PK-1

_______________ is measure of the removal of drug from the body a. clearance b. elimination c. residual d. administration

Clearance or drug clearance

Regulatory factors that control gene translation and protein production have no impact on the drug's effect following binding at the receptor. T/F?

FALSE

The density of receptors has no impact on the drug's effect. T/F?

FALSE

When the volume of distribution increases (and clearance remains the same), steady-state plasma concentrations will have more peak-to-trough variation. T/F?

FALSE A larger volume of distribution will result in the same amount of drug distributing in a greater volume, which would result in a lower peak-to-trough variation.

The therapeutic range is the range of plasma drug concentrations that clearly defines optimal drug therapy and where toxic effects cannot occur. T/F?

FALSE Although the therapeutic range of a drug describes a range of plasma drug concentrations generally considered safe and effective in a patient population, no absolute boundaries divide subtherapeutic, therapeutic, and toxic drug concentrations for an individual patient. Both pharmacodynamic and pharmacokinetic factors influence a patient's response.

For a continuous infusion, given the equation C = K0(1 - e-Kt)/Clt ,at steady state the value for t approaches infinity and e-Kt approaches infinity. T/F?

FALSE As t becomes larger, the term e-Kt becomes smaller, and the term 1 - e-Kt approaches 1

Decreasing the dosing interval while keeping the dose constant will result in lower steady-state concentrations. T/F?

FALSE By decreasing the dosing interval the amount of drug administered per unit of time will increase and steady-state concentrations will increase.

Drugs that are very lipid soluble tend to distribute poorly into body tissues. T/F?

FALSE Drugs that are lipophilic can cross membranes and will have good distribution into body tissues.

Drugs that are predominantly unionized at physiologic pH (7.4) have a limited distribution when compared to drugs that are primarily ionized. T/F?

FALSE Drugs that are lipophilic can penetrate membranes and distribute extensively into fat tissue. On the other hand, drugs that are charged at physiological pH will not penetrate into fat tissue and will have a lower distribution.

Highly perfused organs and blood comprise what is usually known as the peripheral compartment. T/F?

FALSE Highly perfused organs and blood comprise what is generally known as the central compartment.

Drugs are generally less well distributed to highly perfused tissues (compared with poorly perfused tissues). T/F?

FALSE Highly perfused tissues generally have higher drug distribution compared to poorly perfused tissues.

Penetration of drug into tissues is not related to the extent bound to plasma proteins. T/F?

FALSE Only free (unbound) drug can penetrate into tissues.

The portion of a drug that is bound to plasma protein is phramacologically active. T/F?

FALSE Only free (unbound) drug is available to interact with receptors and/or enzymes and produce a pharmacological effect.

To determine drug clearance, we must first determine whether a drug bests fits a one- or two-compartment model. T/F?

FALSE Recall that Cl is a model-independent parameter (along with Vd and the elimination rate constant K). Therefore, no assumptions regarding the number of compartments are required.

Since we cannot practically measure drug concentration in specific tissues, we measure it in the plasma and assume that this concentration is the same as that in tissue. T/F?

FALSE The plasma drug concentration is not the same as that in tissue, but rather is related to the tissue concentration by the volume of distribution (Vd). Plasma drug concentrations are commonly used because blood is readily accessible via venipuncture and is the body fluid most often collected for drug measurements.

To calculate drug clearance by the area method, it is necessary to first determine whether the drug best fits a one- or two-compartment model. T/F?

FALSE When using the area method, it does not matter if the drug fits any particular model.

___________________the same drug concentration at receptor site results in reduced effect w/repeated exposure (e.g., opiates, beta-adrenergic receptor agonists).

Pharmacodynamic tolerance

_________________ is the relationship [drug] at site of action & effects.

Pharmacodynamics

_________________ is the time course of what happens to drug in the body.

Pharmacokinetics

Two conditions that may substantially alter volume of distribution are __________________ and _____________.

Severe traumatic & Burn injuries Severely traumatized and burn patients have a cytokine induced, systemic inflammatory response syndrome (SIRS) that results in decreased plasma proteins and an accumulation of fluid in the tissues.

A drug with a relatively small K (long t1/2) takes a longer time to reach steady state than a drug with a large K. T/F?

TRUE

Absorption of a drug from a tablet form involves dissolution of the solid dosage form into GI fluids and diffusion through body fluids and membranes. T/F?

TRUE

Drug pharmacodynamics are affected by the drug concentration at the site of the receptor, density of the receptors on the target cell surface, mechanism by which a signal is transmitted into the cell by second messengers, and regulatory factors that control gene translation and protein production. T/F?

