In general, the metabolism of a drug decreases its therapeutic effect. The majority of drugs are metabolized to increase their water solubility to allow elimination in urine or bile. However some drugs are metabolized into active compounds first before subsequent metabolism to inactive compounds and be excreted.
What are the importance and consequences of drug metabolism?
The metabolism of a drug can have important consequences on its therapeutic effect or its toxicity. For this reason, early assessments of metabolic pathways in man help to foresee interindividual variation in drug response and elimination due to metabolism.
What are the possible effects of drug metabolism?
Drug metabolism also affects multidrug resistance in infectious diseases and in chemotherapy for cancer, and the actions of some drugs as substrates or inhibitors of enzymes involved in xenobiotic metabolism are a common reason for hazardous drug interactions.
What are the 2 major goals of drug metabolism?
The purpose of metabolism in the body is usually to change the chemical structure of the substance, to increase the ease with which it can be excreted from the body. Drugs are metabolized through various reactions including: Oxidation. Reduction.
What are the consequences of biotransformation?
Occasionally, biotransformation can produce an unusually reactive metabolite that may interact with cellular macromolecules like DNA . This can lead to very serious health effects such as cancer or birth defects.
What are the 2 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.
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.
Which organ is the primary site for drug metabolism?
Excretion involves elimination of the drug from the body, for example, in the urine or bile. 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.
Is Metabolism how the stomach breaks down medicine?
Metabolism. After a medicine has been distributed throughout the body and has done its job, the drug is broken down, or metabolized, the M in ADME. Everything that enters the bloodstream — whether swallowed, injected, inhaled or absorbed through the skin — is carried to the body’s chemical processing plant, the liver.
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.
How does genetics affect drug metabolism?
Genetic polymorphisms have been identified for many drug-metabolising enzymes, including the cytochrome P450 (CYP450) enzymes. This gives rise to distinct population phenotypes of persons who have metabolism capabilities ranging from extremely poor to extremely fast.
How can I increase my drug metabolism?
The common approaches in drug metabolism to improve PK/PD and safety of drug candidates include blocking a metabolic soft spot to lower total clearance, deuterium replacement to alter metabolism of a lead, prodrug for improved absorption and distribution, minimizing DDI and bioactivation potential, and selection of …
What is oxidation in metabolism?
Metabolic energy derives from processes of oxidation and reduction. When energy is consumed in a process, chemical energy is made available for synthesis of ATP as one atom gives up electrons (becomes oxidized) and another atom accepts electrons (becomes reduced).
Are metabolism and biotransformation the same thing?
In short, “metabolism of drugs” is a form of biotransformation which happens to drugs in a body, whereas “biotransformation” is a more general term which applies equally well to the actions of a disembodied enzyme digesting an oil slick.
What do P450 enzymes do?
Cytochromes P450 (CYPs) are a superfamily of enzymes containing heme as a cofactor that function as monooxygenases. In mammals, these proteins oxidize steroids, fatty acids, and xenobiotics, and are important for the clearance of various compounds, as well as for hormone synthesis and breakdown.
What is a Phase 1 reaction?
Phase I reactions are broadly grouped into three categories, oxidation, reduction, and hydrolysis. As most small molecule drugs are lipophilic in nature, drug metabolism converts these hydrophobic compounds into more water soluble compounds that can be excreted. Typically, oxidation is the most common phase I reaction.