HomeHealth articlesdrug interactionsWhat Are Drug Interactions and Its Effects on Liver?

Drug Interactions and the Liver - Different Mechanisms Involved

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The liver is a crucial organ to selectively metabolizes and processes drugs. Read this article for more details.

Written by

Dr. Gayathri. N

Medically reviewed by

Dr. Ghulam Fareed

Published At January 17, 2023
Reviewed AtJune 15, 2023

Introduction:

The major function of the liver is the excretion of drugs and toxins out of the body. This function is carried out with the help of the cytochrome P450 enzyme. Drugs can also modify how the liver functions and can cause dysfunction or failure of an organ by directly affecting the liver and causing alteration in blood flow. While some drugs can directly cause hepatotoxicity, the metabolites of these compounds can lead to drug-induced liver injury. A variety of soluble and membrane-bound enzymes process these compounds. Each drug has a specific enzyme disposal pathway of biotransformation involving one or more enzymes. Genetic variations in drug metabolism are increasingly recognized as a factor in developing a drug-induced liver injury. Although unclear, environmental factors can also alter the processing of drugs and toxins.

What Is Biotransformation?

It is a metabolic process that happens in the liver. A xenobiotic is a compound that is foreign to the liver. The liver metabolizes most drugs administered orally, which need to be metabolized and cannot be excreted. This process can involve activating inactivation drugs by making them water soluble to be excreted. Even pharmaceutical drugs are considered xenobiotic since they are foreign to the body. The main purpose of biotransformation is to convert the xenobiotics into an ineffective metabolite that will be easy to eliminate. Many other factors, such as age, sex, diseases, and genetics, influence this process.

What Is the First-Pass Effect?

The reduction in the concentration of orally administered drugs when they pass the liver is called first-pass metabolism. The fraction of a drug that escapes the liver and reaches the systemic circulation due to the first bypass effect. Some of these drugs will be lost during absorption from the intestine and more from the metabolism in the liver. The liver detects many potential toxins and tries to detoxify them. They are included in the products that the liver tries to remove.

What Is a Cytochrome P 450 Enzyme?

It is an enzyme primarily found in the liver. It can perform oxidation and reduction reactions with the help of iron to enhance the water solubility of drugs that aid in excretion. It is bound to the membranes within the cell, which also contains a pigment called haem.

What Are the Different Mechanisms Involved in the Processing of the Drug?

Drugs can be metabolized by cytochromes P450. This will make the drugs less available to the body. With aging, the capacity of the liver to metabolize through cytochrome 450 enzyme is reduced by thirty percent since the liver volume, and blood flow is decreased. Thus drugs that are metabolized in this system reach higher levels and will have a long half-life in older people. Since the newborns have partially developed hepatic microsomal enzymes, they would have difficulty metabolizing drugs.

Pharmacokinetics is described as what the body does to a drug, which also refers to the movement of the drug into, through, and out of the body. It happens through the following phases, which include

  • Bioavailability: The fraction of a drug escapes the liver and reaches the systemic circulation due to the first bypass effect. If a drug is given intravenously, it has a hundred percent bioavailability since it is all in the bloodstream. The same drug given orally will have less bioavailability since some of them will never be absorbed as it gets to stay in the gut, which can end up in the feces or get modified by the liver before it hits the vascular system.

  • Absorption: Drug absorption is determined by the drug’s physicochemical properties, formulation, and route of administration. Dosage forms (for example tablets, capsules, solutions) consisting of the drug plus other ingredients are formulated to be given by various routes (for example: oral, buccal, sublingual, rectal, parenteral, topical, and inhalational). Regardless of the route of administration, drugs must be in solution to be absorbed. Thus, solid forms (for example tablets) must be able to disintegrate and disaggregate.

  • Distribution: The entry rate of a drug into a tissue depends on the rate of blood flow to the tissue, tissue mass, and partition characteristics between blood and tissue. Distribution equilibrium (when entry and exit rates are the same) between blood and tissue is reached more rapidly in richly vascularized areas unless diffusion across cell membranes is the rate-limiting step. After equilibrium, the plasma concentration reflects drug concentrations in tissues and extracellular fluids. Metabolism and excretion occur simultaneously with distribution, making the process dynamic and complex.

  • Metabolism: The enzymes involved in metabolism are present in many tissues but generally are more concentrated in the liver. Drug metabolism rates vary among patients. Some patients metabolize a drug so rapidly that therapeutically effective blood and tissue concentrations are not reached; in others, metabolism may be so slow that usual doses have toxic effects. Individual drug metabolism rates are influenced by genetic factors, coexisting disorders (particularly long-term liver disorders and advanced heart failure), and drug interactions (especially those involving induction or inhibition of metabolism).

  • Excretion: The kidneys are the principal organs for excreting water-soluble substances. The biliary system contributes to excretion, so the drug is not reabsorbed from the gastrointestinal (GI) tract. Generally, the contribution of the intestine, saliva, sweat, breast milk, and lungs to excretion is small, except for the exhalation of volatile anesthetics.

Conclusion:

Thus, the liver is the principal site of drug metabolism. Although metabolism typically inactivates drugs, some drug metabolites are pharmacologically active, sometimes even more so than the parent compound. Thus, it is important to know about this to better understand the metabolism of drugs, which will help doctors and patients be cautious before prescribing or taking a drug.

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Dr. Ghulam Fareed
Dr. Ghulam Fareed

Medical Gastroenterology

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