Pharmacokinetics: Drug Absorption and Elimination
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Questions and Answers

What is the primary function of Phase I reactions in drug metabolism?

  • Eliminate toxic substances from the body
  • Convert polar drugs into lipophilic molecules
  • Introduce polar functional groups to lipophilic drugs (correct)
  • Increase the pharmacologic activity of all drugs

Which cytochrome P450 subfamily is commonly involved in drug metabolism?

  • CYP2D
  • CYP3A (correct)
  • CYP4E
  • CYP1A

What factors can Phase I metabolism influence regarding pharmacologic activity?

  • It can only increase pharmacologic activity.
  • It can have no effect on pharmacologic activity.
  • It can decrease pharmacologic activity only.
  • It can increase, decrease, or have no effect on pharmacologic activity. (correct)

Which of the following is NOT a characteristic of the cytochrome P450 system?

<p>It only metabolizes exogenous substances. (D)</p> Signup and view all the answers

What does the number following the 'CYP' designation indicate?

<p>The specific isozyme within the subfamily (B)</p> Signup and view all the answers

Which process occurs after drug administration and allows the drug to enter the bloodstream?

<p>Absorption (D)</p> Signup and view all the answers

What property of the administration site significantly affects the rate of drug absorption?

<p>Surface area (A)</p> Signup and view all the answers

In pharmacokinetics, which phase follows absorption?

<p>Distribution (A)</p> Signup and view all the answers

Which organ is primarily responsible for the biotransformation of drugs?

<p>Liver (D)</p> Signup and view all the answers

What is the term for the elimination of drugs from the body through urine, bile, or feces?

<p>Excretion (A)</p> Signup and view all the answers

Which is NOT a mechanism that controls drug absorption?

<p>Drug interaction (D)</p> Signup and view all the answers

Which of the following factors can alter drug metabolism pathways?

<p>Genetics (D)</p> Signup and view all the answers

Which parameter indicates how quickly a drug is eliminated from the body?

<p>Half-life (C)</p> Signup and view all the answers

What is the primary effect of enzyme induction on drug metabolism?

<p>It accelerates drug metabolism. (B)</p> Signup and view all the answers

Which of the following is NOT an example of a CYP450 enzyme inducer?

<p>Ketoconazole (B)</p> Signup and view all the answers

How does enzyme inhibition affect drug levels in the body?

<p>It leads to increased drug levels, possibly causing toxicity. (D)</p> Signup and view all the answers

What kind of drug action can result from the induction of CYP450 enzymes?

<p>Decreased therapeutic effects. (C)</p> Signup and view all the answers

What describes the time course for maximal enzyme induction effect?

<p>Typically takes several days to weeks. (A)</p> Signup and view all the answers

Which of the following accurately describes the potential for drug interactions?

<p>Both induction and inhibition can lead to drug interactions. (A)</p> Signup and view all the answers

What is a common clinical significance of enzyme inhibition?

<p>It can necessitate dose reductions to prevent toxicity. (A)</p> Signup and view all the answers

Which factor is true regarding the effect of grapefruit juice on drug metabolism?

<p>It inhibits CYP450 enzymes in the gut. (C)</p> Signup and view all the answers

What factor primarily affects the absorption of drugs through capillary walls?

<p>Concentration gradient (A)</p> Signup and view all the answers

Why are the capillaries in the liver and kidneys described as more porous?

<p>They have large, discontinuous capillaries. (D)</p> Signup and view all the answers

What characteristic of a drug increases its absorption through the cell membrane?

<p>Increased lipid solubility (C)</p> Signup and view all the answers

Which of the following factors is NOT likely to increase drug absorption?

<p>Low blood flow at absorption site (A)</p> Signup and view all the answers

Which method does passive diffusion utilize for drug transport across cell membranes?

<p>Dissolution in the membrane (C)</p> Signup and view all the answers

What is the relationship between the concentration gradient and transport rate according to Fick’s law?

<p>Transport rate is directly proportional to concentration gradient. (A)</p> Signup and view all the answers

Which small hydrophilic molecules are easily absorbed by the cell membrane?

<p>Alcohol and water (B)</p> Signup and view all the answers

What contributes to the enhanced absorption of aspirin in the digestive system?

<p>Its lipophilic properties (B)</p> Signup and view all the answers

What is the primary organ responsible for drug metabolism?

<p>Liver (C)</p> Signup and view all the answers

What is the impact of first-pass metabolism on drug dosage?

<p>Oral formulations require a larger dose than IV formulations. (D)</p> Signup and view all the answers

Which phase of drug metabolism involves oxidation and reduction reactions?