TRUE

For a drug with a narrow therapeutic index, the plasma concentration required for therapeutic effects is near the concentration that produces toxic effects. T/F?

TRUE

Pharmacodynamics includes the time course and intensity of therapeutic and adverse effects. T/F?

TRUE

Plasma refers only to the fluid portion of blood, including soluble proteins but not formed elements. T/F?

TRUE

The concentration of a drug at the receptor determines intensity of drug's effect. T/F?

TRUE

Therapeutic drug concentration monitoring with plasma drug concentration data assumes that pharmacologic response is related to the drug concentration in plasma. T/F?

TRUE

Total body clearance is the sum of clearance by the kidneys, liver, and other routes of elimination. T/F?

TRUE

When multiple drug doses are given and steady state is reached, the amount of drug eliminated during one dosing interval (τ) is equal to the drug dose. T/F?

TRUE

If two formulations of the same drug are tested and product A has a faster absorption rate than product B, product A will take a shorter amount of time to reach peak concentration. T/F?

TRUE Drugs that are absorbed more quickly will also reach a higher peak concentration since less elimination has taken place.

The equation describing elimination after an IV bolus dose of a drug characterized by a two-compartment model requires two exponential terms. T/F?

TRUE One exponent is needed for the distribution phase and the other for the elimination or post-distribution phase.

If you double the infusion rate of a drug, you should expect to see a twofold increase in the drug's steady-state concentration. Assume that clearance remains constant. T/F?

TRUE The changes in the infusion rate will directly affect the plasma concentrations if other factors remain constant. [K0 (new)/Css (desired)] = [K0 (original)/Css (measured)]

A decrease in drug dose will result in lower plasma concentrations at steady state, but will not change the time to reach steady state. T/F?

TRUE The time to reach steady-state is determined by K.

Define "Pharmacokinectics".....

The study of the time course of drug absorption, distribution, metabolism, and excretion.

For a two-compartment model, which of the following is the term for the residual y-intercept for the terminal portion of the natural-log plasma concentration vs. time line? a. A Correct b. beta (β) c. alpha d. B

a. A

For a drug that is totally absorbed without any pre-systemic metabolism and then undergoes hepatic extraction, which of the following is the correct equation for F? a. F = 1 - E b. F = 1 - Ka c. F = 1 - the fraction of the drug absorbed d. F = 1 - Fp

a. F = 1 - E Correct F represents the fraction of drug that reaches the systemic circulation ; E is the extraction ratio.

For the body fluid compartments below, rank them from the lowest volume to the highest, in a typical 70-kg person. a. Plasma < extracellular fluid < intracellular fluid < total body water Correct b. Extracellular fluid < intracellular fluid < plasma < total body water c. Intracellular fluid < extracellular fluid < plasma < total body water d. Total body water < plasma < intracellular fluid < extracellular fluid

a. Plasma < extracellular fluid < intracellular fluid < total body water Water accounts for approximately 60% weight. In a 70 kg person, the approximate volumes are: Plasma = 2.8 L, extracellular fluid = 18 L, intracellular fluid = 25 L, and total body water = 42 L.

Two generic brands of equal strength of a drug (as a tablet) are given orally. Tablet A results in an AUC of 300 (mg/L) × hour, whereas tablet B results in an AUC of 500 (mg/L) × hour. Which product has the better bioavailability? a. Table A b. Tablet B

a. Table B Correct

Which of the following statements regarding "Pharmacodynamics" are true? a. The concentration of a drug at the receptor determines intensity of drug's effect. b. The density of receptors has no impact on the drug's effect. c. Regulatory factors that control gene translation and protein production have no impact on the drug's effect following binding at the receptor. d. Pharmacodynamics includes the time course and intensity of therapeutic and adverse effects.

a. The concentration of a drug at the receptor determines intensity of drug's effect. d. Pharmacodynamics includes the time course and intensity of therapeutic and adverse effects.

The extent to which a drug is absorbed partially determines its: a. bioavailability. b. half-life. c. elimination rate. d. volume of distribution.

a. bioavailability

The body converts a drug to a less active substance by a process called: a. biotransformation. Correct b. distransformation. c. hydrogenation. d. phosphorylation

a. biotransformation.

Factors that cause variability in plasma drug concentrations after the same drug dose is given to different patients include variations in the: a. drug absorption. b. EC50. c. kinetic homogeneity. d. Emax.

a. drug absorption.

