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First-pass metabolism may occur in the liver (for propranolol, lidocaine, clomethiazole, and nitroglycerin) or in the gut (for benzylpenicillin and insulin). [4] The four primary systems that affect the first pass effect of a drug are the enzymes of the gastrointestinal lumen, [5] gastrointestinal wall enzymes, [6] [7] [8] bacterial enzymes [5] and hepatic enzymes.
For example, antibiotics that kill gut bacteria often reduce enterohepatic drug circulation and this requires a temporary increase of the drug's dose until the antibiotic use is discontinued and the gut repopulates with bacteria. This effect of antibiotics on enterohepatic circulation of other drugs is one of several types of drug interactions.
Drug-induced liver injury (DILI) is a cause of acute and chronic liver disease caused specifically by medications and the most common reason for a drug to be withdrawn from the market after approval. The liver plays a central role in transforming and clearing chemicals and is susceptible to the toxicity from these agents.
For example, acute-phase reactants are produced by the liver in response to injury or inflammation. The most common chronic liver disease is nonalcoholic fatty liver disease, which affects an estimated one-third of the world population. [59] Hepatitis is a common condition of inflammation of the liver.
Drug metabolism is the metabolic breakdown of drugs by living organisms, usually through specialized enzymatic systems. More generally, xenobiotic metabolism (from the Greek xenos "stranger" and biotic "related to living beings") is the set of metabolic pathways that modify the chemical structure of xenobiotics, which are compounds foreign to an organism's normal biochemistry, such as any drug ...
Hence, for drugs that are metabolized by CYP2D6 (that is, are CYP2D6 substrates), certain individuals will eliminate these drugs quickly (ultrarapid metabolizers) while others slowly (poor metabolizers). If a drug is metabolized too quickly, it may decrease the drug's efficacy while if the drug is metabolized too slowly, toxicity may result. [8]
Glucuronidation is often involved in drug metabolism of substances such as drugs, pollutants, bilirubin, androgens, estrogens, mineralocorticoids, glucocorticoids, fatty acid derivatives, retinoids, and bile acids. These linkages involve glycosidic bonds. [1]
Albumin, carries thyroid hormones and other hormones, particularly fat soluble ones, fatty acids to the liver, unconjugated bilirubin, many drugs and Ca 2+ Ceruloplasmin, carries copper; Transcortin, carries cortisol, aldosterone and progesterone; Haptoglobin, carries free hemoglobin released from erythrocytes