Pharmacokinetics Flashcards
The protein-binding of a drug
A. Will render the drug inactive
B. Will enable the drug to cross membranes
C. Enables the drug to undergo metabolism and excretion
D. Is subject to competition and would be clinically important across any degree of protein-binding
E. AOTA
A
For at least 99% of the drug to be removed from the body after a single dosing under the first-order kinetic reaction, this minimum number of half-lives should have been completed
A. 3 B. 5 C. 7 D. 9 E. 12
C
Pharmacokinetic parameters in distribution is/are:
A. Bioavailability and half-life B. Protein binding and apparent volume of distribution C. Half-life and clearance D. A and B E. B and C
B
Oral bioavailability is dependent on liver and renal metabolism. T/F
F
Bioavailability is a measure of drug absorption, may be affected by first pass metabolism but not by renal metabolism/clearance
Noncompartmental analysis is appropriate only for 1-compartment model. T/F
F
Non-compartmental analysis holds no assumptions in the compartmentalization of drug distribution
The intravenous route is considered 100% absorption. T/F
T
Since all of the drug administered enters the systemic circulation
Oral and IV AUC are adequate to compute for oral bioavailability provided that the doses are the same. T/F
T
The most important of the CYP450 enzymes is CYP3A4 because it metabolizes 33% of all drugs that are metabolized. T/F
F
It metabolizes over 50% of the prescription drugs metabolized by the liver.
For a drug that behaves in a linear fashion, doubling the dose would mean doubling the Cmax and AUC. T/F
T
In first order reactions, rates are linearly related to dose administered.
If the Ka is increased, absorption is faster and Cmax will be attained earlier. T/F
T
An increase in Ka (rate of absorption), will lead to a lower Tmax—hence faster absorption and Cmax reached earlier
In a one-compartment model with first order input and first order elimination, absorption stops when Cmax is reached. T/F
F
Once Cmax is reached, absorption does not stop, it’s just that Ke>Ka rate of elimination is faster than absorption, hence the graph starts to go down
For a first-order, two compartment equation, distribution is immediate and instantaneous within the same compartment. T/F
F
In a 2-compartment model, the distribution phase from the central to the peripheral compartment is signified by the steeper initial slope of the graph, hence it’s not immediate.
If there is a change in plasma protein binding, the impact will be greater in a drug that is more highly protein-bound than one which is less protein-bound. T/F
T
Scenario where there is 1% decrease in protein binding: 99% protein bound- from 1% free drug becomes 2% which is a 100% increase 90% protein bound- from 10% free drug becomes 11% which is a 10% increase
Absolute bioavailability always varies from 0 to 1. T/F
T
It’s a ratio between BA in oral and IV administration.
Vd should always match actual body fluid compartments. T/F
F
Volume of distribution is a hypothetical volume, hence it can be larger than actual body fluid volumes.
The therapeutic margin ranges from the minimum therapeutic concentration to the maximum therapeutic concentration. T/F
F
Aka therapeutic index: ratio of the minimum toxic dose, and the minimum effective dose
Increasing dosage will always increase therapeutic effect. T/F
F
When ceiling dose is reached, increased dose will not result to increased response (hyperbolic graded dose-response curve)
Regardless of the number of compartments, when the equilibrium is reached, the whole system behaves like a one compartment model. T/F
T
When the drug distribution to all compartments reaches equilibrium, it acts like a one compartment model
The purpose of metabolism is to convert the drug into a more polar form and make them more excretable by the kidneys. T/F
T
A drug that is highly protein-bound would have a high volume of distribution. T/F
T
A highly protein bound drug stays intravascularly, hence Vd will be limited to the intravascular blood volume.
After giving a drug repeatedly for 8 half-lives, we are confident that it is in steady state concentration
T
Steady state is achieved after 4-7 half lives
The half-life of a drug is 8 hours. What is the plasma drug concentration after 24 hours if the current concentration is 100 pmol/L?
A. 25 pmol/L B. 16.33 pmol/L C. 12.5 pmol/L D. 6.25 pmol/L E. 3.125 pmol/L
C
In 24 hours= 3 half lives.
After 1st 8 hours= 50 pmol/L
After 2nd 8 hours= 25 pmol/L
After 3rd 8 hours= 12.5 pmol/L
If clearance is reduced by 50% and volume of distribution is doubled, half-life is equivalent to
A. Reduced by 75%
B. Increased by 1.33x
C. Increased by 4x
D. No change
C
t ½ = 0.693Vd/ Cl
t ½ = 0.693 (2) Vd/ 0.5Cl
t ½ = 4(0.693Vd/ Cl)
What happens to bioavailability as the dose increases when there is saturable liver metabolism?