<p>Phase I (D)</p> Signup and view all the answers

Which type of drug biotransformation can convert an active drug into an inactive form?

<p>Phase II reactions (B)</p> Signup and view all the answers

What is the function of cytochrome P450 enzymes in drug metabolism?

<p>To metabolize drugs during Phase I reactions (C)</p> Signup and view all the answers

Which outcome can result from the conversion of an inactive prodrug?

<p>It becomes an active drug (C)</p> Signup and view all the answers

How do conjugation reactions in Phase II metabolism affect drugs?

<p>They enhance their water solubility (C)</p> Signup and view all the answers

What is the result of drug metabolism conducted by the Drug Microsomal Metabolizing System (DMMS)?

<p>Conversion of drugs into metabolites for excretion (B)</p> Signup and view all the answers

What primarily restricts the passage of substances through the Blood-Brain Barrier?

<p>Tight junctions between endothelial cells (D)</p> Signup and view all the answers

Which type of drugs can cross the Blood-Brain Barrier most readily?

<p>Lipophilic drugs (B)</p> Signup and view all the answers

What effect does inflammation have on the Blood-Brain Barrier?

<p>Can make it become porous (D)</p> Signup and view all the answers

How does intrathecal drug delivery differ from traditional methods?

<p>It bypasses the Blood-Brain Barrier directly (C)</p> Signup and view all the answers

What is a primary effect of aging on drug absorption?

<p>Decreased GI motility (D)</p> Signup and view all the answers

Why might hydrophilic drugs have difficulty penetrating the CNS?

<p>They do not utilize transport proteins effectively (C)</p> Signup and view all the answers

Which of the following best describes the physical characteristics of neonates that affect drug absorption?

<p>Smaller skeletal muscle mass (A)</p> Signup and view all the answers

Mannitol is an example of a substance that can influence the permeability of which barrier?

<p>Blood-Brain Barrier (B)</p> Signup and view all the answers

Flashcards

Drug Absorption

The movement of a drug from its administration site into the bloodstream.

Barriers to Absorption

The physical barriers that a drug must pass through to be absorbed, including cell membranes, capillary walls, and specialized barriers like the blood-brain barrier and the placenta.

Surface Area of Absorption Site

The rate at which a drug is absorbed is influenced by several factors, including the surface area of the absorption site. A larger surface area means more potential for absorption.

What is Pharmacokinetics?

Pharmacokinetics refers to the study of how the body affects a drug, including absorption, distribution, metabolism, and elimination.

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Drug Metabolism

The process by which a drug is broken down or transformed by the body, usually in the liver.

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Drug Elimination

The removal of a drug and its metabolites from the body, typically through urine, feces, or bile.

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Half-Life

The amount of time it takes for the concentration of a drug in the body to decrease by half.

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Drug Clearance

The rate at which a drug is removed from the body.

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What is the Blood-Brain Barrier (BBB)?

A selective barrier between the bloodstream and the central nervous system (CNS) that controls which substances can enter the brain.

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What do tight junctions do in the BBB?

Tight junctions between endothelial cells of the blood vessels in the brain, preventing large hydrophilic molecules from easily crossing.

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How can the BBB become more porous?

Inflammation and hypertonic solutions (like mannitol) can make the BBB more permeable, allowing more substances to enter the brain.

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How do drugs cross the BBB?

Drugs must be small and hydrophobic (fat-soluble) to easily pass through the BBB, or utilize specific transport proteins to enter the brain.

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Why do hydrophilic drugs have difficulty crossing the BBB?

Hydrophilic drugs that don't use transport proteins will struggle to enter the CNS. This means they're less likely to reach their target in the brain.

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How does lipophilicity affect drug penetration into the CNS?

Lipophilic drugs, like propofol, can cross the BBB more easily because they can dissolve in the fatty membranes.

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What is intrathecal drug delivery?

In intrathecal delivery, drugs are administered directly into the cerebrospinal fluid (CSF), bypassing the BBB.

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When is intrathecal drug delivery used?

Intrathecal delivery is used for certain conditions like meningitis or spinal anesthesia, but it's not practical for regular drug administration.

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Liver

The primary organ responsible for drug metabolism.

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Drug Metabolizing Enzymes

Specialized proteins within liver cells that break down drugs. They are essential for drug metabolism.

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Phase I Metabolism

The first step in drug metabolism involving reactions like oxidation and reduction. It often converts drugs into more polar and water-soluble forms.

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Phase II Metabolism

The second step in drug metabolism involving reactions like conjugation. It adds molecules to drugs, further increasing their water solubility, making them easier to excrete.

