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Drug interaction


Udocheals.orgDrug interactions
7.20.2017 | Logan Miers
Drug interactions
Drug interaction

They are usually included in the category of foods as they are usually taken as a tea or food supplement. However, medicinal plants are increasingly being taken in a manner more often associated with conventional medicines: pills, tablets, capsules, etc.

Many authors do not consider them to be interactions in the strictest sense of the word. An example is the database of the General Council of Official Pharmacists Colleges of Spain (Consejo General de Colegios Oficiales de Farmacéuticos de España), that does not include them among the 90,000 registered interactions.

Usually the interaction is antagonistic and it almost always affects both drugs. The interaction of some drugs with the transport medium can also be included here. This means that certain drugs cannot be administered in plastic bottles because they bind with the bottle's walls, reducing the drug's concentration in solution. These chemical reactions are also known as pharmacological incompatibilities. The reactions occur when two or more drugs are mixed outside the body of the organism for the purpose of joint administration. Examples of these types of interactions include the mixing of penicillins and aminoglycosides in the same serum bottle, which causes the formation of an insoluble precipitate, or the mixing of ciprofloxacin with furosemide.

As in the previous case it is possible to find paradoxical situations where an active metabolite causes the drug's effect. In this case the increase in active metabolite A 2 (following the previous example) produces an increase in the drug's effect.

By studying the conditions that favour the appearance of interactions it should be possible to prevent them or at least diagnose them in time. However, the negative interactions are usually of more interest because of their pathological significance and also because they are often unexpected and may even go undiagnosed. The factors or conditions that predispose or favor the appearance of interactions include:. It is possible to take advantage of positive drug interactions.

Certain drugs require an acid stomach pH for absorption. Others require the basic pH of the intestines. In the case of the antacids, an increase in pH can inhibit the absorption of other drugs such as zalcitabine (absorption can be decreased by 25%), tipranavir (25%) and amprenavir (up to 35%). Any modification in the pH could change this absorption. In this case a gap of two to four hours between taking the two drugs is usually sufficient to avoid the interaction. However, this occurs less often than an increase in pH causes an increase in absorption. Such as occurs when cimetidine is taken with didanosine.

The following table shows the most common:. Some foods also act as inductors or inhibitors of enzymatic activity.

These changes are basically modifications in the concentration of the drugs. Modifications in the effect of a drug are caused by differences in the absorption, transport, distribution, metabolization or excretion of one or both of the drugs compared with the expected behaviour of each drug when taken individually. In this respect two drugs can be homergic if they have the same effect in the organism and heterergic if their effects are different.

One notable system involved in metabolic drug interactions is the enzyme system comprising the cytochrome P450 oxidases. Many drug interactions are due to alterations in drug metabolism. Further, human drug-metabolizing enzymes are typically activated through the engagement of nuclear receptors.

Over 100 drugs depend on its metabolism for their activity and many others act on the enzyme as inductors or inhibitors. Enzyme CYP3A4 is the enzyme that the greatest number of drugs use as a substrate.

It is possible that this can occasionally lead to a paradoxical situation, where the enzymatic inhibition causes a decrease in the drug's effect: if the metabolism of drug A gives rise to product A 2, which actually produces the effect of the drug. If the metabolism of drug A is inhibited by drug B the concentration of A 2 that is present in the blood will decrease, as will the final effect of the drug.

Among US adults older than 55, 4% are taking medication and or supplements that put them at risk of a major drug interaction. Potential drug-drug interactions have increased over time and are more common in the low educated elderly even after controlling for age, sex, place of residence, and comorbidity.

In other situations, the interaction does not involve any effect on the drug. foods or alcohol ). It is possible that an interaction will occur between a drug and another substance present in the organism (i.e. In certain cases, the presence of a drug in an individual's blood may affect certain types of laboratory analysis ( analytical interference ). Or in certain specific situations a drug may even react with itself, such as occurs with dehydration.

