PT. Otsuka Indonesia

Drug Interactions : What You Should Know.

A drug interaction is a situation in which a substance affects the activity of a drug, i.e. the effects are increased or decreased, or they produce a new effect that neither produces on its own. Typically, interaction between drugs come to mind (drug-drug interaction). However, interactions may also exist between drugs & foods (drug-food interactions), as well as drugs & herbs (drug-herb interactions), drugs & micronutrients, and drugs & content of infusion solutions

Since most drug interactions have undesirable effects, generally speaking, drug interactions are avoided, due to the possibility of poor or unexpected outcomes. However, drug interactions have been deliberately used, such as co-administering probenecid with penicillin prior to mass production of penicillin.

A contemporary example of a drug interaction used as an advantage is the co-administration of carbidopa with levodopa (available as Carbidopa/levodopa). Levodopa is used in the management of Parkinson's disease and must reach the brain in an un-metabolized state to be beneficial. When given by itself, levodopa is metabolized in the peripheral tissues outside the brain, which decreases the effectiveness of the drug and increases the risk of adverse effects. However, since carbidopa inhibits the peripheral metabolism of levodopa, the co-administration of carbidopa with levodopa allows more levodopa to reach the brain un-metabolized and also reduces the risk of side effects.

Drug interactions may be the result of various processes. These processes may include alterations in the pharmacokinetics of the drug, such as alterations in the Absorption, Distribution, Metabolism, and Excretion (ADME) of a drug. Alternatively, drug interactions may be the result of the pharmacodynamic properties of the drug, e.g. the co-administration of a receptor antagonist and an agonist for the same receptor.

Metabolic drug interactions

Many drug interactions are due to alterations in drug metabolism. One notable system involved in metabolic drug interactions is the enzyme system comprising the cytochrome P450 oxidases. For example, There is a significant drug interaction between Ciprofloxacin and Methadone. Cipro may inhibit cytochrome P450 3A4 up to 65%. Since this is the primary enzyme responsible for metabolizing methadone, Cipro may elevate methadone levels significantly. This system may be affected by either enzyme induction or enzyme inhibition, as discussed in the examples below.

Maillard Reaction

Although it is not drug-drug interaction, it is important to address this issue. The Maillard reaction is a chemical reaction between an amino acid and a reducing sugar, usually requiring heat. Like caramelization, it is a form of non-enzymatic browning. The reactive carbonyl group of the sugar reacts with the nucleophilic amino group of the amino acid, and forms a variety of interesting but poorly characterized molecules responsible for a range of odors and flavors. Maillard reaction occurs when amino acids and glucose are contained in single bag. Since amino acids and glucose should be given simultaneously, a clever approach is to produce a dual-chamber bag where glucose and amino acids are separated. They are premixed prior to administration.

Further Readings:

Jakarta, 28 May 2008

Drug Interactions : What You Should Know.