PK models
A one compartment model means?
A.Concentrations are in equilibrium throughout the body; B. There is rapid missing in the blood
C. Elimation processes are all first order
Physiological Model:
A.Faster drug elimination without affecting rate of drug distribution
B.No drug present at time zero and drug level rise gradually to plateau/steady state
C.Highly dependent on drug exposure estimation
D.Presents a more realistic picture of drug disposition in various tissues
To examine the one compartment model, two assumptions are made?
A. Distribution and equilibration is instantaneous; B. Elimination is first order; C. A and B
Instantaneous distribution to most body tissues and fluids is assumed in which of the following models?
A. One-compartment model; B. Two-compartment model; C. Multicompartment model
For a drug that has first-order elimination and follows a one-compartment model, which of the
following plots would result in a curved line?
A. Plasma concentration versus time ;
B. natural log of plasma concentration versus time
Compartmental models are useful for the mathematical description of drug pharmacokinetics
A. True
B. False
Some of the parameters of the two compartment model include k12, k21, k10
A. True
B. False
If a drug is eliminated by first order kinetics then it must follow a one compartment model W6
A. True; B. False
In physiological Model elimination occurs from the central compartment because the major sites of
elimination are highly perfused
A. True;
B. False
---------------------- is driving force in j diffusion model.
A. Active transport- energy requiring; B. Facilitated transport; C. Drug concentration gradient
Clearence
Which of the following statements best defines the total clearance of a drug?
The fraction of drug reaching the systemic circulation after administration;
The fraction of drug removed from the plasma per unit time;
The volume of plasma from which the drug is removed per unit time;
The volume of plasma cleared by the kidney per unit time;
The amount of drug removed from plasma per unit time;
The amount of drug biotransformed by the liver per unit time;
Clearance is
A.Dependent on the value of volume of distribution;
B. Dependent on the value of half-life;
C. A function of the blood flow to clearing organs and the efficiency of the organ in extracting the
drug;
D. A function of the physiologic volume of blood and tissues and how the drug binds in blood and
tissues;
E. A and B.
If a drug that undergoes hepatic clearance is poorly extracted in one pass through the liver, which of
the following is most likely to be true?
A.Clearance is rate-limited by hepatic blood flow;
B.First pass metabolism is significant after oral administration;
C.Oral therapeutic doses are larger than parenteral doses;
D. Protein binding alters drug clearance significantly
Systemic clearance (CLs) is related with:?
A. Only the concentration of substances in plasma;
B. Only the elimination rate constant
C. Volume of distribution, half life and elimination rate constant; D. Bioavailability and half life
Elimination is expressed as follows:
A. Rate of renal tubular reabsorption;
B. Clearance speed of some volume of blood from substance;
C. Time required to decrease the amount of drug in plasma by one-half;
D. Clearance of an organism from a xenobiotic
The units for clearance are:
A. concentration/half-life. B. dose/volume.
C. half-life/dose.
D. volume/time.
Total clearance is defined as the fraction of the volume of distribution (Vd) completely cleared of drug
per unit time by a process of metabolism and/or excretion.
A. True
B. False
All drugs having the same clearance reach the same plateau concentration when given at the same iv
infusion rate.
A. True
B. False
Enzyme induction affects the hepatic clearance of a low and high extraction drugs
A. True;
B. False
The degree of plasma protein binding affects the metabolic clearance of all drugs that are metabolized
in the liver.
A. True;
B. False
For a low extraction drug Hepatic clearance will depend on tissue protein binding
A. True;
B. False
A change in the intrinsic clearance will affect the volume of distribution (Assume a drug which is
eliminated through hepatic metabolism only).
A. True;
B. False
Intrinsic clearance and volume of distribution are independent of each other (Assume a drug which is
eliminated through hepatic metabolism only).
A. True;
B. False
The renal clearance of a drug (as determined by filtration and reabsorbtion) always depends on the
tissue binding of the drug.
