Fick's First Law Quiz and Flashcards: Diffusion and Diffusivity

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Questions and Answers

According to Fick's first law of diffusion, which factor does NOT affect the diffusivity (D) of a drug molecule?

Molecular size of the drug

Concentration gradient of the drug (correct)

Surface area of the membrane

Lipophilicity/ionization of the drug

How does the ionization of a drug molecule affect its ability to pass through a lipid bilayer membrane?

Charged (ionized) molecules are trapped on one side of the membrane, while uncharged molecules can freely diffuse

Charged (ionized) molecules diffuse more readily through the lipid bilayer

Uncharged (neutral) molecules diffuse more readily through the lipid bilayer (correct)

Ionization does not affect the diffusion of drug molecules through the lipid bilayer

Which of the following is the LEAST likely to be affected by the ionization of a drug molecule?

Liberation

Distribution

Absorption

Elimination (correct)

A drug with a pKa of 4.4 is a weak acid. If the drug is in plasma (pH 7.4) and gastric juice (pH 1.4), how will the ionization of the drug differ between the two environments?

The drug will be more ionized in the plasma (pH 7.4) compared to the gastric juice (pH 1.4) Signup and view all the answers

Which of the following is the LEAST likely to be affected by increased blood flow to the site of administration?

Elimination of a drug Signup and view all the answers

Which of the following is an example of facilitated diffusion, as opposed to passive diffusion?

The transport of glucose across the intestinal epithelium Signup and view all the answers

Which of the following statements about active transport proteins is correct?

They can facilitate both uptake into the cell and efflux out of the cell. Signup and view all the answers

What can happen when two xenobiotics compete for the same active transport protein?

They can inhibit each other's transport in a noncompetitive manner. Signup and view all the answers

What is the consequence of the induction of active transport proteins?

Increased genetic expression and increased protein synthesis. Signup and view all the answers

Which of the following statements about the blood-brain barrier is correct?

Smaller lipophilic molecules can easily enter the brain across the cellular membrane. Signup and view all the answers

Which of the following membranes are relatively non-porous, allowing only lipophilic or non-ionized molecules to passively diffuse across?

Renal tubular membranes Signup and view all the answers

Which of the following statements about the hepatic blood vessels is correct?

The capillaries are lined with a basement membrane broken by slit junctions (fenestrations). Signup and view all the answers

In an acidic environment (pH < pKa), an acidic drug will be:

Mostly unionized and free to leave Signup and view all the answers

For a basic drug in an alkaline environment (pH > pKa), which form is more predominant?

Unionized form Signup and view all the answers

Which transport mechanism is NOT affected by the ionization state of a drug?

Both b and c Signup and view all the answers

In a neutral environment (pH = pKa), what is the ratio of ionized to unionized forms for an acidic drug?

Ionized = Unionized Signup and view all the answers

Which statement is TRUE about the absorption of ionized drugs?

Ionized drugs generally have lower absorption than unionized drugs Signup and view all the answers

In the elimination process, which form of a basic drug is more likely to be excreted?

Unionized form Signup and view all the answers

Will the transcription and translation of proteins needed for the induction of transporters occur rapidly with the first dose or over time with repeated dosing?

Over time with repeated dosing Signup and view all the answers

What is the most likely route of administration based on the information provided?

IV Signup and view all the answers

What is the half-life (t1/2) for elimination of the drug based on the given data?

5 hours Signup and view all the answers

What is the apparent volume of distribution (Vd) of the drug according to the calculations provided?

12.5 L Signup and view all the answers

What is the clearance of the drug based on the information given?

1.75 L/hr Signup and view all the answers

Which of the following suffixes often indicates a sustained-release drug formulation?

-SR Signup and view all the answers

Which of the following routes of administration is most likely to result in first-pass metabolism of a drug?

Oral (PO) Signup and view all the answers

Which of the following is a potential advantage of the subcutaneous (SC) route of drug administration?

Avoidance of first-pass metabolism Signup and view all the answers

Which of the following describes a drug that exhibits zero-order elimination kinetics?

