What is hepatic metabolism of drugs?

The constellation of chemical alterations to drugs or metabolites that occur in the liver,carried out by microsomal enzyme systems, which catalyze glucuronide conjugation, drug oxidation, reduction and hydrolysis.

How does the liver metabolize drugs?

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. The liver’s primary mechanism for metabolizing drugs is via a specific group of cytochrome P-450 enzymes.

What are the two categories 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. These may occur at carbon, sulfur or nitrogen centre.

What is the effect of hepatic phase II metabolism on a drug?

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 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.

How do drugs break down in the body?

Nucleoside analog drugs are not broken down by the liver but travel through the kidneys where the liver sometimes combines them with other chemicals so they can be dissolved and passed out in the urine. The cytochrome p450 system, a group of enzymes, breaks down drugs before they are metabolized by the liver.

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.

Where are drugs absorbed?

For these reasons, most drugs are absorbed primarily in the small intestine, and acids, despite their ability as un-ionized drugs to readily cross membranes, are absorbed faster in the intestine than in the stomach (for review, see [1]).

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 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 are the sites of 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. The liver’s primary mechanism for metabolizing drugs is via a specific group of cytochrome P-450 enzymes.

Which drugs would be affected by the first pass effect?

Examples of Drugs with Significant First Pass Effect or Low Bioavailability. Drug: Propranolol- ~26% Bioavailability because 75-85 % is metabolized by the liver before it can reach the circulation when taken orally. Drug: Morphine-~30% Bioavailability because 70% is metabolized via 1st pass effect if taken orally.23 мая 2016 г.

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 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.