Factors that cause variability in plasma drug concentrations after the same drug dose is given to different patients include variations in the: (Select all that apply) a. drug distribution. b. renal insufficiency. c. obesity. d. genetic differences in an individual's ability to metabolize and eliminate the drug.

a. drug distribution. b. renal insufficiency. c. obesity. d. genetic differences in an individual's ability to metabolize and eliminate the drug.

Which of the following pharmacokinetic processes are part of "Drug Disposition"? (Select all that apply) a. excretion Correct b. metabolism Correct c. distribution Correct d. absorption

a. excretion b. metabolism c. distribution

Steady-state plasma concentration is approximately reached when the continuous infusion has been give for at least how many half-lives of the drug? a. five b. ten c. three d. two

a. five At five half-lives, ~97% of the steady-state concentration is reached.

For a drug regimen, if the elimination rate (K) of a drug is reduced while Vd, X0, and τ remain constant, the peak and trough concentrations will: a. increase b. decrease

a. increase

When drug clearance decreases (while volume of distribution remains unchanged), steady-state plasma concentrations will: a. increase b. decrease c. remain the same

a. increase When clearance decreases, plasma concentrations will increase because drug is administered at the same rate (dose and dosing interval) but is being removed at a lower rate.

Drug elimination encompasses both: a. metabolism and excretion. b. metabolism and biotransformation. c. metabolism and distribution. d. absorption and metabolism

a. metabolism and excretion.

Drug distributes to all tissues very rapidly following IV administration of drug: a. one compartment model b. two compartment model c. multicompartment model

a. one compartment model

Instantaneous distribution to most body tissues and fluids is assumed in which of the following models? a. one-compartment b. two-compartment c. multicompartment

a. one-compartment model

EC50 refers to drug concentration at which a. one-half the maximum response is achieved b. tolerance is likely observed. c. the maximal effect is achieved

a. one-half the maximum response is achieved

The study of the time course of drug absorption, distribution, metabolism, and excretion is called: a. pharmacokinetics. b. pharmacodynamics. c. kinetic homogeneity. d. drug concentration

a. pharmacokinetics

If for a drug there is extensive binding to plasma proteins, but not within or to blood cells, would you expect the concentration of a drug in whole blood or plasma to be greater, or are they about the same? The unbound drug concentration is the same in plasma water and cellular fluids. a. plasma b. about the same c. whole blood

a. plasma Plasma contains soluble proteins such as albumin, and has a smaller volume since there are no blood cells present. Therefore, the concentration of drug in plasma > whole blood.

Which of the following are factors that could DECREASE plasma protein concentrations? (Select all that apply) a. renal disease b. trauma, surgery c. liver disease d. Burns

a. renal disease Excessive elimination of proteins can result in decreased plasma protein concentrations b. trauma, surgery Increase protein catabolism resulting in decreased plasma protein concentrations c. liver disease Decrease protein synthesis resulting in decreased plasma protein concentrations d. Burns Distribution of albumin into extravascular space will result in decreased plasma protein concentrations

If for a drug there is no binding to plasma proteins or blood cell components, would you expect the concentration of a drug in whole blood or plasma to be greater, or are they about the same? The unbound drug concentration is the same in plasma water and cellular fluids. a. same b. whole blood c. plasma

a. same Since the drug is not bound to any blood cell components or plasma proteins (e.g., albumin), the concentration whole blood = plasma.

If a drug is poorly distributed to tissues, its apparent volume of distribution is probably: a. small. b. large.

a. small.

Significant first-pass metabolism means that much of the drug's metabolism occurs before its arrival at the: a. systemic circulation. b. portal blood. c. liver lobule. d. hepatocyte

a. systemic circulation.

Examples of situations that would NOT support therapeutic drug concentration monitoring with plasma drug concentrations would be ones in which: (Select all that apply) a. toxic effects may occur at unexpectedly low drug concentrations, as well as high drug concentrations. b. correlation between a drug's plasma concentration and therapeutic concentration is good. c. the toxic plasma concentration is many times the therapeutic concentration range. d. a wide variation in plasma drug concentrations is achieved in different patients given a standard drug dose.

a. toxic effects may occur at unexpectedly low drug concentrations, as well as high drug concentrations. d. a wide variation in plasma drug concentrations is achieved in different patients given a standard drug dose.

The units for clearance are: a. volume/time. b. half-life/dose. c. dose/volume. d. concentration/half-life.

a. volume/time.

Which of the following statements is TRUE regarding EC50 values? a. Drugs with higher EC50 values have a longer duration of action compared to drugs with lower EC50 values. b. EC50 values can be used to compare the potency of drugs in same class. c. EC50 values describe the maximal effect of a drug following binding to a receptor. d. EC50 values can be used to predict whether drug tolerance will develop.

b. EC50 values can be used to compare the potency of drugs in same class.