The rate of elimination is constant over time Signup and view all the answers

Which of the following is a characteristic of Michaelis-Menten enzyme kinetics?

The rate of enzyme-catalyzed reactions becomes saturated at high substrate concentrations Signup and view all the answers

What is the consequence of two xenobiotics competing for the same active transport protein?

Decreased absorption of both xenobiotics by the cell Signup and view all the answers

What is the main effect of active efflux mechanisms at the blood-brain barrier?

Limiting the entry of polar compounds into the brain Signup and view all the answers

How do smaller lipophilic molecules typically enter the brain?

By passing through cellular membranes Signup and view all the answers

In which scenario can only lipophilic or non-ionized drugs be passively reabsorbed in renal tubules?

In acidic environments Signup and view all the answers

How does induction of transport expression affect protein synthesis?

Leads to increased genetic expression and protein synthesis Signup and view all the answers

Which route of drug administration has 100% bioavailability?

Intravenous Signup and view all the answers

According to Fick's first law of diffusion, which factor DOES affect the diffusivity (D) of a drug molecule?

Molecular weight Signup and view all the answers

In an acidic environment (pH < pKa), an acidic drug will be predominantly in which form?

Unionized Signup and view all the answers

Which transport mechanism is affected by the ionization state of a drug?

All of the above Signup and view all the answers

Which of the following is an example of zero-order elimination kinetics?

Metabolism of a drug by a saturable enzyme system Signup and view all the answers

Which kinetic process is characterized by a constant fraction of the remaining drug being eliminated per unit time?

First-order elimination Signup and view all the answers

What is the primary advantage of controlled-release drug formulations over immediate-release formulations?

Maintenance of more consistent drug levels Signup and view all the answers

Which of the following statements about zero-order elimination kinetics is true?

The rate of elimination is constant, regardless of drug concentration Signup and view all the answers

Which of the following factors can influence the rate of hepatic drug metabolism?

All of the above Signup and view all the answers

What is the primary factor determining the extent of passive diffusion across a membrane for an ionized drug?

Degree of ionization Signup and view all the answers

Which of the following statements about first-order elimination is correct?

The rate of elimination is directly proportional to the drug concentration in the body. Signup and view all the answers

Which of the following best describes the Michaelis-Menten equation in enzyme kinetics?

It describes the relationship between substrate concentration and enzyme activity at non-saturating substrate concentrations. Signup and view all the answers

In the context of drug delivery, what is the purpose of sustained-release formulations?

To maintain a constant drug concentration in the body over an extended period. Signup and view all the answers

Which of the following statements about zero-order elimination is correct?

The rate of elimination is independent of the drug concentration in the body. Signup and view all the answers

Which of the following is a common phase I reaction in drug metabolism?

Oxidation Signup and view all the answers

According to the information provided, if a patient drinks a large quantity of grapefruit juice (a p-glycoprotein inhibitor), the blood levels of propranolol will:

Increase, as p-glycoprotein will be inhibited from transporting propranolol out of the cell Signup and view all the answers

For the induction of transporters to occur, the increased transcription and translation of the necessary proteins will happen:

Over time, with repeated dosing of the inducing agent Signup and view all the answers

For a weak acid drug with a pKa of 3.5, such as aspirin, the drug will be most greatly absorbed via diffusion in the:

Stomach (pH ~2), where the drug is predominantly unionized Signup and view all the answers

For a basic drug with a pKa of 7.3, which urine pH would result in a higher amount of the drug being excreted?

pH 8, as the drug would be predominantly unionized Signup and view all the answers

If two xenobiotics compete for the same active transport protein, what is the likely outcome?

The transport of one xenobiotic will be increased, while the other will be decreased Signup and view all the answers

Which of the following statements about first-order elimination is correct?

The rate of elimination is directly proportional to drug concentration Signup and view all the answers

In enzyme kinetics, the Michaelis-Menten constant (Km) represents:

The substrate concentration at which the reaction rate is half of Vmax Signup and view all the answers

In the context of drug delivery, what is the primary advantage of zero-order elimination kinetics?

