Although Phase I drug metabolism occurs in most tissues, the primary and first pass site of metabolism occurs during hepatic circulation. Additional metabolism occurs in gastrointestinal epithelial, renal, skin, and lung tissues.
Where does Phase 1 and 2 metabolism occur?
The liver is the primary site for metabolism. Liver contains the necessary enzymes for metabolism of drugs and other xenobiotics. These enzymes induce two metabolism pathways: Phase I (functionalization reactions) and Phase II (biosynthetic reactions) metabolism.
What is first phase metabolism?
Phase 1 metabolism involves chemical reactions such as oxidation (most common), reduction and hydrolysis. There are three possible results of phase 1 metabolism. The drug becomes completely inactive. … One or more of the metabolites are pharmacologically active, but less so than the original drug.
Where does phase 2 drug metabolism take place?
Conjugation. Glucuronidation, the most common phase II reaction, is the only one that occurs in the liver microsomal enzyme system. Glucuronides are secreted in bile and eliminated in urine. Thus, conjugation makes most drugs more soluble and easily excreted by the kidneys.
What is the difference between Phase 1 and Phase 2 metabolism?
Phase I reactions of drug metabolism involve oxidation, reduction, or hydrolysis of the parent drug, resulting in its conversion to a more polar molecule. Phase II reactions involve conjugation by coupling the drug or its metabolites to another molecule, such as glucuronidation, acylation, sulfate, or glicine.
Is first pass metabolism the same as Phase 1?
Phase 1 reactions are often oxidations or hydrolysis reactions, although reductions also occur. In terms of first-pass metabolism in the liver – hydrolysis of pharmacologically inactive esters (prodrugs) to active drugs are important phase 1 reactions.
What are the two routes by which drugs can be eliminated into the system?
Renal excretion is the most common route of drug elimination. However, many drugs are excreted into bile via the liver and some volatile substances (primarily gaseous anesthetics) can be excreted via the lungs.
What are the two phases of drug metabolism?
Drug metabolism reactions comprise of two phases: Phase I (functionalization) reactions such as oxidation, hydrolysis; and Phase II (conjugation) reactions such as glucuronidation, sulphate conjugation. Oxidation reactions are the most common and vital.
Why does first pass metabolism occur?
The drug is absorbed from the GI tract and passes via the portal vein into the liver where some drugs are metabolised. … For example, first pass metabolism occurs in the gut for benzylpenicillin and insulin and in the liver for propranolol, lignocane, chloromethiasole and GTN.
What is Glucuronidation metabolism?
Glucuronidation involves the metabolism of parent compound by UDP-glucuronosyltransferases (UGTs) into hydrophilic and negatively charged glucuronides that cannot exit the cell without the aid of efflux transporters.22 мая 2017 г.
What is involved in Phases I and II of biotransformation?
The first phase involves oxidations, reductions or hydrolyses or a combination of any of these three, and for convenience these may be termed “phase I reactions”; the second phase (“phase II reactions”) consists of synthesis, mainly conjugations such as glucuronide, ethereal sulphate, thiocyanate, and hippuric acid …
What happens if a drug is not metabolized?
The substances that result from metabolism (metabolites) may be inactive, or they may be similar to or different from the original drug in therapeutic activity or toxicity. Some drugs, called prodrugs, are administered in an inactive form, which is metabolized into an active form.
What causes slow drug metabolism?
Underlying health conditions can also influence your drug metabolic rate. Some concerning ones are chronic liver disorders, kidney dysfunction, or advanced heart failure. Drug and Food Interactions. CYP450 enzymes can be impacted by the foods you eat and other drugs you take.
What is second pass metabolism?
GC -> Liver. Second-pass metabolism is where the drug comes back to the liver from the circulation.
What is the enzyme responsible for the first phase?
In phase I, enzymes such as cytochrome P450 oxidases introduce reactive or polar groups into xenobiotics. These modified compounds are then conjugated to polar compounds in phase II reactions. These reactions are catalysed by transferase enzymes such as glutathione S-transferases.
What is oxidation in metabolism?
Listen to pronunciation. (OK-sih-DAY-tiv meh-TA-buh-lih-zum) A chemical process in which oxygen is used to make energy from carbohydrates (sugars). Also called aerobic metabolism, aerobic respiration, and cell respiration.