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Drug Microsomal Metabolizing System (DMMS)

A group of enzymes, mainly cytochrome P450 enzymes, located in the liver. They play a vital role in oxidizing and reducing drugs and other substances.

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First-Pass Effect

The initial passage of a drug through the liver before reaching systemic circulation. This can significantly reduce the drug's bioavailability.

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Bioavailability

The amount of a drug that reaches systemic circulation and has the potential to exert its therapeutic effect. It can be significantly affected by first-pass metabolism.

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What do Phase I reactions do?

Phase I reactions modify drugs' chemical structure to make them more water-soluble, helping them get excreted from the body.

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What is the CYP system?

The cytochrome P450 (CYP) system is a group of enzymes that mainly break down drugs and other substances in the liver and gut.

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What's the difference between lipophilic and polar molecules?

Lipophilic drugs are fat-soluble, while polar molecules are water-soluble. Phase I reactions make lipophilic drugs more polar.

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How do Phase I reactions make drugs more polar?

They introduce a polar functional group, like -OH or -NH2.

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What does the CYP system do besides breaking down drugs?

The CYP system is crucial for metabolizing many natural compounds in the body, like steroids and lipids.

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Concentration Gradient

The difference in concentration of a drug between two areas, driving its movement from high to low concentration.

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Fick's Law

The rate of drug absorption is directly proportional to the difference in concentration between the absorption site and the blood.

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Capillaries

Tiny blood vessels that allow exchange of materials, like drugs, between blood and cells.

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Lipid Solubility

The ability of a drug to dissolve in fats or oils.

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Un-ionized Drug

A drug molecule that is not charged, making it easier to cross cell membranes.

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Drug Formations

Various forms of a drug, from large crystals to microscopic particles, affecting how fast it dissolves and absorbs.

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Cell Membrane Permeability

The ability of a drug to cross membranes depends on its lipid solubility and whether it is un-ionized.

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CYP P450 Induction and Inhibition

CYP P450 enzymes are a family of enzymes that help metabolize many drugs. Enzyme induction increases the synthesis of these enzymes, making the body metabolize drugs faster. Enzyme inhibition decreases the activity of these enzymes, slowing down drug metabolism.

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Enzyme Induction Impact

Increased synthesis of CYP450 enzymes leads to faster drug metabolism, lower drug levels in the body, and potentially reduced effectiveness or shorter duration of action.

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Enzyme Inhibition Impact

Decreased activity of CYP450 enzymes leads to slower drug metabolism, higher drug levels in the body, potentially increased effects, prolonged duration of action, or toxicity.

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Enzyme Inducers

Examples of enzyme inducers include rifampin, carbamazepine, and phenobarbital. These drugs can increase the metabolism of other drugs, potentially requiring dose adjustments.

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Enzyme Inhibitors

Examples of enzyme inhibitors include ketoconazole, ritonavir, and grapefruit juice. These drugs can slow down the metabolism of other drugs, potentially requiring dose adjustments or leading to drug interactions.

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Induction and Inhibition Time Course

Induction takes several days to weeks to reach its maximum effect, while inhibition can occur rapidly, within hours to a few days.

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Clinical Significance of Induction/Inhibition

Dose adjustments of drugs affected by enzyme induction or inhibition are crucial to maintain therapeutic effect or avoid toxicity.

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Drug Interaction

Induction and inhibition can lead to drug interactions, as one drug can affect the metabolism of another.

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Study Notes

Kinetics of Drug Absorption and Elimination

  • Pharmacokinetics describes the effects of biological systems on drugs.
  • Major processes in pharmacokinetics are absorption, distribution, metabolism, and elimination.
  • Absorption: The drug enters the bloodstream directly or indirectly from the administration site.
  • Distribution: The drug leaves the bloodstream and distributes into interstitial and intracellular fluids.
  • Metabolism: The liver or other tissues chemically change the drug.
  • Elimination: The drug and its metabolites exit the body in urine, bile, or feces.

Learning Objectives

  • List and describe the advantages and disadvantages of different drug administration routes.
  • Detail the mechanisms that affect drug absorption.
  • Define the properties of drugs that govern absorption, distribution, and excretion.
  • Graphically illustrate the differences between zero-order and first-order kinetics.
  • Define pharmacokinetic parameters including half-life, clearance, and volume of distribution.
  • List major drug metabolism pathways and factors altering them (e.g., age, genetics, disease states).
  • Describe the major sites and mechanisms of drug elimination.
  • Describe disease states altering elimination kinetics.