A. Increase
B. Decrease
C. Remains the same
A
When first pass metabolism has been saturated, the additional dose will not undergo first-pass anymore, hence BA increases
What happens to clearance as the dose increases when there is saturable liver metabolism?
A. Increase
B. Decrease
C. Remains the same
B
Clearance is the quantification of elimination (metabolism + excretion), so with a saturable metabolism, clearance will decrease in increased dosing
What happens to bioavailability as the dose increases when there is saturable renal absorption?
A. Increase
B. Decrease
C. Remains the same
C
BA is not affected by renal absorption
What happens to bioavailability as the dose increases when there is saturable dissolution?
A. Increase
B. Decrease
C. Remains the same
B
Drug dissolution is necessary for drug absorption so a saturable dissolution rate will decrease the bioavailability of the drug
2.4 g in 1 day required, maximum of 17 hours dosing interval. What dosing will you use?
A. 800 mg in 8 hours B. 1.2 g in 12 hours C. 1.6 g in 16 hours D. AOTA E. A and B only
E
With C, after 24 hours, the patient is only received 1.6g
Formula for half-life in first order kinetics
A. Vd/CL
B. (VD x ln 2)/CL
C. (CL x ln 2)/ VD
D. ln 2 / (0.693 x k)
B
Pharmacokinetics is:
A. Deals with what body does to the drug
B. Consists of disposition and elimination
C. Consists of absorption, distribution, metabolism and excretion
D. A and C
D
Proactive drugs are used for the ff.:
A. For easier oral absorption
B. Improve safety
C. To test the liver
D. A and B
E. AOTA
D
The Cyp450 microsomal enzyme that is responsible for most (greater part of) metabolism of drugs:
A. Cyp1A (Another one said Cyp2A1)
B. Cyp3A4
C. Cyp2C1
D. Cyp2D1
E. Cyp2E1
B
For 99% of the drug to be eliminated from the body, the minimum number of half-lives that should have been completed is:
A. 3
B. 4
C. 5
D. 6
E. 7
E
Absorption of IV is 100%. T/F
T
Among the CYP450 enzymes, CYP3A4 is the most important because it metabolizes 33% of all drugs. T/F
T
Agonist binding has both efficacy and affinity. T/F
T
For a drug that behaves in a linear fashion, doubling the dose would mean doubling the Cmax but not AUC. T/F
F
An increase in Ki would mean an increase CL (faster) therefore Cmax is reached earlier. T/F
T
Clearance of a drug is:
A. Volume of the drug cleared per unit of
B. Dependent on the blood flow to the clearing organ
C. Equal to the elimination constant
D. AOTA
E. A & B only
*
Given a drug in the body with initial concentration of 100 mg/L and half-life of 12 hours, what is the concentration of the drug 24 hours later?
A. 50 mg/L
B. 25 mg/L
C. 15 mg/L
D. 5 mg/L
A
What happens to the half-life of a drug if clearance is decreased by 75%?
A. T1/2 will be 4x as long B. T1/2 will be 32X as long C. T1/2 will be decreased by 75% D. There will be no effect.
*
What is the best parameter in assessment of bioavailability in a particular route?
A. Half-life
B. Cmax
C. Tmax
D. AUC
E. Clearance rate
*
Clinical pharmacokinetic testing is done to:
A. (Determine) Drug response to the body
B. Establish dosing regiment
C. Determine if drug regimen is appropriate to patients.
D. AOTA
E. B and C
E
With continued infusion, steady state is achieved:
A. Dosing rate = rate of elimination
B. Length of dosing is twice the biological half-life
C. Total amount = required loading dose
D. AOTA
e. A & C only
A
Analysis of compartment models
A. Applicable to extravascular routes
B. Direct relationship between concentration and effect
C. Used with drugs with narrow therapeutic window
D. AOTA
D
Biologic half-life of theophylline in this patient is?
A. 2 hours
B. 3 hours
C. 4 hours
D. 5 hours
*
Parenchymal liver disease affects what most?
A. Absorption
B. Distribution
C. Excretion
D. Metabolism
D
An anti-infective drug excreted 75% or unchanged in the kidney:
A. Methotrexate
B. Atenolol
C. Imipanem
D. Methicillin
D
Therapeutically equivalent drugs should have the ff. characteristics except:
A. Safe and effective B. Pharmaceutically equivalent and bioequivalent C. Same configuration, packaging, preservatives and expiration date D. Adequately labeled and manufactured in compliance with current GMP E. NOTA
E
Cmax 88.7 98.7
AUC 0 - t 89.1 95.1
AUCt-∞ 98.1 121.1
Which of the following is true?