Pharmacodynamic interactions can occur on:

When the interaction causes an increase in the effects of one or both of the drugs the interaction is called a synergistic effect. These authors use the term "additive effect" for additive synergy and they reserve use of the term "synergistic effect" for enhanced synergy. When the final effect is much greater than the sum of the two effects this is called enhanced synergy. An "additive synergy" occurs when the final effect is equal to the sum of the effects of the two drugs (Although some authors argue that this is not true synergy). The opposite effect to synergy is termed antagonism. Two drugs are antagonistic when their interaction causes a decrease in the effects of one or both of the drugs. This concept is recognized by the majority of authors, although other authors only refer to synergy when there is an enhanced effect.

The risk that a pharmacological interaction will appear increases as a function of the number of drugs administered to a patient at the same time. The pharmaceutical interactions that are of special interest to the practice of medicine are primarily those that have negative effects for an organism. Both the use of medications and subsequent adverse drug interactions have increased significantly between. Over a third (36%) of older adults in the U.S. regularly use 5 or more medications or supplements and 15% are potentially at risk for a major drug-drug interaction.

On the other hand, if the action of a drug is reduced it may cease to have any therapeutic use because of under dosage. Notwithstanding the above, on occasion these interactions may be sought in order to obtain an improved therapeutic effect. Examples of this include the use of codeine with paracetamol to increase its analgesic effect. Or the combination of clavulanic acid with amoxicillin in order to overcome bacterial resistance to the antibiotic. It should also be remembered that there are interactions that, from a theoretical standpoint, may occur but in clinical practice have no important repercussions. It is therefore easy to see the importance of these pharmacological interactions in the practice of medicine. The interaction of the two drugs may also increase the risk that side effects will occur. If a patient is taking two drugs and one of them increases the effect of the other it is possible that an overdose may occur.

It can often occur that a patient is taking two drugs that are enzymatic inductors, one inductor and the other inhibitor or both inhibitors, which greatly complicates the control of an individual's medication and the avoidance of possible adverse reactions.

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. Drug interactions may be the result of various processes.

An example of this is shown in the following table for the CYP1A2 enzyme, which is the most common enzyme found in the human liver. The table shows the substrates (drugs metabolized by this enzyme) and the inductors and inhibitors of its activity:.

Levels of cholesterol and other blood lipids can be overestimated as a consequence of the presence in the blood of some psychotropic drugs. The detection of laboratory parameters is based on physicochemical reactions between the substance being measured and reagents designed for this purpose. Most experts consider that these are not true interactions, so they will not be dealt with further in this discussion. These overestimates should not be confused with the action of other drugs that actually increase blood cholesterol levels due to an interaction with its metabolism. These reactions can be altered by the presence of drugs giving rise to an over estimation or an underestimation of the real results.

Some drugs, such as the prokinetic agents increase the speed with which a substance passes through the intestines. If a drug is present in the digestive tract's absorption zone for less time its blood concentration will decrease. The opposite will occur with drugs that decrease intestinal motility.

As a result, enzymatic induction will cause a decrease in the drug's effect. If drug A is metabolized by a cytochrome P450 enzyme and drug B induces or increases the enzyme's activity, then blood plasma concentrations of drug A will quickly fall as its inactivation will take place more rapidly.

As a result of these interactions the function of the enzymes can either be stimulated ( enzyme induction ) or inhibited ( enzyme inhibition ). The majority of the enzymes are also involved in the metabolism of endogenous substances, such as steroids or sex hormones, which is also important should there be interference with these substances. Of the various families that are present in human beings 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. Cytochrome P450 is a very large family of haemoproteins (hemoproteins) that are characterized by their enzymatic activity and their role in the metabolism of a large number of drugs.

On the other hand, in the case of antagonism the substances involved are known as inverse agonists. The proliferation of existing classifications at this level, along with the fact that the exact reaction mechanisms for many drugs are not well understood means that it is almost impossible to offer a clear classification for these concepts. For example, when the synergy occurs at a cellular receptor level this is termed agonism, and the substances involved are termed agonists. It is even likely that many authors would misapply any given classification. These concepts have fundamental applications in the pharmacodynamics of these interactions. Both synergy and antagonism can both occur during different phases of the interaction of a drug with an organism, with each effect having a different name. The different responses of a receptor to the action of a drug has resulted in a number of classifications, which use terms such as "partial agonist", "competitive agonist" etc.