Which of the following dosage techniques results in the greatest difference between maximum (peak) and minimum (trough) concentrations after a dose? a. None. Both of the other techniques will have the same difference between Cpeak and Ctrough. b. Large doses given at a long dosing interval c. Small doses given at a short dosing interval

b. Large doses given at a long dosing interval

In the two-compartment model, Xp; represents the: a. amount of drug in the body. b. amount of drug in the peripheral component. c. parenteral drug dose. d. fraction of the dose distributing to the peripheral compartment.

b. amount of drug in the peripheral component.

The plasma drug concentration versus time curve for a two-compartment model is represented by what type of curve? a. monoexponential b. biexponential

b. biexponential

For aminoglycoside doses, which of the following must be calculated to estimate an individual patient's drug elimination rate? An individual patient's: a. biliary clearance b. creatinine clearance c. pulmonary clearance + creatinine clearance d. pulmonary clearance

b. creatinine clearance

Biotransformation may be dependent on factors such as age, a. disease, and gender. b. disease, and genetics. c. portal vein and hepatic artery. d. height, and gender

b. disease, and genetics.

If the dose (X0) and AUC are known, the clearance (area method) is calculated by: a. plasma concentration/AUC b. dose/AUC c. AUC/dose d. K/AUC

b. dose/AUC

Pharmacodynamics refers to the relationship of drug: a. dose to drug concentration in plasma. b. drug concentrations to drug effect. c. dose to drug concentration at the receptor site. d. dose to drug effect.

b. drug concentrations to drug effect.

Which of the following statements best describes F? a. speed at which the administered drug reaches the systemic circulation b. fraction of the administered drug that reaches the systemic circulation c. rate of absorption of the administered drug into the systemic circulation d. amount of administered drug that reaches the systemic circulation

b. fraction of the administered drug that reaches the systemic circulation

Which of the following is an example of pharmacokinetic tolerance? a. cellular response to a drug is decreased by desensitization of receptors present by the beta-arrestin protein (e.g., beta-adrenergic receptors) b. increased drug metabolism that results in a decrease in the drug concentration achieved with a given dose of drug Correct c. cellular response to a drug is decreased by down regulation of receptor numbers d. the same drug concentration at receptor site results in reduced effect w/repeated exposure (e.g., opiates)

b. increased drug metabolism that results in a decrease in the drug concentration achieved with a given dose of drug

Which of the following terms describes the predictable relationship between plasma concentration of a drug and the concentration of drug at the receptor where it produces therapeutic effect? a. tolerance b. kinetic homogeneity c. clinical pharmacokinetics d. pharmacodynamics

b. kinetic homogeneity

The basic functional unit of the liver is the: a. renal lobule. b. liver lobule. c. liver cell. d. hepatocyte.

b. liver lobule

Biotransformation is also known as: a. renal excretion. b. metabolism. c. hepatic clearance. d. elimination.

b. metabolism.

For a drug that has first-order elimination and follows a one-compartment model, which of the following plots would result in a straight line? a. plasma concentration vs. time b. natural log of plasma concentration vs. time c. none of the above

b. natural log of plasma concentration vs. time

The liver receives its blood from the: a. portal artery and hepatic artery. b. portal vein and hepatic artery. c. portal artery and hepatic vein. d. vena cava and aorta.

b. portal vein and hepatic artery.

Which of the following dosing techniques results in smaller fluctuations between peak and trough plasma levels? a. large doses relatively less frequently b. small doses very frequently Correct c. Neither. Both options will have the same degree of fluctuations.

b. small doses very frequently

The method of back-extrapolation is used to calculate: a. the area under the plasma concentration vs. time curve b. the rate constant of drug elimination from the body c. the amount of drug present in specific organs

b. the rate constant of drug elimination from the body

Drug distributes to highly perfused tissues very rapidly following IV administration & redistributes to other tissues at slower rate: a. one compartment model b. two compartment model c. multicompartment model

b. two compartment model

Which equation below correctly represents the two-compartment model? a. Ct = A + B*e-Kt b. Ct = A*e-βt + B*e-αt c. Ct = A*e-αt + B*e-βt

c. Ct = A*e-αt + B*e-βt

Which of the following disease states can alter drug distribution? a. liver failure b. renal failure c. all of the above d. heart failure

c. all of the above

Cationic drugs and weak bases are more likely to bind to: a. globulin b. lipoprotein c. alpha-1-acid glycoprotein d. globulin and lipoprotein

c. alpha-1-acid glycoprotein bind basic (cationic) drugs.

