Drug metabolism (biotransformation) Drug metabolism describes the process by which the body breaks down and converts medications into active chemical substances (metabolites). Metabolism refers to the sum of all physical and chemical processes occurring in the body that maintain life. The primary site of drug metabolism is the liver. This organ plays a substantial role in metabolism, digestion and elimination of substances from the body. Enzymes in the liver are responsible for chemically changing drug components into substances known as metabolites . Metabolites bind to other substances in the body for Drug interactions Drugs can interact with other drugs, foods and beverages. Interactions can lessen or magnify the desired therapeutic effect of a drug, or may cause unwanted or unexpected side effects. There are thousands of possible drug-to-drug and drug-to-food interactions, and many medications and supplements are contraindicated under certain conditions or in patients with specific diseases and disorders. This is why it is imperative that patients always keep their physician fully informed about all drugs and dietary supplements (including herbal remedies) they are taking. Drug interactions occur in cases where one drug inhibits or produces a P-450 that acts on another drug. One familiar example is nicotine, the drug in tobacco, which is known to induce P-450s. Individuals with liver disease may also have insufficient levels of P-450 enzymes. As a result, the concentration of drugs metabolized by these enzymes is high and can increase to toxic levels. In addition, certain medications and foods, like grapefruit juice, for example, inactivate or decrease the metabolic activity of P-450s. In some cases, it may be necessary to alter drug dosage. Metabolic rates also vary significantly from person to person. A drug dosage that works quickly and effectively in one individual may not work well in another. Genetic factors as well as environmental variables, nutrition and age also influence drug metabolism. For example, infants and elderly individuals may have a reduced capacity to metabolize certain drugs, requiring an adjusted dose. Foods and beverages that interact with drugs include: ● Grapefruit juice : Grapefruit juice inhibits the metabolism of many medications, including cyclosporine, felodipine, nifedipine, nitrendipine, nisoldipine, carbamazepine, triazolam and midazolam. ● Foods and beverages with tyramines : Red wine, malted beers, smoked foods (e.g., fish and meats), dried fruits and aged cheeses may contain tyramines, and can cause a severe and dangerous elevation in blood pressure when taken with MAOI inhibitors (a class of antidepressants). ● Caffeinated beverages : The caffeine contained in coffee and colas can influence drug metabolism. ● Alcohol : Alcohol is a central nervous system depressant and should not be taken with other CNS depressants (e.g., antipsychotics, antihistamines). In addition, certain fermented beverages may contain tyramines. ● Dairy products : Milk, cream and other dairy products containing calcium can prevent the absorption of antibiotics such as tetracycline, doxycycline and ciprofloxacin when they are taken with drugs. In addition, whole milk with vitamin D can cause milk- alkali syndrome in patients taking aluminum hydroxide antacids.
excretion through the lungs, reabsorption by the intestines, or through bodily fluids including saliva, sweat, breast milk and urine. The main mode of excretion from the body is through the kidneys. A number of isoenzymes in the liver (such as cytochrome P-450) are necessary for drug metabolism. These enzymes have been labeled CYP1A2, CYP2C9, CYP2C19, CYP2D6 and CYP3A4. Each has a catabolic action on substances, breaking them down into metabolites. Through this action, they lower the concentration of medication in the bloodstream. Drugs that interact with other medicines include: ● Antibiotics : Antibiotics may reduce the efficiency of oral contraceptives. ● Metals : Medications containing metals, such as antacids with aluminum additives and iron supplements, can reduce the absorption of tetracyclines and fluoroquinolones. ● Diuretics : Diuretics can reduce serum potassium and sodium electrolyte levels when taken with digoxin and lithium, respectively. ● Monoamine oxidase inhibitors (MAOIs) : MAOI antidepressants can cause convulsions and other serious side effects when used with tricyclic antidepressants (e.g., Imipramine, Nortriptyline), selective serotonin reuptake inhibitors (SSRIs) or sympathomimetic drugs (e.g., amphetamines). ● Drugs that inhibit liver enzyme function : Drugs that slow drug metabolism include ciprofloxacin, erythromycin, fluoxetine, nefazodone, paroxetine and ritonavir. The therapeutic effect of other medications taken with these drugs may be amplified. Warfarin, a blood thinner, should be used with great caution in individuals taking these drugs. This list does not include every substance that interacts with medications. For safety, individuals must let their doctor, pharmacist and other health care professionals know when they are taking other medications, including herbal remedies and dietary supplements. If an individual experiences a serious reaction to a drug that is not mentioned on the product label, he or she should report the circumstances to the MedWatch adverse event reporting system of the United States Food and Drug Administration (FDA) and his or her doctor. Herbal supplements also produce adverse drug interactions. In 2000, the FDA issued a warning on the popular herb St. John’s wort, commonly used to treat depression. The supplement was found to inhibit the effect of indinavir, a protease inhibitor used in the treatment of HIV. It may also affect the action of cyclosporine and other protease inhibitors. Other herbs that may interact with mainstream medications include gingko biloba, ginseng and garlic, all of which may heighten the blood thinning effect of the anticoagulant warfarin. Because herbs are regulated by the FDA as dietary supplements, they do not require the same extensive clinical trials and premarket testing that drugs do before they are accepted for sale in the United States. Potential interactions and adverse effects associated with herbal supplements are a distinct danger, and individuals who experience serious side effects from dietary supplements should report them to FDA’s MedWatch program. In some cases, adverse drug reactions may be difficult to detect, closely resembling the symptoms of the disease or condition the medication was prescribed to treat. Patients
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