A. Pharmaceutical equivalent, bioequivalent B. Pharmaceutical equivalent, not bioequivalent C. Pharmaceutical alternative, bioequivalent D. Pharmaceutical alternative, not bioequivalent E. Pharmaceutical equivalent, therapeutic equivalent
*
Using the relationship between volume of distribution, clearance, elimination rate constant, and half life, find out what happens to the half life of a drug if clearance is decreased by 50%
A. Half life will be increased by 50%
B. Half life will be increased by 100%
C. Half life will be decreased by 50%
D. Half life will be decreased by 100%
B
Using the relationship between volume of distribution, clearance, elimination rate constant, and half life, find out what happens to the half life of a drug if the volume of
distribution increase by 50% and clearance are simultaneously decreased by 50%
A. Half life will be increased by 50%
B. Half life will be decreased by 50%
C. No change
C
Using the relationship between volume of distribution, clearance, elimination rate constant, and half life, find out what happens to the half life of a drug if the volume of
distribution and clearance are simultaneously decreased by 50% no change
A. Half life will be increased by 50%
B. Half life will be decreased by 50%
C. No change
C
In the first order compartment model, half life is equivalent to:
A. ln2/Vd
B. (ln2)(Vd)/CL
C. ln2(CL)/Vd
B
You want to give your patient 2.4 g of drug X per day. If the computed maximum dosing interval is 12.5 hours, which of the following is/are appropriate dosing regimens?
A. 1.2 grams every 12 hrs B. 800 grams every 8 hours C. 600 grams every 4 hours D. A & B E. All of the above
D
CYP 450 enzymes are called phase 2 metabolic enzymes. T/F
F
CYP 450 enzymes are called phase 1 metabolic enzymes. Since they are oxidoreductases, Redox reactions are under phase I reactions
True or False: If drug X is metabolized into an inactive metabolite, and its inactive metabolite is excreted by the kidney, its mode of elimination is by metabolism and excretion.
F
True or False: In a one compartment model that followed first order input and first order elimination, elimination starts after mass excretion
F
True or False: If clearance of drug X is decreased by half, one needs to decrease its loading dose by 50%
F
Receptors can create new function by binding. T/F
F
The apparent volume of distribution is:
A. Physiological
B. Relatively low for weakly acidic drugs
C. Relatively high for weakly basic drugs
D. Can range from 8-500L or even 35,000
E. All except A
E
Of all the hepatic cyclic proteins forming binds the more that it is responsible for the greatest number of drugs is:
A. CYP 3A
B. CYP 450
C. CYP 27A1
D. CYP 1B1
A
The following parameter is used to assess and measure the extent of absorption of a drug by a particular route
A. Elimination B. AUC C. Cmax D. Tmax E. Half life
B
Bakit kailangan pag-aralan ang pharmacokinetics?
A. Upang malaman ang angkop na dosage, optimum drug concentration
B. Upang mabigay sa pasyente ang pinakmataas na antas ng serbisyong pangkalusugan
C. Lahat ng nasa itaas
C
Drug elimination is said to be first order if
A. The log plasma concentration - time curve is linear
B. The amount of drug eliminated per unit time is constant
C. the amount eliminated per unit time varies with the amount remaining
D. A and C only/AOTA
D
With repeated dosing or continued inclusion of a drug, the steady state is achieved when:
A. The dosing rate is equal to the rate of elimination
B. When the time elapsed after the 1st dose have reached 5 times its half life
C. Both
D. Neither
C
The apparent volume of distribution of a drug is defined as:
A. The volume to which a drug appears to distribute itself with the concentration equal to that of plasma after equilibration has been attained
B. Equivalent to the plasma volume when all of a drug is bound to plasma proteins
C. Both
D. Neither
C
Compartmental model analysis is appropriate when:
A. Analyzing drugs administered through the parenteral route
B. Assuming that there is a direct relationship between the drug concentration and the absolute elimination rate
C. Analyzing drugs that operate on a narrow therapeutic range
D. All of the above
B
True of the two compartment pharmacokinetic model:
A. The rapid initial decline of drug concentration in the plasma is mainly due to distribution and not elimination
B. Drug elimination occurs even before distribution to the compartment is completed
C. The initial secretion phase is important to consider for drugs
D. All of the above
D
When the semilogarithmic plasma concentration time is linear from time 0 to infinity after a single IV administration of a drug, the following are true:
A. One compartmental model is appropriate for this drug
B. Two compartmental model drug can’t be used
C. Biological half-life can be graphically determined
D. All of the above
E. A & C only
E
True of digoxin
A. Bioavailability is 75%
