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Drug Metabolism Phase 1 And 2 Pdf

drug metabolism phase 1 and 2 pdf

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Introduction to Drug Metabolism pp Cite as. The routes by which drugs may be metabolised or biotransformed are many and varied and include the chemical reactions of oxidation, reduction, hydrolysis, hydration, conjugation and condensation. It is important that these pathways are studied as the route of metabolism of a drug can determine whether it shows any pharmacological or toxicological activity.

Pathways of drug metabolism

Topics on Drug Metabolism. All organisms are constantly and unavoidably exposed to xenobiotics including both man—made and natural chemicals such as drugs, plant alkaloids, microorganism toxins, pollutants, pesticides, and other industrial chemicals. Formally, biotransformation of xenobiotics as well as endogenous compounds is subdivided into phase I and phase II reactions. On the other hand, these conjugations also play an essential role in the toxicity of many chemicals due to the metabolic formation of toxic metabolites such as reactive electrophiles. Gene polymorphism of biotransformation enzymes may often play a role in various pathophysiological processes.

Drug metabolizing enzymes DMEs play central roles in the metabolism, elimination and detoxification of xenobiotics and drugs introduced into the human body. Recently, many important advances have been made in the mechanisms that regulate the expression of these drug metabolism genes. Various nuclear receptors including the aryl hydrocarbon receptor AhR , orphan nuclear receptors, and nuclear factor-erythoroid 2 prelated factor 2 Nrf2 have been shown to be the key mediators of drug-induced changes in phase I, phase II metabolizing enzymes as well as phase III transporters involved in efflux mechanisms. The peroxisome proliferator activated receptor PPAR , which is one of the first characterized members of the nuclear hormone receptor, also dimerizes with RXR and has been shown to be activated by lipid lowering agent fibrate-type of compounds leading to transcriptional activation of the promoters on CYP4A gene. Farnesoid X receptor FXR was identified as a bile acid receptor, and its activation results in the inhibition of hepatic acid biosynthesis and increased transport of bile acids from intestinal lumen to the liver, and CYP7A is one of its target genes. The transcriptional activation by these receptors upon binding to the promoters located at the 5-flanking region of these CYP genes generally leads to the induction of their mRNA gene expression. Phase III transporters, for example, P-glycoprotein P-gp , multidrug resistance-associated proteins MRPs , and organic anion transporting polypeptide 2 OATP2 are expressed in many tissues such as the liver, intestine, kidney, and brain, and play crucial roles in drug absorption, distribution, and excretion.

Drug metabolism is the metabolic breakdown of drugs by living organisms , usually through specialized enzymatic systems. More generally, xenobiotic metabolism from the Greek xenos "stranger" and biotic "related to living beings" is the set of metabolic pathways that modify the chemical structure of xenobiotics , which are compounds foreign to an organism's normal biochemistry, such as any drug or poison. These pathways are a form of biotransformation present in all major groups of organisms and are considered to be of ancient origin. These reactions often act to detoxify poisonous compounds although in some cases the intermediates in xenobiotic metabolism can themselves cause toxic effects. The study of drug metabolism is called pharmacokinetics. The metabolism of pharmaceutical drugs is an important aspect of pharmacology and medicine.

Phase II Drug Metabolism

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Phase II Drug Metabolism

Drug metabolism

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3 Comments

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    12.06.2021 at 07:45
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  2. Felicienne D.

    12.06.2021 at 20:45
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  3. Baldwin M.

    13.06.2021 at 15:06
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    PDF | On Feb 1, , P David Josephy and others published “Phase I and Phase II” Drug Metabolism: Terminology that we Should Phase Out.

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