Drug interaction

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Drug interaction

A drug interaction is a situation in which a substance affects the activity of a drug

Medication

A pharmaceutical drug, also referred to as medicine or medicament, can be loosely defined as any substance intended for use in the diagnosis, cure, mitigation, treatment, or prevention of disease....
, 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.

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Encyclopedia

A drug interaction is a situation in which a substance affects the activity of a drug

Medication

Probenecid

Probenecid is a uricosuric drug, primarily used in treating gout and hyperuricemia, that increases uric acid removal in the urine. One of its trade names is 'Benuryl.'...
with penicillin

Penicillin

Penicillin is a group of antibiotics derived from Penicillium fungi. They are Beta-lactam antibiotics used in the treatment of bacterial infections caused by susceptible, usually Gram-positive, organisms....
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

Carbidopa

Carbidopa is a medication given to people with Parkinson's disease in order to inhibit peripheral metabolism of levodopa....
with levodopa

Levodopa

L-DOPA is a naturally occurring amino acid found in food and made from L-Tyrosine in the human body. L-DOPA is converted into dopamine in the brain and body....
(available as Carbidopa/levodopa

Carbidopa/levodopa

The combination of carbidopa and levodopa is used to treat Parkinson's disease and Dopa-Responsive Dystonia . The generic name under the British Approved Name system is Co-careldopa....
). Levodopa is used in the management of Parkinson's disease

Parkinson's disease

Parkinson's disease is a degenerative disorder of the central nervous system that often impairs the sufferer's motor skills and speech, as well as other functions....
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

Pharmacokinetics

Pharmacokinetics is a branch of pharmacology dedicated to the determination of the fate of substances administered externally to a living organism....
of the drug, such as alterations in the Absorption, Distribution, Metabolism, and Excretion (ADME

ADME

ADME is an acronym in pharmacokinetics and pharmacology for absorption , distribution , metabolism, and excretion, and describes the disposition of a pharmaceutical Chemical compound within an organism....
) 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

Receptor antagonist

A receptor antagonist is a type of receptor ligand or drug that does not provoke a biological response itself upon binding to a Receptor , but blocks or dampens agonist-mediated responses....
and an agonist

Agonist

An agonist is a term used to describe a type of Ligand or drug that binds and alters the activity of a Receptor . The ability to alter the activity of a receptor, also known as the agonist's efficacy is a property that distinguishes it from receptor antagonist, a type of receptor ligand which also binds a receptor but which does not alter t...
for the same receptor.

Metabolic drug interactions

Many drug interactions are due to alterations in drug metabolism

Drug metabolism

Drug metabolism is the metabolism of Medication, their biochemical modification or degradation, usually through specialized Enzyme systems. This is a form of xenobiotic metabolism....
. Further, human drug-metabolizing enzymes are typically activated through engagement of nuclear receptor

Nuclear receptor

In the field of molecular biology, nuclear receptors are a class of proteins found within the interior of cells that are responsible for sensing the presence of hormone and certain other molecules....
s.

One notable system involved in metabolic drug interactions is the enzyme system comprising the cytochrome P450 oxidase

Cytochrome P450 oxidase

Cytochrome P450 is a very large and diverse superfamily of hemoproteins found in all domains of life. Cytochromes P450 use a plethora of both exogenous and endogenous compounds as substrates in enzymatic reactions....
s. 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 metabolism

Drug metabolism is the metabolism of Medication, their biochemical modification or degradation, usually through specialized Enzyme systems. This is a form of xenobiotic metabolism....
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
Drug overdose

The term drug overdose describes the ingestion or application of a drug or other substance in quantities greater than are recommended or generally practiced....
.
Bioavailability
Bioavailability

In pharmacology, bioavailability is used to describe the fraction of an administered dose of unchanged drug that reaches the systemic circulation, one of the principal pharmacokinetics properties of medication....
- drug A influences the absorption
Absorption (Pharmacokinetics)

In pharmacology , absorption is the movement of a drug into the bloodstream.Absorption involves several phases. First, the drug needs to be administered via some route of administration and in a specific dosage form such as a tablet, capsule, and so on....
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

Prodrug

A prodrug is a Pharmacology substance that is administered in an inactive form. Once administered, the prodrug is drug metabolism in vivo into an active metabolite....
, 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.

Additionally, Drug A and Drug B may affect each other's metabolism.

Epidemiology

Among US adults older then 55, 4% are taking medication and or supplements that put them at risk of a major drug interaction.

External links

. U.S. Food and Drug Administration, Center for Drug Evaluation and Research
maintained by the Indiana University School of Medicine