It allows for a more controlled and sustained release of the drug Signup and view all the answers

Which of the following statements about drug metabolism is correct?

Phase II metabolism involves the conjugation of the parent drug or its metabolite Signup and view all the answers

Which of the following factors does NOT affect the rate of passive diffusion across a membrane?

The degree of ionization of the diffusing substance Signup and view all the answers

Study Notes

Fick's Law of Diffusion

Flux (J) is directly proportional to diffusivity (D) and concentration gradient (ΔC) and inversely proportional to membrane thickness (X)
J = -D ΔC/X

Factors Affecting Diffusivity

Surface area of membrane (cannot be controlled)
Molecular size (smaller molecules are better, can be controlled to a degree)
Lipophilicity/ionization (can be controlled, uncharged molecules diffuse more readily)

Ionization

Ionized molecules don't diffuse readily through lipid bilayer, uncharged molecules do
Charged molecules are "trapped" on one side of the membrane
pH influences ionization: pH < pKa (acidic environment), pH = pKa (neutral environment), pH > pKa (alkaline environment)

Ionization and pH

Acidic drugs: un-ionized in acidic medium, ionized in alkaline environment
Basic drugs: ionized in acidic medium, un-ionized in alkaline environment

Active Transport and Facilitated Diffusion

Does not care about Fick's laws or ionization
Active transport proteins can be used for uptake into the cell or efflux out of the cell
Transport expression can be induced (increased genetic expression = increased protein synthesis)

Membrane "Barriers" and Access to Organs

Hepatic blood vessels: capillaries are lined with a basement membrane broken by slit junctions (fenestrations)
Blood-brain barrier: cells have very tight junctions, active efflux mechanisms further limit penetration of polar compounds
Blood capillaries and renal glomerular membranes: porous, allow non-polar and polar molecules to pass through
Renal tubules: membranes are relatively non-porous, only drugs that are lipophilic or non-ionized can be passively reabsorbed

Pharmacokinetics: ADME

Absorption: movement of drug from site of administration to systemic circulation
Distribution: movement of drug from systemic circulation to tissues
Metabolism: biotransformation of drug
Elimination: removal of drug from the body

Routes of Administration

IV (Intravenous): rapid onset, 100% bioavailability
Oral (PO): exposure to low gastric pH, digestive enzymes, and hepatic portal circulation
Sublingual (SL): bypasses harsh GI environment, fairly rapid onset
Rectal (PR): bypasses harsh GI environment, fairly rapid onset
Subcutaneous (SC): bypasses harsh GI environment, can increase availability of poorly absorbed drugs
Intramuscular (IM): bypasses harsh GI environment, can increase availability of poorly absorbed drugs

Bioavailability

Fraction of an administered drug that reaches the systemic circulation
Only route with 100% bioavailability is IV

Active Transport Proteins: Interactions and Variations

One xenobiotic may compete with another for a ride on the transporter or may inhibit noncompetitively
Transport expression may be induced (increased genetic expression = increased protein synthesis)
Individuals may have phenotypic variation in transporter expression

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Test your knowledge on Fick's First Law of Diffusion and the factors that affect diffusivity such as membrane thickness, surface area, molecular size, and lipophilicity/ionization. Understand how ionized or hydrophilic drugs interact with tissues that have tight junctions.

Fick's First Law of Diffusion and Factors Affecting Diffusivity

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Questions and Answers

According to Fick's first law of diffusion, which factor does NOT affect the diffusivity (D) of a drug molecule?

How does the ionization of a drug molecule affect its ability to pass through a lipid bilayer membrane?

Which of the following is the LEAST likely to be affected by the ionization of a drug molecule?

A drug with a pKa of 4.4 is a weak acid. If the drug is in plasma (pH 7.4) and gastric juice (pH 1.4), how will the ionization of the drug differ between the two environments?

Which of the following is the LEAST likely to be affected by increased blood flow to the site of administration?

Which of the following is an example of facilitated diffusion, as opposed to passive diffusion?

Which of the following statements about active transport proteins is correct?

