Drug interaction
pharmaceutical sciences, drug interactions occur when a drug's mechanism of action is affected by the concomitant administration of substances such as foods, beverages, or other drugs. A popular example of drug-food interaction is the effect of grapefruit in the metabolism of drugs .
Interactions may occur by simultaneous targeting of receptors, directly or indirectly. For example, both Zolpidem and alcohol affect GABAA receptors, and their simultaneous consumption results in the overstimulation of the receptor, which can lead to loss of consciousness. When two drugs affect each other, it receives the name of a drug-drug interaction. The risk of a drug-drug interaction (DDI) increases with the number of drugs used.[1]
A large share of elderly people regularly use five or more medications or supplements, with a significant sharte risk of side-effects from drug-drug interactions.[2] Drug interactions can be of three kinds:
It may be difficult to distinguish between synergistic or additive interactions, as individual effects of drugs may vary. Direct interactions between drugs are also possible and may occur when two drugs are mixed before suxamethonium can lead to the precipitation of thiopentone.[4]
Interactions based on pharmacodynamicsPharmacodynamic interactions are the drug-drug interactions that occur at a biochemical level and depend mainly on the biological processes of organisms. These interactions occur due to action on the same targets, for example the same receptor or signaling pathway .
 Pharmacodynamic interactions can occur on protein downstream pathways .
The interaction my also occur via signal transduction mechanisms. Interactions based on pharmacokineticsPharmacokinetics is the field of research studying the chemical and biochemical factors that directly affect dosage and the half-life of drugs in an organism, including absorption, transport, distribution, metabolism and excretion. Compounds may affect any of those process, ultimately interfering with the flux of drugs in the human body, increasing or reducing drug availability. Based on absorptionDrugs that change intestinal motility may impact the level of other drugs taken. For example, intestinal motility, which may cause drugs to go through the digestive system too fast, reducing absorption. [citation needed ]
The pharmacological modification of pKa, and neutral compounds are usually better absorbed by membranes.[7] Medication like antacids can increase pH and inhibit the absorption of other drugs such as zalcitabine, tipranavir and amprenavir. The opposite is more common, with, for example, the antacid cimetidine stimulating the absorption of didanosine. Some resources describe that a gap of two to four hours between taking the two drugs is needed to avoid the interaction.[8]
Factors such as food with contraindicated in enteral feeding.[9]
Some drugs also alter absorption by acting on the P-glycoprotein of the enterocytes. This appears to be one of the mechanisms by which grapefruit juice increases the bioavailability of various drugs beyond its inhibitory activity on first pass metabolism.[10] Based on transport and distributionDrugs also may affect each other by competing for transport proteins in plasma clearance), and thus they are not usually clinically relevant. They may become relevant if other problems are present, such as issues with drug excretion.[11]
Based on metabolism Many drug interactions are due to alterations in cytochrome P450 oxidases .
CYP450haemoproteins (hemoproteins) that are characterized by their enzymatic activity and their role in the metabolism of a large number of drugs.[13] Of the various families that are present in humans, the most interesting in this respect are the 1, 2 and 3, and the most important enzymes are CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP2E1 and CYP3A4.[14]
The majority of the enzymes are also involved in the metabolism of enzyme inhibition ).
Through enzymatic inhibition and inductionIf a drug is metabolized by a CYP450 enzyme and drug B blocks the activity of these enzymes, it can lead to pharmacokinetic alterations. A. This alteration results in drug A remaining in the bloodstream for an extended duration, and eventually increase in concentration.[citation needed] In some instances, the inhibition may reduce the therapeutic effect, if instead the metabolites of the drug is responsible for the effect.[citation needed] Compounds that increase the efficiency of the enzymes, on the other hand, may have the opposite effect and increase the rate of metabolism. Examples of metabolism-based interactionsAn example of this is shown in the following table for the CYP1A2 enzyme, showing the substrates (drugs metabolized by this enzyme) and some inductors and inhibitors of its activity:[14]
Some foods also act as inductors or inhibitors of enzymatic activity. The following table shows the most common:
Based on excretionRenal and biliary excretionDrugs tightly bound to proteins (i.e. not in the renal excretion.[17]
Filtration depends on a number of factors including the pH of the urine. Drug interactions may affect those points. [citation needed]
With herbal medicinesHerb-drug interactions are drug interactions that occur between ExamplesExamples of herb-drug interactions include, but are not limited to:
MechanismsThe mechanisms underlying most herb-drug interactions are not fully understood.[25] Interactions between herbal medicines and anticancer drugs typically involve enzymes that metabolize cytochrome P450.[23] For example, St. John's Wort has been shown to induce CYP3A4 and P-glycoprotein in vitro and in vivo.[23] Underlying factorsThe factors or conditions that predispose the appearance of interactions include factors [26]Old age: factors relating to how human physiology changes with age may affect the interaction of drugs. For example, liver metabolism, kidney function, nerve transmission, or the functioning of bone marrow all decrease with age. In addition, in old age, there is a sensory decrease that increases the chances of errors being made in the administration of drugs.[27] The elderly are also more vulnerable to polypharmacy, and the more drugs a patient takes, higher is the chance of an interaction.[28] Genetic factors may also affect the enzymes and receptors, thus altering the possibilities of interactions. [citation needed] Parients with renal diseases already may have difficulties metabolizing and excreding drugs, what may exacerbate the effect of interactions.[28]
Some drugs present an intrinsic increased risk for a harmful interaction, including drugs with a narrow therapeutic index, where the difference between the effective dose and the toxic dose is small.[n. 1] The drug digoxin is an example of this type of drug.[29] Risks are also increased when the drug presents a steep dose-response curve, and small changes in the dosage produce large changes in the drug's concentration in the blood plasma.[29]
EpidemiologyAs of 2008, among adults in the elderly even after controlling for age, sex, place of residence, and comorbidity.[32]
See alsoNotes
References
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