Podcast
Questions and Answers
What is the primary advantage of IV administration of drugs?
What is the primary advantage of IV administration of drugs?
Which factor has the greatest influence on the volume of distribution of a drug?
Which factor has the greatest influence on the volume of distribution of a drug?
In what scenario is IV administration considered the best option?
In what scenario is IV administration considered the best option?
What potential risk is associated with IV drug administration?
What potential risk is associated with IV drug administration?
Signup and view all the answers
How do drug molecules move from the bloodstream into tissues?
How do drug molecules move from the bloodstream into tissues?
Signup and view all the answers
What is the primary significance of the Volume of Distribution (Vd) in pharmacokinetics?
What is the primary significance of the Volume of Distribution (Vd) in pharmacokinetics?
Signup and view all the answers
How is the Volume of Distribution (Vd) mathematically calculated?
How is the Volume of Distribution (Vd) mathematically calculated?
Signup and view all the answers
What does the calculation of Volume of Distribution assume about the drug's concentration in tissues?
What does the calculation of Volume of Distribution assume about the drug's concentration in tissues?
Signup and view all the answers
If a drug has a Volume of Distribution (Vd) significantly higher than the total body water, what does this indicate?
If a drug has a Volume of Distribution (Vd) significantly higher than the total body water, what does this indicate?
Signup and view all the answers
What other pharmacokinetic aspects can be estimated with the Volume of Distribution (Vd)?
What other pharmacokinetic aspects can be estimated with the Volume of Distribution (Vd)?
Signup and view all the answers
How does protein binding affect the distribution of drugs in the body?
How does protein binding affect the distribution of drugs in the body?
Signup and view all the answers
What happens to the volume of distribution (Vd) as protein binding increases?
What happens to the volume of distribution (Vd) as protein binding increases?
Signup and view all the answers
Which factor does NOT influence the extent of protein binding?
Which factor does NOT influence the extent of protein binding?
Signup and view all the answers
What effect does a decrease in protein binding have on drug concentration?
What effect does a decrease in protein binding have on drug concentration?
Signup and view all the answers
How does the lipid solubility of a drug relate to protein binding?
How does the lipid solubility of a drug relate to protein binding?
Signup and view all the answers
What is a consequence of increased free unbound drug concentration?
What is a consequence of increased free unbound drug concentration?
Signup and view all the answers
Which scenario may affect plasma protein concentration?
Which scenario may affect plasma protein concentration?
Signup and view all the answers
How is the salt form of a drug typically named?
How is the salt form of a drug typically named?
Signup and view all the answers
What defines the interaction of drugs with plasma proteins?
What defines the interaction of drugs with plasma proteins?
Signup and view all the answers
Which of the following drugs is a salt of a weak acid?
Which of the following drugs is a salt of a weak acid?
Signup and view all the answers
What is true about weak bases in their interaction with hydrogen ions?
What is true about weak bases in their interaction with hydrogen ions?
Signup and view all the answers
What does the pKa value represent?
What does the pKa value represent?
Signup and view all the answers
In the Henderson-Hasselbalch equation, what does a higher pH indicate for weak acids?
In the Henderson-Hasselbalch equation, what does a higher pH indicate for weak acids?
Signup and view all the answers
What is the characteristic of the nonionized form of a drug?
What is the characteristic of the nonionized form of a drug?
Signup and view all the answers
Which pair of drugs are exceptions where you cannot determine if they are acids or bases from their names?
Which pair of drugs are exceptions where you cannot determine if they are acids or bases from their names?
Signup and view all the answers
What happens to weak acid drugs as the pH decreases?
What happens to weak acid drugs as the pH decreases?
Signup and view all the answers
At a physiologic pH of 7.4, how will Acetylsalicylic acid, a weak acid with a pKa of 3.5, primarily exist?
At a physiologic pH of 7.4, how will Acetylsalicylic acid, a weak acid with a pKa of 3.5, primarily exist?
Signup and view all the answers
What effect does increasing pH have on weak base drugs?
What effect does increasing pH have on weak base drugs?
Signup and view all the answers
What is the primary effect of ion trapping on drug absorption?
What is the primary effect of ion trapping on drug absorption?
Signup and view all the answers
How does the concentration of a weak acid drug differ across a membrane that separates fluids of different pH levels?
How does the concentration of a weak acid drug differ across a membrane that separates fluids of different pH levels?
Signup and view all the answers
In the stomach, what is the ionization ratio of a weak acid drug with a pKa of 4.4?
In the stomach, what is the ionization ratio of a weak acid drug with a pKa of 4.4?
Signup and view all the answers
Which of the following statements about weak acids and weak bases is true?
Which of the following statements about weak acids and weak bases is true?
Signup and view all the answers
What characteristic affects the ability of nonionized drugs to cross cell membranes?
