FACTOID # 7: The top five best educated states are all in the Northeast.
 
 Home   Encyclopedia   Statistics   States A-Z   Flags   Maps   FAQ   About 
 
WHAT'S NEW
 

SEARCH ALL

FACTS & STATISTICS    Advanced view

Search encyclopedia, statistics and forums:

 

 

(* = Graphable)

 

 


Encyclopedia > Drug metabolism

Drug metabolism is the metabolism of drugs, their biochemical modification or degradation, usually through specialized enzymatic systems. Drug metabolism often converts lipophilic chemical compounds into more readily excreted polar products. Its rate is an important determinant of the duration and intensity of the pharmacological action of drugs. Santorio Santorio (1561-1636) in his steelyard balance, from Ars de statica medecina, first published 1614 Metabolism (from μεταβολισμος (metabolismos)) is the biochemical modification of chemical compounds in living organisms anggjgjhnd cell (b). ... Oral medication A medication is a licenced drug taken to cure or reduce symptoms of an illness or medical condition. ... Biochemistry is the chemistry of life. ... Ribbon diagram of the enzyme TIM. TIM is catalytically perfect, meaning its conversion rate is limited, or nearly limited to its substrate diffusion rate. ... In chemistry, hydrophobic or lipophilic species, or hydrophobes, tend to be electrically neutral and nonpolar, and thus prefer other neutral and nonpolar solvents or molecular environments. ... A chemical compound is a chemical substance formed from two or more elements, with a fixed ratio determining the composition. ... Excretion is the biological process by which an organism chemically separates waste products from its body. ... The adjective hydrophilic describes something that likes water (from Greek hydros = water; philos = friend). ...


Drug metabolism can result in toxication or detoxication - the activation or deactivation of the chemical. While both occur, the major metabolites of most drugs are detoxication products. Oral medication A medication is a licenced drug taken to cure or reduce symptoms of an illness or medical condition. ... Toxication is the process of drug metabolism in which the metabolite of a compound is more toxic than the parent drug or chemical. ... The major metabolites formed from most drug metabolism are detoxication products. ...


Drugs are almost all xenobiotics. Other commonly used organic chemicals are also drugs, and are metabolized by the same enzymes as drugs. This provides the opportunity for drug-drug and drug-chemical interactions or reactions. A xenobiotic is a chemical which is found in an organism but which is not normally produced or expected to be present in it. ... An organic compound is any of a large class of chemical compounds whose molecules contain carbon, with exception of carbides, carbonates and carbon oxides. ... Ribbon diagram of the enzyme TIM. TIM is catalytically perfect, meaning its conversion rate is limited, or nearly limited to its substrate diffusion rate. ... Drug interaction is a situation in which two or more separate drugs have been absorbed into the body and their effects are affected by each other, i. ... Drug interaction is a situation in which two or more separate drugs have been absorbed into the body and their effects are affected by each other, i. ...

Contents


Phase I vs. Phase II

Phase I and Phase II reactions are biotransformations of chemicals that occur during drug metabolism.


Phase I reactions usually precede Phase II, though not necessarily. During these reactions, polar bodies are either introduced or unmasked, which results in (more) polar metabolites of the original chemicals. Phase I reactions may occur by oxidation, reduction or hydrolysis reactions. If the metabolites of phase I reactions are sufficiently polar, they may be readily excreted at this point. However, many phase I products are not eliminated rapidly and undergo a subsequent reaction in which an endogenous substrate combines with the newly incorporated functional group to form a highly polar conjugate. The most fundamental reactions in chemistry are the redox processes. ... Reduction or reducing has several meanings: In mathematics, reduction is the process of manipulating a series of equations or matrices into a desired simpler format. ... Hydrolysis is a chemical process in which a molecule is split into two parts by the addition of a molecule of water. ...


Phase II reactions — usually known as conjugation reactions — are usually detoxication in nature, and involve the interactions of the polar functional groups of phase I metabolites. The major metabolites formed from most drug metabolism are detoxication products. ...


