In general, anything that increases the rate of metabolism (e.g., enzyme induction) of a pharmacologically active metabolite will decrease the duration and intensity of the drug action.
What does increased metabolism of a drug mean?
When they increase the enzyme’s metabolic function, the drug’s therapeutic effects may be decreased. When they decrease the enzyme’s metabolic function, the drug’s benefits may be compromised by intolerability. Your metabolic enzyme systems change throughout your lifetime.
Where does metabolism of drugs take place?
The liver is the principal site of drug metabolism (for review, see ). Although metabolism typically inactivates drugs, some drug metabolites are pharmacologically active—sometimes even more so than the parent compound.
Do all drugs undergo first pass metabolism?
All drugs given by the oral route undergo a degree of first pass metabolism either in the gut or the liver, with some drugs being destroyed before they reach the systemic circulation.
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 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.
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 first pass metabolism?
The first-pass metabolism or the first-pass effect or presystemic metabolism is the phenomenon which occurs whenever the drug is administered orally, enters the liver, and suffers extensive biotransformation to such an extent that the bioavailability is drastically reduced, thus showing subtherapeutic action (Chordiya …
What are some examples of drugs that have a high first pass metabolism?
Examples of drugs exhibiting first pass metabolism are aspirin and lidocaine. Some drugs, such as lidocaine, which have relatively low bioavailability are not given orally because of concern of metabolite toxicity.
How do I overcome my first pass metabolism?
Bypassing First Pass Metabolism
Two ways to bypass first pass metabolism involve giving the drug by sublingual and buccal routes. The drugs are absorbed by the oral mucosa in both methods. In sublingual administration the drug is put under the tongue where it dissolves in salivary secretions.
What factors can affect drug metabolism in the 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 gender affect drug metabolism?
Sex differences in metabolism (phase I and II) are believed to be the major cause of differential pharmacokinetics between men and women. Many CYP450 enzymes (phase I metabolism) show a sex-dependent difference in activity. Most of the phase II enzymes have a higher activity in men than in women.
How does genetic factors affect drug metabolism?
Genetic polymorphisms have been identified for many drug-metabolizing 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.