What characteristic affects the ability of nonionized drugs to cross cell membranes?
Signup and view all the answers
What is the result of local anesthetics being trapped in the fetus?
What is the result of local anesthetics being trapped in the fetus?
Signup and view all the answers
How does urinary pH alteration affect the excretion of weak acids and weak bases?
How does urinary pH alteration affect the excretion of weak acids and weak bases?
Signup and view all the answers
What does bioavailability measure regarding a drug?
What does bioavailability measure regarding a drug?
Signup and view all the answers
What is the primary effect of the first-pass hepatic effect on medications?
What is the primary effect of the first-pass hepatic effect on medications?
Signup and view all the answers
Which route of administration guarantees 100% bioavailability?
Which route of administration guarantees 100% bioavailability?
Signup and view all the answers
In which scenario would maternal alkalosis most likely facilitate trapping of local anesthetics in the fetus?
In which scenario would maternal alkalosis most likely facilitate trapping of local anesthetics in the fetus?
Signup and view all the answers
Which pharmacokinetic factor affects the choice of drug administration route?
Which pharmacokinetic factor affects the choice of drug administration route?
Signup and view all the answers
How do weak bases behave in acidic urine?
How do weak bases behave in acidic urine?
Signup and view all the answers
Which of the following is NOT a route of administration that affects drug bioavailability?
Which of the following is NOT a route of administration that affects drug bioavailability?
Signup and view all the answers
What occurs to lipid-soluble nonionized local anesthetics after crossing the placenta?
What occurs to lipid-soluble nonionized local anesthetics after crossing the placenta?
Signup and view all the answers
Study Notes
Introduction to Pharmacokinetics
- Pharmacokinetics is the quantitative study of how drugs are absorbed, distributed, metabolized, and excreted (ADME) by the body.
- This process determines the drug concentration at the site of action.
- It is crucial for understanding drug efficacy and toxicity.
Objectives
- Review the concept of pharmacokinetics
- Examine specific pharmacokinetic parameters
- Review pharmacokinetic rates of drug reactions
- Understand different types of pharmacokinetics
- Evaluate pharmacokinetic parameters in the context of anesthesia
- Review compartmental modeling
Pharmacokinetics
- The quantitative study of the drug's absorption, distribution, metabolism, and excretion.
- Describes how the body affects the dosage of a drug.
- Focuses on the relationship between drug dose and drug concentration in the plasma or at the site of action.
Pharmacokinetic Measurements/Concepts
- Bioavailability: The fraction of the administered dose that reaches the systemic circulation.
- Volume of distribution (Vd): A theoretical volume that reflects the apparent distribution of a drug in the body.
- Clearance (Cl): The volume of plasma cleared of a drug per unit of time.
- Elimination half-life: The time it takes for the drug concentration to decrease by 50%.
- Context-sensitive half-time (t1/2): The time it takes for the plasma concentration of a drug given by continuous infusion to decrease by 50% after stopping the infusion. It is more relevant to continuous drug infusions like those used in anesthesia..
- Effect-site equilibration time: The time required for the drug to reach equilibrium at the site of action in the body.
Absorption
- Absorption is the passage of drug molecules throughout physiological barriers before reaching systemic circulation.
- Critical for extravascular administration (e.g., oral, intramuscular).
- Factors affecting absorption include the drug's chemical structure, drug form, drug release system, anatomical site, and physiological functions.
- Passive diffusion is the main process for drug absorption when there’s a concentration gradient. Passive diffusion does not require energy.
- Factors influencing passive diffusion include membrane surface area, membrane thickness, diffusion coefficient, concentration gradient, and blood flow rate.
- Active transport and facilitated diffusion are also mechanisms for absorption, using proteins and requiring energy when needed.
Ionization
- Many anesthetic drugs are weak acids or bases, existing in both ionized and nonionized forms in the body.
- The degree of ionization depends on the pH and pKa.
- Ionized form generally is not permeable to cell membranes.
- The Henderson-Hasselbalch equation is used to predict the degree of ionization.
Characteristics of Nonionized and Ionized Drug Molecules
Feature | Nonionized | Ionized |
---|---|---|
Pharmacological Effect | Active | Inactive |
Solubility | Lipid | Water |
Cross lipid barriers | Yes | No |
Renal excretion | No | Yes |
Hepatic metabolism | Yes | No |
Identifying Weak Acids and Weak Bases
- Weak acids donate hydrogen ions.
- Weak bases accept hydrogen ions.
- The cation or anion prefixes in drug names (e.g., "sodium," "chloride") indicate whether they are weak acids or bases.
The Henderson-Hasselbalch Equation
- The equation relates pH to pKa, determining ionization.
- A drug's ionization affects its ability to cross membranes, affecting absorption and onset of action.