A. True;
B. False Protein binding.
For a drug that is mainly eliminated through hepatic metabolism an increase in plasma protein binding
will always result in a decrease of the drug’s hepatic clearance
A. True;
B. False
Clearance determines the maintenance dose required to achieve the desired steady-state concentration
A. True;
B. False
The ratio between the rate of elimination and drug concentration is clearance
A. True;
B. False
Elimination is expressed as clearance of an organism from a xenobiotic
A. True;
B. False
On the hepatic drug clearance affect ----------------------------A. Drug delivery to liver elimination sites;
B. Site of injection;
C. Carrier saturation
Age associated changes in pharmacokinetics include ----------------Reduction in creatinine clearance in 2/3 population;
Decreased body fat;
Increase body water;
A greater reduction in conjugation compared with oxidation
Hepatic clearance of the drugs with Intermediate extraction ratio is dependent on ----------A.Intrinsic metabolizing capacity;
B. Hepatic blood flow;
C. A and B.
Systemic clearance (CLs) is aciciated with -----------------A. Bioavailability and half life;
B. Only the elimination rate constant
C.Volume of distribution, half life and elimination rate constant;
Elimination
Which of the following is most useful in determining the rate of elimination of a drug, in general?
A.Drug concentration in urine (renal elimination); B. Drug concentration in stool (bilary
elimination); C. Drug concentration in blood;
D. Drug concentration in brain ;
E. Drug
oxidation rate.
The ratio between the rate of elimination and drug concentration is
A.Elimination rate;
B. Elimination rate constant;
C. Apparent volume of distribution;
D. Clearance
Metabolism
What phase 1 reaction is mainly performed by the cytochrome P450 enzymes also called mixedfunction enzymes?
A.Hydrolysis;
B. Oxidation;
C. Reduction
Which of the following reactions is phase II and NOT phase I?
A.Oxidations;
B. Reductions; C. Conjugations; D. Deaminations;
E. Hydrolyses
Which of the following processes proceeds in the second phase of biotransformation?
A. Acetylation;
B. Reduction;
C. Oxidation; D. Hydrolysis
Which of the following is NOT a phase II substrate?
A. Glucuronic acid;
B. Sulfuric acid;
C. Acetic acid;
What is an example of a phase II biotransformation?
A. Oxidation;
B. Reduction;
D. Amino acids; E. Alcohol
C. Glycolysis
d. sulfation
Phase II metabolism processes commonly result in metabolites that have a smaller molecular weight
than the parent drug.
A. True;
B. False
When a drug is present in therapeutic amounts, Phase I or II reactions proceed with ___________, and
when a drug is present at toxic concentrations, phase I or II reactions proceed with ________________.
A. Zero-order kinetics; zero-order kinetics; B. First-order kinetics; zero-order kinetics
phase 1- Metabolic transformation is -----------------------Acetylation and methylation of substances;
Transformation of substances due to oxidation, reduction or hydrolysis;
C. Glucuronide formation;
D. Binding to plasma proteins
Elimination rate constant (Kelim) is defined by the following parameter:
A. Rate of absorption;
C. Highest single dose;
B. Maximal concentration of a substance in plasma
D. Half life (t ½)
Half life (t ½) doesn’t depend on:
Biotransformation;
Time of drug absorption;
Concentration of a drug in plasma
D.Rate of drug elimination
For a low extraction drug, changes in plasma protein binding will affect either volume of distribution
or hepatic clearance, as Vd and CL are independent parameters (Assume a drug which is eliminated
through hepatic metabolism only)..
A. True;
B. False
The transport across biological membranes is affected by------------.
drug parameters and physiological parameters;
environmental parameters
Therapeutic drug monitoring (TDM) may be useful especially when TB patients:
A.Are slow to respond to standard treatment;
B. Have minimal disease;
C. Are on isoniazid and rifampin only;
D. Are latently infected with TB;
E. Receiving directly observed therapy (DOT).
The sites for genetic variations that can affect drug response include:
A.Drug metabolizing enzymes;
B. Drug target proteins;
C. Drug transporter proteins;
D. Disease-associated genes;
E. All of the above
Genetic variations in drug targets can contribute to drug ___________
Bioavailability;
Half-life;
Racial differences in response;
Peak-dose area under the curve;
Entry into the central nervous system
The structure of the cell membrane is best described as:
A lipid bi-layer;
B. A rigid, strong layer protecting the cell
C. A n impenetrable barrier;
D. A single lipid layer
Which of the following is a FUNCTION of the cell membrane?
