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.
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.
How are drugs metabolized?
Drugs can be metabolized by oxidation, reduction, hydrolysis, hydration, conjugation, condensation, or isomerization; whatever the process, the goal is to make the drug easier to excrete. The enzymes involved in metabolism are present in many tissues but generally are more concentrated in the liver.
What is drug metabolism in pharmacology?
Drug metabolism is the term used to describe the biotransformation of pharmaceutical substances in the body so that they can be eliminated more easily. The majority of metabolic processes that involve drugs occur in the liver, as the enzymes that facilitate the reactions are concentrated there.
Which of the two phases of drug metabolism produces water soluble and readily excreted metabolites?
Phase II reactions consist of those enzymatic reactions that conjugate the modified xenobiotic with another substance . The conjugated products are larger molecules than the substrate and generally polar in nature (water soluble). Thus, they can be readily excreted from the body.
What is Phase 2 drug 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.
Where does Phase 2 metabolism occur?
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 are the factors that affect drug metabolism?
Many factors affect the rate and pathway of metabolism of drugs, and the major influences can be sub-divided into internal (physiological and pathological) and external (exogenous) factors as indicated below: Internal: species, genetic (strain), sex, age, hormones, pregnancy, disease. External: diet, environment.
What are the four stages of drug metabolization?
The method by which a drug is administered, along with other factors, determines the speed of onset of effects. Drugs undergo four stages within the body: absorption, distribution, metabolism, and excretion.
What are the 3 phases of drug action?
Drug action usually occurs in three phases: Pharmaceutical phase. Pharmacokinetic phase. Pharmacodynamic phase.
What organs are involved in drug metabolism?
Most drugs must pass through the liver, which is the primary site for drug metabolism. Once in the liver, enzymes convert prodrugs to active metabolites or convert active drugs to inactive forms.
What is oxidation in drug metabolism?
In most cases, an oxygen atom is retained in the metabolite, although some reactions, such as dealkylation, result in loss of the oxygen atom in a small fragment of the original molecule. Oxidation reactions are catalysed by a diverse group of enzymes, of which the cytochrome P450 system is the most important.
What is first pass metabolism of drug?
The drug is absorbed from the GI tract and passes via the portal vein into the liver where some drugs are metabolised. Sometimes the result of first pass metabolism means that only a proportion of the drug reaches the circulation. First pass metabolism can occur in the gut and the liver.
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 factors can affect drug metabolism in an elderly?
Aging results in a number of significant changes in the human liver including reductions in liver blood flow, size, drug-metabolizing enzyme content, and pseudocapillarization. Drug metabolism is also influenced by comorbid disease, frailty, concomitant medicines, and (epi)genetics.
What is the name of the liver process in metabolism of drugs?
The liver’s primary mechanism for metabolizing drugs is via a specific group of cytochrome P-450 enzymes. The level of these cytochrome P-450 enzymes controls the rate at which many drugs are metabolized.