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?

It only metabolizes exogenous substances. Signup and view all the answers

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

The specific isozyme within the subfamily Signup and view all the answers

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

Absorption Signup and view all the answers

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

Surface area Signup and view all the answers

In pharmacokinetics, which phase follows absorption?

Distribution Signup and view all the answers

Which organ is primarily responsible for the biotransformation of drugs?

Liver Signup and view all the answers

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

Excretion Signup and view all the answers

Which is NOT a mechanism that controls drug absorption?

Drug interaction Signup and view all the answers

Which of the following factors can alter drug metabolism pathways?

Genetics Signup and view all the answers

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

Half-life Signup and view all the answers

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

It accelerates drug metabolism. Signup and view all the answers

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

Ketoconazole Signup and view all the answers

How does enzyme inhibition affect drug levels in the body?

It leads to increased drug levels, possibly causing toxicity. Signup and view all the answers

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

Decreased therapeutic effects. Signup and view all the answers

What describes the time course for maximal enzyme induction effect?

Typically takes several days to weeks. Signup and view all the answers

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

Both induction and inhibition can lead to drug interactions. Signup and view all the answers

What is a common clinical significance of enzyme inhibition?

It can necessitate dose reductions to prevent toxicity. Signup and view all the answers

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

It inhibits CYP450 enzymes in the gut. Signup and view all the answers

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

Concentration gradient Signup and view all the answers

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

They have large, discontinuous capillaries. Signup and view all the answers

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

Increased lipid solubility Signup and view all the answers

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

Low blood flow at absorption site Signup and view all the answers

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

Dissolution in the membrane Signup and view all the answers

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

Transport rate is directly proportional to concentration gradient. Signup and view all the answers

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

Alcohol and water Signup and view all the answers

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

Its lipophilic properties Signup and view all the answers

What is the primary organ responsible for drug metabolism?

Liver Signup and view all the answers

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

Oral formulations require a larger dose than IV formulations. Signup and view all the answers

Which phase of drug metabolism involves oxidation and reduction reactions?

Phase I Signup and view all the answers

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

Phase II reactions Signup and view all the answers

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

To metabolize drugs during Phase I reactions Signup and view all the answers

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

It becomes an active drug Signup and view all the answers

How do conjugation reactions in Phase II metabolism affect drugs?

They enhance their water solubility Signup and view all the answers

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

Conversion of drugs into metabolites for excretion Signup and view all the answers

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

Tight junctions between endothelial cells Signup and view all the answers

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

Lipophilic drugs Signup and view all the answers

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

Can make it become porous Signup and view all the answers

How does intrathecal drug delivery differ from traditional methods?

It bypasses the Blood-Brain Barrier directly Signup and view all the answers

What is a primary effect of aging on drug absorption?

Decreased GI motility Signup and view all the answers

Why might hydrophilic drugs have difficulty penetrating the CNS?

They do not utilize transport proteins effectively Signup and view all the answers

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

Smaller skeletal muscle mass Signup and view all the answers

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

Blood-Brain Barrier Signup and view all the answers

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.