Effect of pH and pKa on Drug Absorption and Distribution
- The pH of the environment affects the ionization state of a drug, which impacts its ability to cross cell membranes and penetrate tissues.
- Acidic environment favors nonionized drug.
- Alkaline environment favors ionized drug.
- Changes in pH can significantly affect drug absorption, distribution, and ultimately clinical response.
Calculations of Volume of Distribution (Vd)
- V=Dose / Concentration
- This provides a representation of the drug distribution in the body.
- This is used for estimations, not precise measurements.
Protein Binding
- Protein binding affects distribution.
- Only unbound (free) drug can cross membranes.
- Highly protein-bound drugs have a lower Vd.
- Protein binding affects drug clearance.
Metabolism
- Biotransformation, the chemical conversion of a drug.
- The primary result is the conversion to water soluble metabolites, enhancing elimination.
- Liver is the primary organ for drug metabolism using mainly CYP450 enzymes.
Pathways of Drug Metabolism
- Phase I functionalization reactions introduce functional groups, increasing polarity.
- Phase II conjugation reactions modify the structure to further enhance water solubility and facilitate excretion.
CYP 450 System
- Important enzymes for drug metabolism often located in the liver.
- Inhibitors and inducers can cause significant drug-drug interactions
Excretion
- The removal of drug and metabolites from the body.
- Kidney is typically the primary excretion organ.
- Factors like pH and drug polarity affect excretion.
- Elimination is typically through renal excretion (glomerular filtration, active tubular secretion, and passive tubular reabsorption), biliary excretion, or pulmonary (exhalation).
- Other organs can be involved in metabolism.
Clearance
- Drug elimination determined by clearance (CL), which is the rate of removal of a drug.
- Clearance depends on metabolic and excretory processes.
- Clearance depends on hepatic blood flow and hepatic extraction ratio (ER).
- Clearance is primarily determined by the liver for those drugs metabolized there.
- Higher extraction ratio for the liver indicates hepatic clearance is dependent on the blood flow to the liver, influencing how much drug is extracted.
Hepatic Clearance
- Affected by hepatic blood flow, drug binding, hepatic enzyme activity.
- High hepatic extraction ratio drugs are mostly affected by hepatic blood flow (flow rate limiting).
- Low hepatic extraction ratio drugs are mostly affected by hepatic enzyme activity.
Renal Clearance
- Primarily responsible for water soluble drugs.
- Glomerular filtration, active tubular secretion, and passive tubular reabsorption.
- Acidic urine favors excretion of weak bases; alkaline urine favors excretion of weak acids.
Biliary Excretion
- Transfer of drug and metabolites via hepatocytes to the bile.
- Drugs excreted in the bile can be reabsorbed.
- Enterohepatic recirculation prolongs the duration of action
Enterohepatic Circulation
- Cycle of drug/metabolite excretion, reabsorption from the GI tract, and re-excretion.
Compartmental Models
- Used for drug distribution and elimination in the body.
- One-compartment model: Drug distributes uniformly and clearance is constant.
- Multi-compartment model: Drug distribution involves several body compartments with variable transfer rates.; useful for understanding how drugs distribute and are eliminated more efficiently.
- Two-compartment and three-compartment Models: Two or three distinct tissue compartments.
One-Compartment Model
- Assumes instant equilibrium, first-order elimination.
Multi-Compartment Model
- Describes drug distribution/elimination through multiple compartments.
Redistribution
- Movement of drug from highly perfused tissue to less perfused tissue (e.g., muscle).
- This can affect duration of drug action.
Rate & Capacity of Tissue Uptake of Drugs
- Affected by various factors that influence tissue uptake.
Elimination Half-Life
- Time to reach 50% of concentration after absorption and distribution phase.
- Influenced by volume of distribution and clearance.
Steady-State
- Achieved when administration rate = elimination rate.
- Plasma concentrations remain constant (or relatively so).
Context-Sensitive Half-Time
- Time to reach 50% of plasma concentration decrease after stopping a continuous infusion.
- Useful in anesthesia.
- Takes into account the combined effects of distribution, metabolism, and infusion duration.
Zero-Order Kinetics
- Constant amount of drug eliminated per unit time; enzymes are saturated.
First-Order Kinetics
- Constant percentage of drug eliminated per unit time.
Studying That Suits You
Use AI to generate personalized quizzes and flashcards to suit your learning preferences.
Related Documents
Description
Test your knowledge on pharmacokinetics, focusing on the Volume of Distribution (Vd) and IV drug administration. This quiz explores key concepts such as the advantages of IV administration, how drug molecules distribute in the body, and the significance of Vd calculations in pharmacology. Challenge yourself to understand the factors that influence drug distribution and risks associated with IV administration.