Drug Absorption

  • Drug absorption is the movement of a drug into the bloodstream after administration.
  • Absorption is controlled by cell membranes, capillary walls, and barriers like the blood-brain barrier and placenta.
  • Factors affecting absorption rate: Surface area of the absorption site, blood flow at the site, concentration gradient, drug formation (crystal size), lipid solubility, and ionization state.

Drug Absorption: Capillary Walls

  • Capillaries are the sites where materials are exchanged between blood and cells.
  • Capillary walls are thin (one cell thick).
  • Pores in the walls allow ions, water, nutrients, and unbound drugs to move in and out.
  • Capillaries in the liver and kidneys are more porous and allow larger plasma proteins to pass through.

Drug Absorption: Cell Membrane

  • Cell membranes are permeable to many drug molecules, but permeability depends on lipid solubility.
  • Small aqueous pores and channels allow entry of small hydrophilic molecules (e.g., alcohol, water).
  • Passive diffusion: Lipophilic molecules diffuse through the lipid cell membrane; rate proportional to the concentration gradient.
  • Carrier-mediated transport: Active transport against a concentration gradient, facilitated by carrier proteins which bind specific molecules.
  • Endocytosis: Used for large molecules that cannot cross the membrane by diffusion or carrier transport.

Blood-Brain Barrier (BBB)

  • The BBB protects the brain from foreign substances.
  • The BBB is a selective barrier between circulating blood and the central nervous system (CNS).
  • Its capillaries have tight junctions that restrict the passage of large hydrophilic molecules.
  • Inflammation and hypertonic solutions can make the BBB porous, allowing more drugs to enter the brain.
  • Drugs must be either small and hydrophobic or use existing transport proteins to reach the CNS.

Neonates vs. Aging on Drug Absorption

  • Neonates/Infants: Smaller muscle mass, thinner skin, and less acidic gastrointestinal tract can lead to a slower absorption rate after intramuscular injections and quicker absorption after topical application.
  • Aging: Decreased intestinal surface area, blood flow, gastrointestinal motility, and onset of action affect drug absorption.

Drug Distribution

  • Drug distribution is the process of a drug leaving the bloodstream and entering extracellular fluid and tissues.
  • Factors affecting distribution: Blood flow, blood-brain barrier, and plasma protein binding.
  • The brain has significant blood supply, so drugs rapidly enter.
  • Drugs highly bound to plasma proteins have limited distribution to tissues.

Volume of Distribution (Vd)

  • Vd is the ratio of drug amount in the body to drug concentration in the blood/plasma.
  • High Vd suggests significant tissue distribution; low Vd suggests primarily plasma presence
  • Important in determining the correct dose and understanding drug distribution within the body.
  • Factors influencing Vd: Body composition, age, gender, disease states, lipophilicity, plasma protein binding, and molecular size.

Drug Metabolism

  • Metabolism is the chemical alteration of drugs in the body, often by enzymes in the liver.
  • Phase I reactions (oxidation, reduction, or hydrolysis) convert drugs into more water-soluble forms.
  • Phase II reactions involve conjugation, adding a functional group to increase water solubility and facilitate excretion.
  • The cytochrome P450 (CYP) system plays a crucial role in drug metabolism (Phase I). The efficiency of CYP 450 can be affected by various factors including inducers and inhibitors, leading to altered drug metabolism.

Drug Metabolism: Phase II Conjugation

  • Phase 2 reacts involve conjugation, and add a polar functional group.
  • Examples of conjugation reactions: Glucuronidation, acetylation, and sulfation. These reactions allow drugs to be excreted more efficiently.

CYP450 Enzyme Induction and Inhibition

  • CYP450 enzymes are involved in drug metabolism.
  • Enzyme induction increases CYP450 activity, speeding up drug metabolism, potentially decreasing drug effect.
  • Enzyme inhibition reduces CYP450 activity, slowing down drug metabolism, potentially increasing drug effect.
  • Examples of inducers (increase metabolism) and inhibitors (decrease metabolism) include specific drugs and substances like St. John's Wort, grapefruit juice etc.

Drug Metabolism in Neonates/Infants and Aging

  • Neonates/Infants: Have lower capacity for drug metabolism, leading to slower elimination and prolonged drug effects.
  • Aging: Decreased rate of metabolism related to age-related decreases in liver blood flow and diminished cardiac output cause drug metabolism to occur slower.

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Description

This quiz focuses on the kinetics of drug absorption and elimination, detailing key processes in pharmacokinetics such as absorption, distribution, metabolism, and elimination. Participants will explore the advantages and disadvantages of various drug administration routes, and understand the pharmacokinetic parameters that influence drug behavior in the body.

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