A.Keeps the cell wall in place;
B.Regulates which materials enter and leave the cell
C.Breaks down lipids, carbohydrates, and proteins from foods
D.Stores water, salt, proteins, and carbohydrates
A hydrophilic medicinal agent has the following property:
Low ability to penetrate through the cell membrane lipids;
Penetrate through membranes by means of endocytosis;
Easy permeation through the blood-brain barrier;
High reabsorption in renal tubules
Which of the following do/does NOT enter or exit a cell via the activity of the transport proteins
within the cell membrane?
potassium ions;
oxygen;
glucose
A hydrophilic drugs has low ability to penetrate through the cell membrane lipids
A. True;
B. False
The ability of drugs to cross cell membranes depends on their ________ ___________.
lipid solubility;
enzymes;
water;
systemic circulation
_________ forms ion channels in the cell membrane
cholesterol;
integral membrane proteins;
phospholipids
Most drugs penetrate cell membranes by ------------------Pinocytosis;
Non-ionized passive diffusion;
Filtration through pores;
Ionized active diffusion;
Ionized passive diffusion
For a drug with a narrow therapeutic index, the plasma concentration required for therapeutic
effects is near the concentration that produces toxic effects.
A. True ; B. False
Factors associated with drug absorption that can result in incomplete absorption:
Drug metabolism by gastrointestinal flora;
Drug hydrophilicity (opposite of lipophilicity);
Drug instability in gastric acid;
Presence of food in the GI tract;
E. Drug-drug interactions;
All of them;
Non of them
CYP2D6 polymorphism can affect:
Drug toxicity;
Drug interaction potential;
Drug delivery
D. A and B;
E. B and C
CYP2D6 polymorphism can influence ----------------:
Drug toxicity and Drug interaction potential;
Drug delivery and elimination
The first pass effect refers to:
A. the loss of drug by rapid elimination;
B. the loss of drug by metabolism in the liver
C. the loss of by drug distribution to peripheral tissues
Drug distribution may involve protein binding or transport to various tissues within the body.
A. True
B. False
Which of the following should NEVER be done?
A.Placing tissue intended for banking as a fresh frozen specimen in formalin;
B.Encourage the Operating Room (OR) staff to notify the pathologist or designate about the time of
ischemia (when blood vessels were clamped);
C.Transport the tissue from the Operating Room to the Pathology Lab, using a rapid specimen
D.transport protocol.
Drugs that are extensively distributed into specific tissue regions, such as chloroquine into the liver,
tend to have quite large values for the apparent volume of distribution
A. True
B. False
The tissue uptake of a lipophilic unionized drug is more likely to be perfusion controlled.
A. True;
B. False
For a low extraction drug Hepatic clearance will depend on tissue protein binding
A. True;
B. False
The renal clearance of a drug (as determined by filtration and reabsorbtion) always depends on the
tissue binding of the drug.
A. True;
B. False
Tissue ____________ has a significant role in the initial distribution of a drug.
A. specificity;
B. infusion; C. perfusion
Therapeutic index of a drug ----------------------------A. Is obtained by dividing ED50 by LD50;
B. Is greater if a drug is more toxic
C. Is high if therapeutic widow is narrow;
D. Is low if the drug has more tissue biding
Is low if the slope of its dose-response curve is steep
The only DIFFERENCE between diffusion and facilitated diffusion is
A.Facilitated diffusion requires energy;
B.Facilitated diffusion is the moves substances from an area of low concentration to an area of high
concentration;
C.Facilitated diffusion uses protein channels to move substances in or out of the cell;
D.Diffusion requires energy
If protein plasma binding is decreased, how will volume of distribution be affected?
A.Increased;
B. Decreased;
C. Not changed
In areas of high expression P glycoprotein does what to drug absorption and thus more is transported
out of cells?
A. Reduces;
B. Increases;
C. Don't know;
D. Stays the same
Expression of P glycoprotein is associated with what?
A. Risk of malignancy;
B. Allergies;
C. Multidrug resistance;
D. Anemia
What is the major drug binding protein that can act as a drug reservoir?
A. Plasma albumin;
B. Fibrinogen;
C Globulin
Which of the following processes uses a carrier protein and ATP?
