PDTI

She decides that she is most interested in finding out if she has any polymorphisms (SNPs) that result in changes to her proteins. What type of SNP is she MOST likely interested in?

Non-sense SNP

Non-synonymous SNP

The area under the concentration time curve is affected by how efficient the body is able to get rid of the drug.

True

The area under the concentration time curve is affected by how much drug entered the blood stream.

True

The larger the elimination rate constant of a drug eliminated by a first order process, the shorter the half-life.

True

A long half-life might allow less frequent dosing

True

For a drug eliminated by metabolism by a zero order process, enzymes responsible for elimination are likely to be saturated.

True

For a drug eliminated by metabolism through a first order process, the rate of elimination is higher at higher drug concentrations as more drug will "bump" into enzymes and more drug will be metabolized

True

In permeability-limited distribution, drugs are generally taken up much faster by highly perfused organs than less perfused organs.

False

A strong acid, whose unionized form shows a low partition coefficient, is likely to cross most membrane barriers

False

The rate with which hydrophilic compounds will move across well-built membranes will depend on the concentration gradient between free drug in plasma and free drug in tissue.

True

If two patients' volumes of distribution differ significantly (as they often do in critically ill patients) the patient with the larger Vd will show a lower initial concentration (Co) after the same dose of Drug X given by IV bolus administration.

True

Consider a patient with myocardial infarction taking a drug which binds to alpha-1-glycoprotein. The increase in plasma alpha-1-glycoprotein just after the infarction took place will result in movement of drug to plasma and a decrease in fu in plasma.

True

The rate with which a lipophilic drug of low molecular weight that is not an acid or a base is taken up by tissues will be significantly related to the blood flow through those tissues.

True

The rate with which a lipophilic drug that is not an acid or a base is taken up by brain and liver tissue is likely to be similar, as the drug will be able to cross membranes in both tissues very fast.

False

The rate at which a lipophilic drug that is not an acid or a base is taken up by fat tissue is likely to be faster than the rate at which it is taken up by the kidney

False

For a drug that shows permeability-controlled uptake into all tissues, total drug concentrations are always higher in the plasma than in tissues.

False

Permeability limited distribution is generally seen for small, lipophilic drugs.

False

Consider a lipophilic acidic drug A (pka=7, logP=5) and a lipophilic neutral drug B (logP=5). Both do not show any affinity to transporters and do not bind to tissue and plasma proteins.

Drug A will enter the brain somewhat faster

False

Consider a lipophilic acidic drug A (pka=7, logP=5) and a lipophilic neutral drug B (logP=5). Both do not show any affinity to transporters and do not bind to tissue and plasma proteins

Drug A will be unable to enter the interstitial fluid

False

Consider a lipophilic acidic drug A (pka=7, logP=5) and a lipophilic neutral drug B (logP=5). Both do not show any affinity to transporters and do not bind to tissue and plasma proteins

Drug B be is likely to have a smaller volume of distribution

False

Consider a lipophilic acidic drug A (pka=7, logP=5) and a lipophilic neutral drug B (logP=5). Both do not show any affinity to transporters and do not bind to tissue and plasma proteins

VT of drug A will be 18 L.

False

Two patients receive the low extraction drug A (lipophilic, not charged, ) which is mainly metabolized by the CYP3A4. Drug A in the absence of drug B has an extraction ratio of 0.01. It does not bind to plasma proteins. One patient also took drug B which is an enzyme inducer of CYP3A4. As a result, the intrinsic clearances between the patients differed by a factor of 2. Which of the following statements is/are correct

Differences in the total clearance observed for the two patients will be clinically

relevant

True

Two patients receive the low extraction drug A (lipophilic, not charged, ) which is mainly metabolized by the CYP3A4. Drug A in the absence of drug B has an extraction ratio of 0.01. It does not bind to plasma proteins. One patient also took drug B which is an enzyme inducer of CYP3A4. As a result, the intrinsic clearances between the patients differed by a factor of 2. Which of the following statements is/are correct

The oral bioavailability of this drug in the two patients will be different and this

difference will be of clinical relevance.

False

Two patients receive the low extraction drug A (lipophilic, not charged, ) which is mainly metabolized by the CYP3A4. Drug A in the absence of drug B has an extraction ratio of 0.01. It does not bind to plasma proteins. One patient also took drug B which is an enzyme inducer of CYP3A4. As a result, the intrinsic clearances between the patients differed by a factor of 2. Which of the following statements is/are correct

The half-life in the patient only taking drug A will be longer

True

Assume a lipophilic, protein bound drug (not an acid, not a base) that is only eliminated through renal elimination.

Decrease in plasma protein binding will result in an increase in Cl

True

Assume a lipophilic, protein bound drug (not an acid, not a base) that is only eliminated through renal elimination.

