Drug interaction
Encyclopedia
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). These may occur out of accidental misuse or due to lack of knowledge about the active ingredients involved in the relevant substances.
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.
. Further, human drug-metabolizing enzymes are typically activated through engagement of nuclear receptor
s.
One notable system involved in metabolic drug interactions is the enzyme system comprising the cytochrome P450 oxidase
s. This system may be affected by either enzyme induction or enzyme inhibition, as discussed in the examples below.
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.
Additionally, Drug A and Drug B may affect each other's metabolism.
Medication
A pharmaceutical drug, also referred to as medicine, medication or medicament, can be loosely defined as any chemical substance intended for use in the medical diagnosis, cure, treatment, or prevention of disease.- Classification :...
, 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). These may occur out of accidental misuse or due to lack of knowledge about the active ingredients involved in the relevant substances.
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
Probenecid
Probenecid is a uricosuric drug that increases uric acid excretion in the urine. It is primarily used in treating gout and hyperuricemia.Probenecid was developed as an alternative to caronamide...
with penicillin
Penicillin
Penicillin is a group of antibiotics derived from Penicillium fungi. They include penicillin G, procaine penicillin, benzathine penicillin, and penicillin V....
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 drug given to people with Parkinson's disease in order to inhibit peripheral metabolism of levodopa.- Pharmacology :...
with levodopa
Levodopa
L-DOPA is a chemical that is made and used as part of the normal biology of some animals and plants. Some animals including humans make it via biosynthesis from the amino acid L-tyrosine. L-DOPA is the precursor to the neurotransmitters dopamine, norepinephrine , and epinephrine collectively...
(available as Carbidopa/levodopa
Carbidopa/levodopa
Carbidopa/levodopa is the combination of carbidopa and levodopa and is used to treat Parkinson's disease and dopamine-responsive dystonia . It is sold under several brand names, including Sinemet, Parcopa, and Atamet...
). 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...
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, sometimes abbreviated as PK, 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 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 chemical that binds to a receptor of a cell and triggers a response by that cell. Agonists often mimic the action of a naturally occurring substance...
for the same receptor.
Metabolic drug interactions
Many drug interactions are due to alterations in drug metabolismDrug metabolism
Drug metabolism is the biochemical modification of pharmaceutical substances by living organisms, usually through specialized enzymatic systems. This is a form of xenobiotic metabolism. Drug metabolism often converts lipophilic chemical compounds into more readily excreted polar products...
. 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 cells that are responsible for sensing steroid and thyroid hormones 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
The cytochrome P450 superfamily is a large and diverse group of enzymes. The function of most CYP enzymes is to catalyze the oxidation of organic substances. The substrates of CYP enzymes include metabolic intermediates such as lipids and steroidal hormones, as well as xenobiotic substances...
s. This system may be affected by either enzyme induction or enzyme inhibition, as discussed in the examples below.
- Enzyme inductionEnzyme induction and inhibitionEnzyme induction is a process in which a molecule induces the expression of an enzyme.Enzyme inhibition can refer to* the inhibition of the expression of the enzyme by another molecule...
- drug A induces the body to produce more of an enzyme which metabolisesDrug metabolismDrug metabolism is the biochemical modification of pharmaceutical substances by living organisms, usually through specialized enzymatic systems. This is a form of xenobiotic metabolism. Drug metabolism often converts lipophilic chemical compounds into more readily excreted polar products...
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 inhibitionEnzyme induction and inhibitionEnzyme induction is a process in which a molecule induces the expression of an enzyme.Enzyme inhibition can refer to* the inhibition of the expression of the enzyme by another molecule...
- drug A inhibits the production of the enzyme metabolising drug B, thus an elevation of drug B occurs possibly leading to an overdoseDrug overdoseThe term drug overdose describes the ingestion or application of a drug or other substance in quantities greater than are recommended or generally practiced...
. - BioavailabilityBioavailabilityIn pharmacology, bioavailability is a subcategory of absorption and is used to describe the fraction of an administered dose of unchanged drug that reaches the systemic circulation, one of the principal pharmacokinetic properties of drugs. By definition, when a medication is administered...
- drug A influences the absorptionAbsorption (Pharmacokinetics)In pharmacology , absorption is the movement of a drug into the bloodstream.Absorption involves several phases...
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 pharmacological substance administered in an inactive form. Once administered, the prodrug is metabolised in vivo into an active metabolite, a process termed bioactivation. The rationale behind the use of a prodrug is generally for absorption, distribution, metabolism, and...
, 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 than 55, 4% are taking medication and or supplements that put them at risk of a major drug interaction.External links
- Drug Interactions: What You Should Know. U.S. Food and Drug Administration, Center for Drug Evaluation and Research
- Medfacts Pocket guide for Drug Interaction Published by Nephrology pharmacy associates NPA Second Edition
- Cytochome P450 table maintained by the Indiana University School of Medicine
- Free Drug Interaction Checker