B. Half life is 40 hours
C. 2/3 is unchanged excreted in kidney
D. Inhibits NA-K ATPase pump
D
Factor/s that enhance/s absorption
A. Micronization of drug particles B. Mechanisms that lead to non-ionized moiety C. Organ/tissue perfusion D. A and B E. B and C
D
Factors that enhance absorption are
A. Micronization (reducing the size of the particles in a solid drug product)
B. Mechanisms that lead to the non-ionized moiety (which is the lipoidal form of the drug)
C. Cardiac output
D. A and B
E. B and C
D
Factors that delay gastric emptying:
A. fasting B. vigorous exercise C. Billroth surgery D. lying on the right side E. cold meals
B
Among the hepatic cytochrome P450 enzymes, the one responsible for metabolizing the most number of drugs is:
A. CYP3A B. CYP2C C. CYP2D D. CYP1A E. CYP2E
A
Metformin has a half life of 6 hours. If Raymond’s plasma concentration level is 1mcg/L at noon, after how many hours will is plasma concentration level be 0.25mcg/L?
A. 6 hours
B. 12 hours
C. 18 hours
D. 24 hours
B
Which of the following assumes drug distribution is instantaneous and even?
A. Non compartmental anaylsis
B. 1 compartmental model
C. 2 compartmental model
D. Physiological analysis
B
Volume of distribution is:
A. Plasma volume
B. Extracellular fluid
C. Intracellular fluid
D. Total body water
E. None of the above
E
Clearance is decreased by 50%
A. T1/2 will decrease by 1/2
B. T1/2 will be twice longer
C. T1/2 will be decreased by 1/4
D. No effect on T1/2
B
Volume of distribution is decreased by 50%
A. T1/2 will decrease by 1/2
B. T1/2 will be twice longer
C. T1/2 will be decreased by 1/4
D. No effect on T1/2
A
The equation for half-life for a first order
A. ln 2 / CL B. ln 2 / Vd C. CL / Vd D. ln 2/ K E. ln 2 / (0.693 * K)
D
Given: 2.4 g for 24 hours with maximum dosing interval of 7.5 hours
A. 800 mg every 8 hours
B. 600 mg every 6 hours
C. 600 mg every 4 hours
B
Among the cytochrome P450 enzymes, CYP (unreadable) is the most important because it metabolizes 80% of all drugs that are metabolized. T/F
F
Elimination and excretion are interchangeable terms. T/F
F
If Drug X is metabolized to an inactve metabolite, then excreted via the kidney, the mode of elimination is excretion. T/F
F
In non-compartmental analysis, Cmax and Tmax are obtained from a complex equation. T/F
F
Oral bioavailability solely depends on hepatic metabolism. T/F
F
Noncompartmental analysis reduces the assumptions that must be made in modeling concentration versus time data: An advantage of noncompartmental analysis is that it requires fewer assumptions than that which is necessary with compartmental analysis. It also avoids some of the common problems seen with compartmental analysis.
In a first-order, two-compartment equation, drug distribution is immediate and instantaneous within the compartment. T/F
T
In therapeutic drug monitoring, it is standard to obtain plasma sample as at the estimated time peak. T/F
F
Drug elimination is classified as first order if
A. the amount of drug eliminated is a constant fraction of the remaining drug
B. the amount of drug eliminated is constant
C. the log concentration-time curve is linear
D. all of the above
E. a and b only
F. a and c only
F
The apparent volume of distribution of the drug
A. Is the volume that appears to contain the drug equal to the plasma concentration after equilibriation has been attained
B. Equal to the plasma volume if all the drug is bound to plasma proteins
C. Equal to the total body water volume if the drug is not accumulated in tissues
D. All of the above
E. A and B
F. A and C
E
One compartment model
A. Follows first order rate B. Distributes to single compartment C. Applies zero order kinetic input rate D. All of the above E. A and B F. A and C
F
Most relevant
A. Cmax
B. Tmax
C. AUC total
A
True of pharmacokinetic drug interactions:
A. Affect the site of action
B. Affect the activity of metabolic enzyme systems
C. IV incompatibility
D. AOTA
B
Factors affecting absorption of a drug
A. CO
B. Relative permeability of tissues to drug
C. Degree of ionizability of a drug and lipid solubility
D. AOTA
E. NOTA
C
The oral route of administration
A. Can have aberrant absorption B. Requires the patient to be awake, oriented, and compliant C. Is safe, convenient and economical D. AOTA E. Only B and C
D
Metabolism or Biotransformation
A. Involves the first-pass effect
B. is part of the mechanism that leads to elimination
C. In special circumstances, converts an inactive pro-drug to its active form
D. Converts an active drug to metabolites through a series of chemical reactions
E. AOTA
E
Of all microsomal enzymes, the most common cytochrome P450 metabolizing enzyme is:
A. CYP 3A B. CYP 2D C. CYP 1A D. CYP 2C E. CYP 2B
A
A drug that is completely retained in the plasma compartment would have a volume of distribution equal to which of the following (assume a 70 kg person and that plasma volume is 4% of body weight)?