The change in an organism's response on administration of a drug is an important factor in pharmacodynamic interactions. These changes are extraordinarily difficult to classify given the wide variety of modes of action that exist and the fact that many drugs can cause their effect through a number of different mechanisms. This wide diversity also means that, in all but the most obvious cases, it is important to investigate and understand these mechanisms. The well-founded suspicion exists that there are more unknown interactions than known ones.

These situations will all be discussed under the same heading due to their conceptual similarity. It is also possible for interactions to occur outside an organism before administration of the drugs has taken place. This can occur when two drugs are mixed, for example, in a saline solution prior to intravenous injection. Some classic examples of this type of interaction include that thiopentone and suxamethonium should not be placed in the same syringe and same is true for benzylpenicillin and heparin.

Other drugs can modify this response and also the plants can give rise to changes in the effects of other active ingredients. The effects caused by medicinal plants should be considered in the same way as those of medicines as their interaction with the organism gives rise to a pharmacological response. Any study of pharmacological interactions between particular medicines should also discuss the likely interactions of some medicinal plants. There is little data available regarding interactions involving medicinal plants for the following reasons:.

The excretion of drugs from the kidney's nephrons has the same properties as that of any other organic solute: passive filtration, reabsorption and active secretion. Filtration depends on a number of factors including the pH of the urine, it having been shown that the drugs that act as weak bases are increasingly excreted as the pH of the urine becomes more acidic, and the inverse is true for weak acids. Therefore, drugs that are tightly bound to proteins are not available for renal excretion, as long as they are not metabolized when they may be eliminated as metabolites. In the latter phase the secretion of drugs is an active process that is subject to conditions relating to the saturability of the transported molecule and competition between substrates. Only the free fraction of a drug that is dissolved in the blood plasma can be removed through the kidney. Therefore, these are key sites where interactions between drugs could occur. This mechanism is of great use when treating intoxications (by making the urine more acidic or more alkali) and it is also used by some drugs and herbal products to produce their interactive effect. Creatinine clearance is used as a measure of kidney functioning but it is only useful in cases where the drug is excreted in an unaltered form in the urine.

This can cause a wide range of adverse reactions. If drug A is metabolized by a cytochrome P450 enzyme and drug B inhibits or decreases the enzyme's activity, then drug A will remain with high levels in the plasma for longer as its inactivation is slower. As a result, enzymatic inhibition will cause an increase in the drug's effect.

Interacciones de fármacos y sus implicancias clínicas. 1997. Chap. (J. Flórez y col. In: Farmacología Humana. Eds). MA Cos. Masson SA, Barcelona. 165–176. 10, pp.

These interactions may occur out of accidental misuse or due to lack of knowledge about the active ingredients involved in the relevant substances. This action can be synergistic (when the drug's effect is increased) or antagonistic (when the drug's effect is decreased) or a new effect can be produced that neither produces on its own. A drug interaction is a situation in which a substance (usually another drug) affects the activity of a drug when both are administered together. Typically, interactions between drugs come to mind (drug-drug interaction). People taking antidepressant drugs such as monoamine oxidase inhibitors should not take food containing tyramine as hypertensive crisis may occur (an example of a drug-food interaction). However, interactions may also exist between drugs and foods (drug-food interactions), as well as drugs and medicinal plants or herbs ( drug-plant interactions ).

In these cases the drug that arrives first binds with the plasma protein, leaving the other drug dissolved in the plasma, which modifies its concentration. However, these situations should be taken into account if there other associated problems are present such as when the method of excretion is affected. The organism has mechanisms to counteract these situations (by, for example, increasing plasma clearance ), which means that they are not usually clinically relevant. The main interaction mechanism is competition for plasma protein transport.

A drug excreted in the bile duct can occasionally be reabsorbed by the intestines (in the entero-hepatic circuit), which can also lead to interactions with other drugs. Substances with similar physicochemical properties can block the receptor, which is important in assessing interactions. Bile excretion of drugs mainly takes place where their molecular weight is greater than 300 and they contain both polar and lipophilic groups. The glucuronidation of the drug in the kidney also facilitates bile excretion. This transport system can also be saturated if the plasma concentrations of the drug are high. Bile excretion is different from kidney excretion as it is always involves energy expenditure in active transport across the epithelium of the bile duct against a concentration gradient.

Drug interactions