A decrease in tissue binding will result in a decrease in Cl

False

Assume a lipophilic, protein bound drug (not an acid, not a base) that is only eliminated through renal elimination.

A decrease in GFR will result in an increase in Cl

False

Assume a lipophilic, protein bound drug (not an acid, not a base) that is only eliminated through renal elimination.

A decrease in urine flow will result in a decrease in half-life

False

Creatinine is used as marker for kidney function as it probes for the activity of renal transporters

False

Creatinine itself has high plasma protein binding

False

Creatinine clearance is affected by renal disease

True

Serum creatinine plasma concentrations are affected by how much creatinine is produced by muscles.

True

Creatinine's clearance is mainly due to metabolizing enzymes.

False

Which of the following factors significantly affects the renal clearance of an unionized drug that shows complete passive renal reabsorption from the urine back into the blood?

Plasma protein binding and urine flow

A drug which is actively secreted is likely to be uncharged.

False

Active secretion is indicated when renal clearance is less than GFR*fu.

False

Clearance and volume of distribution affect each other

False

It is possible for renal clearance to be close to the kidney blood flow.

True

For all drugs that are acids or bases, the pH of the urine will affect the magnitude of renal reabsorption

False

For a multiple IV bolus regimen, if the dosing interval is the same, the shorter the half-life the more pronounced the differences between peak and trough concentrations.

True

For a multiple IV bolus regimen, the longer dosing interval, the longer it will take to achieve steady state

False

For a multiple IV bolus regimen, the accumulation degree is larger in patients with higher clearance

False

It takes more time to reach steady state for a drug with a higher degree of accumulation. (Assuming loading dose is not given, and dosing interval is the same.)

True

The shorter half-life indicates a larger Ke. Since F= eke*tau, then it will have a larger F which means more pronounced differences between peak and trough concentrations.

True

The longer dosing interval results in lower steady state concentrations hence the faster it will take to achieve steady state.

False

Patients with higher clearance have shorter half-life will show smaller accumulation degree

False

Higher accumulation means longer half-life which means time to reach steady state is longer

True

A high extraction drug was given to patient A via an intravenous (IV) bolus administration. The same dose of drug A was given to patient B via an IV bolus. Both patients show same tissue binding but Patient B shows a much higher plasma protein binding for the drug than patient A. Please assume for this problem set that: i) drug A is only cleared by hepatic clearance, ii) liver blood flow is the same for both the patients, and iii) linear pharmacokinetics.

Total AUC0-∞ for both patients will be the same

True

A high extraction drug was given to patient A via an intravenous (IV) bolus administration. The same dose of drug A was given to patient B via an IV bolus. Both patients show same tissue binding but Patient B shows a much higher plasma protein binding for the drug than patient A. Please assume for this problem set that: i) drug A is only cleared by hepatic clearance, ii) liver blood flow is the same for both the patients, and iii) linear pharmacokinetics.

Free AUC0-∞ for both patients will be the same

False

A high extraction drug was given to patient A via an intravenous (IV) bolus administration. The same dose of drug A was given to patient B via an IV bolus. Both patients show same tissue binding but Patient B shows a much higher plasma protein binding for the drug than patient A. Please assume for this problem set that: i) drug A is only cleared by hepatic clearance, ii) liver blood flow is the same for both the patients, and iii) linear pharmacokinetics.

Volume of distribution will be lower for patient B compared to patient A

True

Assuming linear kinetics, AUC0-∞ after single dose and AUC0-tau at steady-state are the same for a given drug.

True

Small doses given very frequently as intravenous bolus injections result in smaller fluctuations between peak and through plasma levels compared to large doses given less frequently.

True

Administration of a loading dose will cut the time needed to reach steady-state in half.

False

The unit for the absorption rate constant (ka) of an extended-release product is [1/h].

False

For an orally administered drug that exhibits linear pharmacokinetics, the time to reach maximum plasma concentration (tmax) is independent of dose

True

The concentration time profiles of an oral tablet will be very similar to an IV bolus injection of the same dose if the absorption is very fast and the oral bioavailability will be close to 100 %.

True

Flip-flop kinetics occurs when ka is much faster than ke

False

Drug-drug interactions due to metabolic enzyme induction can be characterized by fast onset and offset of the effect.

False

The underlying mechanism of drug-drug interactions can either have pharmacokinetic basis, pharmacodynamic basis, or both.

True

Epigenetic modifications permanently alters the DNA sequence.

False

In clinical practice, how should a prescriber try to minimize drug-drug interactions?

I. Be cautious to prescribe highly potent inducer/inhibitor.

II. Be cautious to prescribe narrow therapeutic index of victim drug.

III. When possible, choose low-risk perpetrators.

IV. Choose victim drugs with single pathway of metabolism.

I, II, and III

The term "k12" in a two compartment model represents the:

Rate constant for drug transfer from central compartment to peripheral compartment

Human transporter proteins are expressed in multiple tissues. How can transporters affect the drug disposition?

