drug targets may contribute to which drug property?
A. Bioavailability
B. Half-life
C. Racial differences in response
D. Peak-dose area under the curve
E. Entry into the central nervous system
C. Racial differences in response
Rationale: Genetic variations in drug targets can lead to differences in drug responses among different racial groups due to variations in the genetic makeup that influence drug efficacy and safety.
The CYP isozyme that metabolizes Plavix:
A. CYP2D6
B. CYP2E1
C. CYP2C19
D. CYP3A4
C. CYP2C19
Rationale: CYP2C19 is the primary enzyme responsible for the metabolism of clopidogrel (Plavix) into its active form.
Genetic analysis permits:
A. More rapid determination of stable therapeutic dose
B. Better prediction of dose than clinical methods alone
C. Applicable to 70-75% of patients not in controlled anticoagulation centers
D. All of the above
D. All of the above
Rationale: Genetic analysis can lead to more rapid determination of stable therapeutic doses, better prediction of doses than clinical methods alone, and is applicable to a significant portion of patients not in controlled anticoagulation centers.
Pharmacogenetic testing may be used to:
A. Find out whether a certain medicine could be effective for you
B. Find out what the best dosage might be for you
C. Predict whether you will have a serious side effect from a medicine
D. All of the above
D. All of the above
Rationale: Pharmacogenetic testing can help determine the effectiveness of a medicine, the best dosage, and predict potential serious side effects.
When counseling a patient about their pharmacogenetic test results the following statement is most acceptable to use:
A. Your DNA is mutated
B. Your DNA is abnormal
C. You have a genetic variation or polymorphism
D. All of the above
C. You have a genetic variation or polymorphism
Rationale: Using the term “genetic variation or polymorphism” is accurate and avoids negative connotations associated with “mutation” or “abnormal.”
Effect on metabolism for an individual who took an active drug and is considered as a poor metabolizer phenotype:
A. May need lower dose
B. Will have good efficacy with rapid effect
C. Will have poor efficacy
D. May need greater dose
A. May need lower dose
Rationale: Poor metabolizers may require a lower dose of an active drug due to slower metabolism, leading to higher plasma concentrations.
The outcome of this stage of drug development will include approval and marketing:
A. Pre-clinical Pharmacology and Toxicology
B. Clinical Trials in Humans
C. Review
D. Large-Scale Clinical Use Surveillance
E. Research and Development
C. Review
Rationale: The review stage involves regulatory agencies evaluating the drug’s safety and efficacy data, leading to approval and marketing.
True regarding Treatment IND:
A. Intended to treat serious life-threatening diseases (e.g., AIDS/its complications)
B. No comparable satisfactory alternative treatment
C. Under investigation in controlled clinical trial (usually Phase II)
D. Sponsor actively pursuing marketing approval
E. All of the above
E. All of the above
Rationale: Treatment IND is intended for serious life-threatening diseases, requires no comparable satisfactory alternative treatment, is under investigation in controlled clinical trials, and the sponsor is actively pursuing marketing approval.
Involves drug metabolism and safety assessment:
A. Phase I and II
B. Phase II and III
C. Phase I, II, and III
D. Phase IV
C. Phase I, II, and III
Rationale: Drug metabolism and safety are assessed throughout Phases I, II, and III of clinical trials.
Given the information shown in the figure below, which of the following statements is correct?
A. Drug A has the most appropriate pharmacodynamic properties of the three drugs shown as it reaches maximal efficacy within the therapeutic window.
B. Drug B has the most appropriate pharmacodynamic properties of the three drugs shown as a range of its plasma concentrations are within the therapeutic window.
C. Drug C has the most appropriate pharmacodynamic properties of the three drugs shown as non-toxic effects are achieved within the therapeutic window.
D. All three drugs have appropriate pharmacodynamic properties as they all achieve maximal physiological effects and have concentrations within the therapeutic window.
B. Drug B has the most appropriate pharmacodynamic properties of the three drugs shown as a range of its plasma concentrations are within the therapeutic window.
Rationale: The therapeutic window is the range of drug plasma concentrations that produce the desired effect without causing toxicity. Drug B reaches maximal efficacy and maintains its effect within this therapeutic window, making it the most appropriate among the three drugs shown. Drug A exceeds the therapeutic window, potentially causing toxicity, while Drug C does not achieve its maximal effect within the therapeutic window.
