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Drug Interaction


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Drug Interactions

 

 

 

Drug-drug interactions occur when two or more drugs react with each other. This drug-drug interaction may cause you to experience an unexpected side effect. For example, mixing a drug you take to help you sleep (a sedative) and a drug you take for allergies (an antihistamine) can slow your reactions and make driving a car or operating machinery dangerous.

 

Drug-food/beverage interactions result from drugs reacting with foods or beverages. For example, mixing alcohol with some drugs may cause you to feel tired or slow your reactions.

Drug-condition interactions may occur when an existing medical condition makes certain drugs potentially harmful. For example, if you have high blood pressure you could experience an unwanted reaction if you take a nasal decongestant.

 

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).

 

Generally speaking, drug interactions are to be 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. Because penicillin was difficult to manufacture, it was worthwhile to find a way to reduce the amount required. Probenecid retards the excretion of penicillin, so a dose of penicillin persists longer when taken with it, and it allowed patients to take less penicillin over a course of therapy.

 

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.[1] Further, human drug-metabolizing enzymes are typically activated through engagement of nuclear receptors.[1]

 

One notable system involved in metabolic drug interactions is the enzyme system comprising the cytochrome P450 oxidases. This system may be affected by either enzyme induction or enzyme inhibition, as discussed in the examples below.

 

Enzyme induction - drug A induces the body to produce more of an enzyme which metabolises drug B. This reduces the effective concentration of drug B, which may lead to loss of effectiveness of drug B. Drug A effectiveness is not altered.

 

Enzyme inhibition - drug A inhibits the production of the enzyme metabolising drug B, thus an elevation of drug B occurs possibly leading to an overdose.

 

Bioavailability - drug A influences the absorption of drug B.

 

The examples described above may have different outcomes depending on the nature of the drugs. For example, if Drug B is a prodrug, then enzyme activation is required for the drug to reach its active form. Hence, enzyme induction by Drug A would increase the effectiveness of the drug B by increasing its metabolism to its active form. Enzyme inhibition by Drug A would decrease the effectiveness of Drug B.

 

 

This is the first article in a series of three that discuss various aspects of drug interactions. This article provides a general overview of the types of drug interactions. The second and third articles will focus on pharmacokinetic and pharmacodynamic drug interactions and drug interactions involving the cytochrome P450 metabolic enzyme pathway, respectively. To assist the pharmacist in applying this information in practice, a patient case study will be included with each article. The case study will illustrate one or more drug interactions and examples of care plans that address specific drug interaction problems.

 

Over the past two years, approximately 80 new prescription drug products have been introduced in the United States. With increasing frequency, pharmacists are being questioned by their patients whether a new prescription drug will interact with any of their routine medications. Unfortunately, each year a number of deaths occur as the direct result of patients taking a new prescription drug in combination with their existing medication regimen. A small number of drugs are withdrawn from the market annually because patients experience harmful adverse drug reactions (ADRs) or drug interactions. Although many ADRs are detected during clinical drug trials, the side effect profiles of a new drug often require more extensive use

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