A.Simple diffusion; B. Osmosis; C. Facilitated diffusion; D. Active transport; E. Endocytosis
Acidic drugs are mainly bound in plasma to the protein albumin
A. True
B. False
Basic drugs are mainly bound in plasma to the protein α1 glycoprotein and other globulin proteins
A. True
B. False
For a high extraction drug Hepatic clearance will depend on plasma protein binding
A. True;
B. False
Grapefriut juice is known to inhibit the CYP3A4 metabolism and P-glycoprotein in the small intestine
A. True;
B. False
Slow acetylators is known to inhibit the CYP3A4 metabolism and P-glycoprotein in the small intestine
A. True;
B. False
If a particular protein was identified in the plasma membrane to cause organ transplant rejection, such
a protein would be considered a(an) ______ protein.
A. Carrier;
B. channel;
C. cell-recognition
Sodium and potassium ions are transported across the plasma membrane by a ______ protein.
A. Carrier;
B. channel;
C. cell-recognition
Plasma protein binding of drugs ------------------------A. Prolongs the half life of drugs;
B. Increases the bio-availability of drugs
C. Increases the renal clearance of drugs; D.Increases the volume of distribution of drugs
Functional groups within a drug are typically additive to resulting biological actions
A. True
B. False
Typical properties of carrier-mediated drug transport:
A. Non-saturable;
D. B and C;
B. Active transport;
E. None of them
C. Energy requiring;
The sites for genetic variations that can affect drug response include:
A.Drug metabolizing enzymes;
D. Disease-associated genes;
B. Drug target proteins; C. Drug transporter proteins;
E. All of the above
Factors associated with drug absorption that can result in incomplete absorption:
A. Drug metabolism by gastrointestinal flora; B. Drug hydrophilicity (opposite of lipophilicity);
C. Drug instability in gastric acid;
D. Presence of food in the GI tract;
E. Drug-drug interactions;
F. All of them;
G. Non of them
The longer is the gastric emptying time, than lesser is the gastric emptying rate:
A. True
B. False
Warm foods and drinks help increase gastric emptying which accelerates absorption.
A. True
B. False
the gastric emptying time of an older adult and a premature infant are slow and result in increased drug
absorption
A. True
B. False
Organic acids are well absorbed since they are almost completely ----------------at gastric pH.
A. non-ionized;
B. ionized
What is the function of the villi in the small intestine?
A.To decrease the amount of exposed surface;
B. To increase the surface area for absorption & secretion;
C. To facilitate enzyme retention and dispersal;
D. To sweep particles across the surface with wavelike actions
A drug that is a weak organic acid (pK=3) would be least ionized in the:
A.Large intestine (pH=8);
B. Pulmonary alveoli (pH=7.4); C. Small intestine (pH=6);
D. Stomach (pH=2)
If two formulations of the same drug are tested and product A has a greater absorption rate than
product B, product A will take a longer time to reach peak concentrations (Tmax)
A. True;
B. False It would for a low extraction drug
Which of the following are parenteral methods of administration (the others being enteral)? W1
A.Oral;
B. Subcutaneous;
C. Sublingual;
D. Buccal;
E. Rectal
Which of the following is most useful in determining the rate of elimination of a drug, in general?
A.Drug concentration in urine (renal elimination); B. Drug concentration in stool (bilary
elimination); C. Drug concentration in blood;
D. Drug concentration in brain ;
E. Drug
oxidation rate.
Given a graph of plasma drug concentration versus time, what part of the graph would be used to
calculate bioavailability for a PO (oral) drug administration
A. Maximum concentration;
B. Steady concentration;
C. Derivative of the curve (slope)
D. Integral of the curve (area underneath);
E. The curve is not used to calculate
bioavailability
The EC50 refers to the drug concentration at which:
A. One-half the maximum response is achieved;
C.Tolerance is likely to be observed
B. The maximal effect is achieved;
Which of the following groups of people is the least likely to have biotransformation effects due to
altered hepatic function?
A. Infants;
B. Adults;
C. Elderly;
D. Chronic alcoholics
Where is a drug concentration greater?
On the side of the membrane where the drug is more ionized
On the side of the membrane where the drug is less ionized??????
How is the volume of distribution of a drug calculated?
Total dose of the drug divided by the plasma concentration at time=0
Theoretical volume of plasma that is completely cleared of a drug at a given time
Time it takes the drug concentration to fall 1/2
The time it takes for the total amount of drug to decrease by 1/2
Therapeutic drug concentration monitoring with plasma drug concentration data assumes that
pharmacologic response is related to the drug concentration in plasma.
A. True ; B. False
Higher Vd relates to --------------------------A. Longer elimination;
B. Shorter elimination;
C. No change in elimination time