What can happen when two xenobiotics compete for the same active transport protein?

What is the consequence of the induction of active transport proteins?

Which of the following statements about the blood-brain barrier is correct?

Which of the following membranes are relatively non-porous, allowing only lipophilic or non-ionized molecules to passively diffuse across?

Which of the following statements about the hepatic blood vessels is correct?

In an acidic environment (pH < pKa), an acidic drug will be:

For a basic drug in an alkaline environment (pH > pKa), which form is more predominant?

Which transport mechanism is NOT affected by the ionization state of a drug?

In a neutral environment (pH = pKa), what is the ratio of ionized to unionized forms for an acidic drug?

Which statement is TRUE about the absorption of ionized drugs?

In the elimination process, which form of a basic drug is more likely to be excreted?

Will the transcription and translation of proteins needed for the induction of transporters occur rapidly with the first dose or over time with repeated dosing?

What is the most likely route of administration based on the information provided?

What is the half-life (t1/2) for elimination of the drug based on the given data?

What is the apparent volume of distribution (Vd) of the drug according to the calculations provided?

What is the clearance of the drug based on the information given?

Which of the following suffixes often indicates a sustained-release drug formulation?

Which of the following routes of administration is most likely to result in first-pass metabolism of a drug?

Which of the following is a potential advantage of the subcutaneous (SC) route of drug administration?

Which of the following describes a drug that exhibits zero-order elimination kinetics?

Which of the following is a characteristic of Michaelis-Menten enzyme kinetics?

What is the consequence of two xenobiotics competing for the same active transport protein?

What is the main effect of active efflux mechanisms at the blood-brain barrier?

How do smaller lipophilic molecules typically enter the brain?

In which scenario can only lipophilic or non-ionized drugs be passively reabsorbed in renal tubules?

How does induction of transport expression affect protein synthesis?

Which route of drug administration has 100% bioavailability?

According to Fick's first law of diffusion, which factor DOES affect the diffusivity (D) of a drug molecule?

In an acidic environment (pH < pKa), an acidic drug will be predominantly in which form?

Which transport mechanism is affected by the ionization state of a drug?

Which of the following is an example of zero-order elimination kinetics?

Which kinetic process is characterized by a constant fraction of the remaining drug being eliminated per unit time?

What is the primary advantage of controlled-release drug formulations over immediate-release formulations?

Which of the following statements about zero-order elimination kinetics is true?

Which of the following factors can influence the rate of hepatic drug metabolism?

What is the primary factor determining the extent of passive diffusion across a membrane for an ionized drug?

Which of the following statements about first-order elimination is correct?

Which of the following best describes the Michaelis-Menten equation in enzyme kinetics?

In the context of drug delivery, what is the purpose of sustained-release formulations?

Which of the following statements about zero-order elimination is correct?

Which of the following is a common phase I reaction in drug metabolism?

According to the information provided, if a patient drinks a large quantity of grapefruit juice (a p-glycoprotein inhibitor), the blood levels of propranolol will:

For the induction of transporters to occur, the increased transcription and translation of the necessary proteins will happen:

For a weak acid drug with a pKa of 3.5, such as aspirin, the drug will be most greatly absorbed via diffusion in the:

For a basic drug with a pKa of 7.3, which urine pH would result in a higher amount of the drug being excreted?

If two xenobiotics compete for the same active transport protein, what is the likely outcome?

Which of the following statements about first-order elimination is correct?

In enzyme kinetics, the Michaelis-Menten constant (Km) represents:

In the context of drug delivery, what is the primary advantage of zero-order elimination kinetics?

Which of the following statements about drug metabolism is correct?

Which of the following factors does NOT affect the rate of passive diffusion across a membrane?

Study Notes

Fick's Law of Diffusion

Factors Affecting Diffusivity

Ionization

Ionization and pH

Active Transport and Facilitated Diffusion

Membrane "Barriers" and Access to Organs

Pharmacokinetics: ADME

Routes of Administration

Bioavailability

Active Transport Proteins: Interactions and Variations

Studying That Suits You

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