This is called conjugation and the product is called a conjugate. Metabolites formed in phase 2 are unlikely to be pharmacologically active. Some drugs undergo either phase 1 or phase 2 metabolism, but most undergo phase 1 metabolism followed by phase 2 metabolism.
Do all drugs undergo metabolism?
For almost all drugs, the metabolism rate in any given pathway has an upper limit (capacity limitation). However, at therapeutic concentrations of most drugs, usually only a small fraction of the metabolizing enzyme’s sites are occupied, and the metabolism rate increases with drug concentration.
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.
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 many phases of drug metabolism are there?
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. These may occur at carbon, sulfur or nitrogen centre.
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 influences drug metabolism?
Individual drug metabolism rates are influenced by genetic factors, coexisting disorders (particularly chronic liver disorders and advanced heart failure), and drug interactions (especially those involving induction or inhibition of metabolism).
What is phase 1 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 1 metabolism occur?
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.
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 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.
Is Glucuronidation a Phase 2?
Glucuronidation is a well-characterized phase II metabolic pathway that has high capacity and provides rapid drug inactivation via the polar glucuronide metabolites produced.
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 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 route of drug absorption has the greatest bioavailability?
Generally, the order of bioavailability among different routes of administration ranked highest to lowest, is parenteral, rectal, oral, and topical, respectively.
What are the phases of biotransformation?
Biotransformation Reaction PhasesPhase IPhase IIOxidationSulfate conjugationReductionGlucuronide conjugationHydrolysisGlutathione conjugationAcetylationAmino acid conjugation