Podcast
Questions and Answers
According to Fick's first law of diffusion, which factor does NOT affect the diffusivity (D) of a drug molecule?
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?
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?
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?
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 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 is an example of facilitated diffusion, as opposed to passive diffusion?
Which of the following statements about active transport proteins is correct?
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 can happen when two xenobiotics compete for the same active transport protein?
What is the consequence of the induction of active transport proteins?
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 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 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?
Which of the following statements about the hepatic blood vessels is correct?
In an acidic environment (pH < pKa), an acidic drug will be:
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?
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?
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?
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?
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?
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?
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 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 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 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?
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 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 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 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 describes a drug that exhibits zero-order elimination kinetics?
Which of the following is a characteristic of Michaelis-Menten enzyme 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 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?
What is the main effect of active efflux mechanisms at the blood-brain barrier?
How do smaller lipophilic molecules typically enter the brain?
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?
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?
How does induction of transport expression affect protein synthesis?
Which route of drug administration has 100% bioavailability?
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?
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?
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 transport mechanism is affected by the ionization state of a drug?
Which of the following is an example of zero-order elimination kinetics?
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?
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?
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 statements about zero-order elimination kinetics is true?
Which of the following factors can influence the rate of hepatic drug metabolism?
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?
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 statements about first-order elimination is correct?
Which of the following best describes the Michaelis-Menten equation in enzyme kinetics?
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?
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 statements about zero-order elimination is correct?
Which of the following is a common phase I reaction in drug metabolism?
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:
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 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 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?
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?
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?
Which of the following statements about first-order elimination is correct?
In enzyme kinetics, the Michaelis-Menten constant (Km) represents:
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?
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 statements about drug metabolism is correct?
Which of the following factors does NOT affect the rate of passive diffusion across a membrane?
Which of the following factors does NOT affect the rate of passive diffusion across a membrane?
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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Description
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.