Sites

Quantitatively, the liver is the principal organ of drug metabolism, although every biological tissue has some ability to metabolize drugs. Factors responsible for the liver's contribution to drug metabolism include that it is a large organ, that it is the first organ perfused by chemicals absorbed in the gut, and that there are very high concentrations of most drug-metabolizing enzyme systems relative to other organs. If a drug is very readily and well-metabolized, it is said to show the first pass effect. The liver is one of the largest internal organs of the human body. ... Biological tissue is any substance made up of cells that perform a similar function within an organism. ... For the Physics term GUT, please refer to Grand unification theory The gastrointestinal or digestive tract, also referred to as the GI tract or the alimentary canal or the gut, is the system of organs within multicellular animals which takes in food, digests it to extract energy and nutrients, and... The first pass effect (or first pass metabolism) is a phenomenon of drug metabolism. ...


Other sites of drug metabolism include epithelial cells of the gastrointestinal tract, lungs, kidneys, and the skin. These sites are usually responsible for localized toxicity reactions. In zootomy, epithelium is a tissue composed of a layer of cells. ... The gastrointestinal tract or digestive tract, also referred to as the GI tract or the alimentary canal or the gut, is the system of organs within multicellular animals which takes in food, digests it to extract energy and nutrients, and expels the remaining waste. ... The lungs flank the heart and great vessels in the chest cavity. ... Human kidneys viewed from behind with spine removed The kidneys are bean-shaped excretory organs in vertebrates. ... Diagram of the layers of human skin In zootomy and dermatology, skin is an organ of the integumentary system composed of a layer of tissues that protect underlying muscles and organs. ...


Major enzymes and pathways

Several major enzymes and pathways are involved in drug metabolism, and can be divided into Phase I and Phase II reactions:


Phase I

Oxidation

Cytochrome P450 Oxidase (CYP2E1) Cytochrome P450 oxidase (commonly abbreviated CYP) is a generic term for a large number of related, but distinct, oxidative enzymes (EC 1. ... The Flavin-containing monooxygenase (FMO) system is used for oxidation reactions in drug metabolism. ... Alcohol Dehydrogenase Alcohol dehydrogenases are a group of dehydrogenase enzymes that occur in many organisms and facilitate the conversion between alcohols and aldehydes or ketones. ... Aldehyde Dehydrogenase Aldehyde dehydrogenases are a group of enzymes that catalyse the oxidation (dehydrogenation) of aldehydes. ... Monoamine oxidase Monoamine oxidases (singular abbreviation MAO) (EC 1. ... Glutathione Peroxidase 1 A peroxidase (eg. ...

Reduction

  • NADPH-cytochrome P450 reductase
  • Reduced (ferrous) cytochrome P450

A note is that, during reduction reactions, a chemical can enter futile cycling, in which it gains a free-radical electron, then promptly loses it to Oxygen (to form a superoxide anion). General Name, Symbol, Number oxygen, O, 8 Chemical series Nonmetals Group, Period, Block 16, 2, p Appearance colorless Atomic mass 15. ...


Hydrolysis

An esterase is an hydrolase enzyme that splits esters into a acid and an alcohol in a chemical reaction with water called hydrolysis. ... In general, the epoxide hydrolase system functions in detoxication during drug metabolism. ...

Phase II

  • Glutathione S-transferases
    • Mercapturic acid biosynthesis
  • UDP-Glucoron(os)yltransferases
  • N-Acetyltransferases
  • Amino acid N-acyl transferases
  • Sulfotransferases

The Glutathione S-transferase (GST) family of enzymes comprises a long list of cytosolic, mitochondrial, and microsomal proteins which are capable of multiple reactions with a multitude of substrates, both endogenous and xenobiotic. ...

Factors that affect drug metabolism

The duration and intensity of pharmacological action of most lipophilic drugs are determined by the rate they are metabolized to inactive products. The Cytochrome P450 monooxygenase system is the most important pathway in this regard. In general, anything that increases the rate of metabolism (e.g., enzyme induction) of a pharmacologically active metabolite will decrease the duration and intensity of the drug action. The opposite is also true (e.g., enzyme inhibition). Cytochrome P450 Oxidase (CYP2E1) Cytochrome P450 oxidase (commonly abbreviated CYP) is a generic term for a large number of related, but distinct, oxidative enzymes (EC 1. ...