I. Elimination by renal excretion

II. Uptake into the liver

III. Absorption (uptake or efflux in the intestine)

IV. Elimination by renal excretion

V. Uptake or efflux across the placenta

VeriStrat® test results provide important information that can help make more informed treatment decisions by identifying patient groups who may receive differential treatment benefit between single-agent therapy options. This test is based on which of the following methodologies?

Proteomics

All the following alternatives are transcriptomic methods, EXCEPT:

Mass spectrometry

Which of the following statements regarding CPIC guidelines is FALSE

Concerns about genetic tests' costs and reimbursements are not a barrier for CPIC guidelines.

Which of the following is TRUE concerning the CPIC guideline for genotypes and dosing of tricyclic antidepressants (TCAs)?

They are based upon the presence of SNPs influencing pharmacokinetic parameters only

Which one of the following statements is true?

Drug targets are typically located in tissues and organs.

Which of the following factors does NOT affect the pharmacokinetic/pharmacodynamic properties of a drug?

switching to a generic version of a drug

Which one of the following statements is/are true regarding the efficacy and safety of a drug?

Pharmacokinetics and Pharmacodynamics both determine the efficacy and safety

Which one of the following is an example of the most common type of genetic polymorphism that occurs approximately every 300 bp in the human genome?

AATCGG -> AACCGG

SNP 789 is located on Chromosome 22 and is a C/T SNP. Morgan has a C at SNP 789 on one copy of Chromosome 22. Morgan also has a C at SNP 789 on the other copy of Chromosome 22. Finally, Morgan has attached ear lobes because he is homozygous CC at SNP 789 on Chromosome 22

Morgan has a C allele at SNP 789, a CC genotype at SNP 789, and an attached ear lobe phenotype

Which one of the following statements is FALSE?

Recombination can randomly occur at any point of the human genome

Assume that a drug is eliminated through a first order process. The concentration time profile will be linear when concentrations are plotted against the logarithm of time.

False

The plasma concentration time profile for a drug eliminated through a first order process is only dependent on the dose.

False

Which of the following statements concerning the area under the concentration time profile is CORRECT

For a drug eliminated through a first order process ke will decrease with increasing half-life

Dx/Dt = -Ke * X

First order process

The value of Vt is the same for all drugs (38 L).

False

For a drug that binds to a high affinity-low capacity binding protein in plasma, the fu and the volume of distribution might depend on the dose of the drug.

True

A very weak acid, whose unionized form shows a high partition coefficient, is likely to cross most membrane barriers.

True

A volume of distribution of 41 L for a lipophilic drug suggests that the drug will not bind to tissue and plasma proteins.

False

What could be possible reasons for newborns often having a smaller volume of distribution (expressed in L) for lipophilic drugs than adults. Assume for this question that plasma protein binding is the same in newborns and adults. Which statements might explain this finding?

The term Vt is smaller in newborns than in adults.

True

What could be possible reasons for newborns often having a smaller volume of distribution (expressed in L) for lipophilic drugs than adults. Assume for this question that plasma protein binding is the same in newborns and adults. Which statements might explain this finding

Transporters pumping the drug from blood into tissue are less active in newborns.

True

For a small and lipophilic drug molecule, the uptake into liver cells will be faster than the uptake into the skin

True

The rate with which hydrophilic compounds will move across well-built membranes will depend on the plasma protein binding of this drug.

True

Creatinine clearance can only be used to estimate the renal clearance of drugs that are similar to creatinine, which does not show plasma protein binding

False

For a drug that exhibits first order elimination, clearance is proportional to the dose that is given

False

Highly ionized drugs with no affinity to transporters tend to stay in the urine

True

Tubular reabsorption can only be an active process

False

The renal clearance of serum creatinine is identical to GFR

True

The glomerular filtration rate (GFR) is the maximum value of renal clearance

False

Both bound and unbound drug can be filtered

False

Highly ionized substances which have no affinity to tranporters tend to remain in the urine

True

Fluid is filtered across the glomerulus through active transport.

False

The degree of tubular reabsorption might be affected by the pH of the urine.

True

Assume drug A is predominantly cleared through hepatic metabolism. Drug A has an intrinsic clearance of 40,000 L/h. The plasma protein binding and liver blood flow are 60% and 40 L/h, respectively.

How will the increase in liver blood flow to 80 L/h affect AUC when the drug is given orally as a tablet?

↔ AUC

An increase in CL will result in a decrease the Vd

False

For drugs with a hepatic extraction ratio of 0.001, the hepatocyte might represent a distinct diffusion barrier

True

For a drug with a hepatic extraction ratio of 1, enzyme induction will result in an increase in hepatic clearance

False