A. 1.4L
B. 2.8L
C. 5.6L
D. 8.4L
*
Which of the following characterizes clearance capacity-limited elimination?
a. constant fraction of remaining drug is eliminated per unit time
b. has a constant half-life
c. clearance varies depending on concentration of the drug
d. rate of elimination is faster when drug concentration is higher
C
Which of the following routes of administration is greatly affected by the first pass effect?
a. Intramuscular
b. Intravascular
c. Rectal
d. Inhalation
D
Drug A and B are eliminated from the body by metabolism in the liver. Drug A has a clearance of 1.5L/min which is approximately equal to liver blood loss whereas Drug B has a clearance of 0.1 L/min. When these drugs are administered with another drug that increases hepatic drug metabolizing enzymes, which of the following is most likely?
a. Clearance of Drugs A and B will increase
b. clearance of Drugs A and B will decrease
c. Only the clearance of Drug B will Increase
d. Only the clearance of Drug A will increase
C
Which of the following apply to the concept of drug accumulation
a. occurs if dosing interval is shorter that the drug’s half life
b. directly proportional to the fraction of drug lost
c. dosing interval longer than six half-lives.
A
Which of the following is true of loading dose?
a. directly related to clearance
b. requires monitoring to prevent toxic levels
c. decrease time needed to attain steady state concentration
d. AOTA
D
Primary determinant of Css
A. Volume of distribution
B. tmax
C. clearance
D. half life
C
You have a patient in the ER presenting with tonic-clonic seizures. Immediate action is needed. What is the best route of administration of diazepam?
A. Intravenous
B. Intramuscular
C. Subcutaneous
D. Rectal
A
A drug, almost cleared by glomerular filtration, is given at 100 mg, 3x a day. Creatinine clearance is found out to be1/3 that of normal. What would be the initial dosage?
A. 20 mg, 3x a day
B. 33 mg, 3x a day
C. 100 mg, once a day
D. B and C
D
The statement regarding kinetic process is/are true:
a. Ion trapping is a mechanism wherein weak acids become ionized in the presence of urinary acidic pH
b. In overdose state, protein binding sites become saturated which results in an increased fraction of unbound drug
c. Bioavailability is a process wherein drugs/substances become inactivated
d. A and B only
e. AOTA
B
Important pharmacokinetics parameters in therapeutic drug monitoring:
a. Half-life
b. Peak concentration
c. Trough concentration
d. A and B only
e. All of the above
E
What are the goals of pharmacokinetic analysis?
A. Determine the effect of the drug B. Establish/adjust dosage regimen C. Rational drug use D. Prognosis of poisoning E. All of the above.
E
Drug elimination is said to be first order if:
a. The amount of the drug eliminated is a constant fraction of the concentration of the remaining drug.
b. The fraction of the drug eliminated is constant with respect to the amount of the drug eliminated.
c. The log concentration-time curve is linear at the elimination phase.
d. The absolute amount of the drug elimination is independent of the drug concentration.
A/B
One compartmental model:
a) assume 1st order transfer process
b) assume only one compartment in the body in which drug distribute itself
c) can be applied to zero-order input
d) not applicable to drugs administered subcutaneously
e) not applicable to drugs with enterohepatic circulation
A/B/E
Two compartmental model:
a) the initial rapid decline is due to distribution phase and not elimination phase
b) elimination does not occur until Cmax is attained
c) initial distribution is important for drugs that have narrow margin of safety
d) plasma concentration steady state cannot reflect steady state at the site of action
e) T½ cannot be estimated by plasma concentration – time curve
A/C