Various physiological and pathological factors can also affect drug metabolism. Physiological factors that can influence drug metabolism include age, individual variation (e.g., pharmacogenetics), enterohepatic circulation, nutrition, intestinal flora, or sex differences. The terms pharmacogenomics and pharmacogenetics tend to be used interchangeably, and a precise, consensus definition of either remains elusive. ... Enterohepatic circulation, is the excretion of a drug (or a metabolite of it) through the bile to be re-absorbed in the gut and sent again to the liver along the portal vein, so the excretion-reabsortion cycle can start again. ... ‹ The template below has been proposed for deletion. ... numerous beneficial bacterial microorganisms found in the lower intestine ...


In general, drugs are metabolized more slowly in fetal, neonatal and elderly humans and animals than in adults. Fetus at eight weeks A fetus (alternatively foetus or fœtus) is an embryo in later stages of development, from the third month of pregnancy until birth in humans. ... A human infant The word Infant derives from the Latin in-fans, meaning unable to speak. ... Old age consists of ages nearing the average lifespan of human beings, and thus the end of the human life cycle. ... This article is about modern humans. ... Binomial name Aptenodytes forsteri Gray, 1844 For other uses, see Animal (disambiguation). ... The term adult describes any mature organism, but normally it refers to a human: one that is no longer a child / minor and is now either a man or a woman. ...


Genetic variation (polymorphism) accounts for some of the variability in the effect of drugs. With N-acetyltransferases (involved in Phase II reactions), individual variation creates a group of people who acetylate slowly (slow acetylators) and those who acetylate quickly, split roughly 50:50 in the population of Canada. This variation may have dramatic consequences, as the slow acetylators are more prone to dose-dependent toxicity.


Cytochrome P450 monooxygenase system enzymes can also vary across individuals, with deficiencies occurring in 1 - 30% of people, depending on their ethnic background. Cytochrome P450 Oxidase (CYP2E1) Cytochrome P450 oxidase (commonly abbreviated CYP) is a generic term for a large number of related, but distinct, oxidative enzymes (EC 1. ...


Pathological factors can also influence drug metabolism, including liver, kidney, or heart diseases. The liver is one of the largest internal organs of the human body. ... Human kidneys viewed from behind with spine removed The kidneys are bean-shaped excretory organs in vertebrates. ... The heart and lungs (from an older edition of Grays Anatomy) The heart (Latin cor) is a hollow, muscular organ in vertebrates that pumps blood through the blood vessels by repeated, rhythmic contractions, or a similar structure in annelids, mollusks, and arthropods. ...


References

  • Basic and Clinical Pharmacology (9th Edition; Katzung): 1.4. Drug Biotransformation

  Results from FactBites:
 
Reference.com/Encyclopedia/Drug metabolism (801 words)
Drug metabolism is the metabolism of drugs, their biochemical modification or degradation, usually through specialized enzymatic systems.
Factors responsible for the liver's contribution to drug metabolism include that it is a large organ, that it is the first organ perfused by chemicals absorbed in the gut, and that there are very high concentrations of most drug-metabolizing enzyme systems relative to other organs.
In general, drugs are metabolized more slowly in fetal, neonatal and elderly humans and animals than in adults.
Intramural Research Program - National Institute on Drug Abuse (1506 words)
The timecourse of drug effects are studied with simultaneous measurements of drug and metabolite plasma concentrations to better examine the relationship between the onset, peak and duration of effects and concurrent drug concentrations.
Drug testing provides a means to ensure that the mother and child receive adequate medical, social and psychological care.
For drug testing in alternate matrices to be useful, an understanding must be developed of the fundamental chemical and pharmacological principles governing the appearance and disappearance of drugs and their metabolites in these matrices.
  More results at FactBites »

 
 

COMMENTARY     


Share your thoughts, questions and commentary here
Your name
Your comments

Want to know more?
Search encyclopedia, statistics and forums:

 


Press Releases |  Feeds | Contact
The Wikipedia article included on this page is licensed under the GFDL.
Images may be subject to relevant owners' copyright.
All other elements are (c) copyright NationMaster.com 2003-5. All Rights Reserved.
Usage implies agreement with terms, 1022, m