The application of pharmacokinetic principles to the safe and effective therapeutic management of drugs in an individual patient is known as: a. pharmacokinetics. b. pharmacodynamics. c. clinical pharmacokinetics. d. kinetic homogeneity.

c. clinical pharmacokinetics

With a drug that follows first-order elimination, the amount of drug eliminated per unit time: a. remains constant while the fraction of drug eliminated decreases. b. remains constant while the fraction of drug eliminated also remains constant. c. decreases while the fraction of drug eliminated remains constant.

c. decreases while the fraction of drug eliminated remains constant. With first-order elimination, the amount of the drug eliminated in any time period is determined by the amount of drug present at the start. Although the amount of drug eliminated in successive time periods may decrease, the fraction of the initial drug that is eliminated remains the same.

With a continuous IV infusion of drug, the steady-state plasma concentration is directly proportional to: a. clearance. b. volume of distribution. c. drug infusion rate The steady-state concentration is directly proportional to the drug infusion rate. d. K.

c. drug infusion rate

Because the extraction ratio can maximally be 1, the maximum value that hepatic clearance can approach is that of: a. renal blood filtration. b. creatinine clearance. c. hepatic blood flow. d. glomerular filtration.

c. hepatic blood flow.

Which of the following is a proper unit for the elimination rate constant? a. minutes b. mg/minute c. hr-1 d. mg/

c. hr-1

For drugs that do NOT distribute into adipose tissue well, Vd is based on: a. adjusted body weight b. total body weight c. ideal body weight

c. ideal body weight Used for drugs that do not distribute into fat tissue.

If for a drug there is extensive binding to blood cell components, but no binding to plasma proteins, would you expect the concentration of a drug in whole blood or plasma to be greater, or are they about the same? The unbound drug concentration is the same in plasma water and cellular fluids. a. plasma b. same c. whole blood

c. whole blood Whole blood contains the blood cell components and therefore the concentration whole blood > plasma.

The amount of drug per unit of volume is defined as the:

concentration

Which of the following parameters are a measure of the organ's ability to remove drug? a. Elimination rate constant (K) b. Clearance (Cl) c. Volume of distribution (Vd) d. Extraction Ratio (E)

d. Extraction Ratio (E)

Which of the following would result in a drug having a HIGH clearance? a. Low extraction ratio + High blood flow b. Low extraction ratio + Low blood flow c. High extraction ratio + Low blood flow d. High extraction ratio + High blood flow

d. High extraction ratio + High blood flow

Anionic drugs and weak acids are more likely to bind to: a. alpha-1-acid glycoprotein b. lipoprotein c. globulin d. albumin

d. albumin binds acidic (anionic) and basic (cationic) drugs

In total, hepatic elimination encompasses both the processes of: a. absorption and demethylation b. oxidation and glucuronidation. c. hydroxylation and oxidation. d. biotransformation and excretion.

d. biotransformation and excretion.

Predict how the volume of distribution (Vd) would change if the unbound fraction of phenytoin in plasma decreased from 90% to 85%. Assume that unbound fraction in tissues (Ft) and volumes of plasma (Vp) and tissues (Vt) are unchanged. a. cannot be predicted with the information provided b. increase c. no change d. decrease

d. decrease

The volume of distribution equals _______ divided by initial drug concentration. a. clearance b. initial drug concentration c. half-life d. dose

d. dose

How is the volume of distribution (Vd) of digoxin likely to change if a patient has been taking both digoxin and quinidine and the quinidine is discontinued? Assume that plasma volume (Vp), tissue volume (Vt), and unbound fraction of drug in plasma (Fp) are unchanged. a. decrease b. no change c. cannot be predicted with the information provided d. increase

d. increase

The liver receives blood supply from the GI tract via the: a. portal artery. b. hepatic vein. c. hepatic artery. d. portal vein

d. portal vein

With a two-compartment model, the term "K12" represents the: a. rate constant for drug transfer from compartment 2 (peripheral) to compartment 1 (central). b. first portion of the natural log of plasma drug concentration versus time curve, where the log concentration rapidly declines. c. elimination rate constant d. rate constant for drug transfer from compartment 1 (central) to compartment 2 (peripheral).

d. rate constant for drug transfer from compartment 1 (central) to compartment 2 (peripheral)

Which of the following is the best definition of beta (β)? a. average elimination rate constant b. initial rate constant of elimination c. terminal half-life d. terminal elimination rate constant

d. terminal elimination rate constant

The most commonly used model in clinical pharmacokinetic situations is the:

one-compartment model