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词条 Drug interaction
释义

  1. Synergy and antagonism

  2. Underlying factors

  3. Analytical interference

  4. Pharmacodynamic interactions

  5. Pharmacokinetic interactions

      Absorption interactions    Changes in motility    Transport and distribution interactions    Metabolism interactions    CYP450    Enzymatic inhibition    Enzymatic induction    Excretion interactions    Renal excretion    Bile excretion  

  6. Epidemiology

  7. See also

  8. Notes

  9. References

  10. Bibliography

  11. External links

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A drug interaction is an unintended effect of using two (or more) drugs or an interaction between a drug and a food, beverage, or supplement.[1] It is defined as the change in efficacy or toxicity of one drug by prior or concomitant administration of a second drug (or other active substance).[2]

There are several possible reasons for drug interactions. One of the drugs in the combination may alter the behavior of the other drug(s) in the body, for example altering the pharmacokinetics of the drug, by altering absorption, distribution, metabolism, or excretion (ADME). Alternatively, drug interactions may result from competition between drugs for a single receptor, or when drugs target different parts of the same signaling pathway.

The risk that a drug interaction will appear increases as a function of the number of drugs administered to a patient.[3] Both the use of medications and subsequent adverse drug interactions have increased significantly between 2005-2011. 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.[4]

Synergy and antagonism

When two drugs are used together, their effects can be additive (the result is what you expect when you add together the effect of each drug taken independently), synergistic (combining the drugs leads to a larger effect than expected) or antagonistic (combining the drugs leads to a smaller effect than expected)[5]. There is sometimes confusion on whether drugs are synergistic or additive, since the individual effects of each drug may vary from patient to patient[6]. A synergistic interaction may be beneficial for patients, but may also increase the risk of overdose.

Both synergy and antagonism can occur during different phases of the interaction between a drug and an organism. For example, when synergy occurs at a cellular receptor level this is termed agonism, and the substances involved are termed agonists. On the other hand, in the case of antagonism the substances involved are known as inverse agonists. The different responses of a receptor to the action of a drug has resulted in a number of classifications, such as "partial agonist", "competitive agonist" etc. These concepts have fundamental applications in the pharmacodynamics of these interactions. 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. It is even possible that many authors would misapply any given classification.[7]

Direct interactions between drugs are also possible, and may occur when two drugs are mixed prior to intravenous injection. For example, mixing thiopentone and suxamethonium in the same syringe can lead to the precipitation of thiopentone[8].

Underlying factors

It is possible to take advantage of positive drug interactions. 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. By studying the conditions that favor the appearance of interactions it should be possible to prevent them or at least diagnose them in time. The factors or conditions that predisposes the appearance of interactions include:[7]

  • 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.[9]
  • Polypharmacy: The use of multiple drugs by a single patient, to treat one or more ailments. The more drugs a patient takes the more likely it will be that some of them will interact.[10]
  • Genetic factors: Genes synthesize enzymes that metabolize drugs. Some races have genotypic variations that could decrease or increase the activity of these enzymes. The consequence of this would, on occasions, be a greater predisposition towards drug interactions and therefore a greater predisposition for adverse effects to occur. This is seen in genotype variations in the isozymes of cytochrome P450.
  • Hepatic or renal diseases: The blood concentrations of drugs that are metabolized in the liver and/or eliminated by the kidneys may be altered if either of these organs is not functioning correctly. If this is the case an increase in blood concentration is normally seen.[10]
  • Serious diseases that could worsen if the dose of the medicine is reduced.
  • Drug dependent factors:[11]
    • Narrow therapeutic index: Where the difference between the effective dose and the toxic dose is small.[12] The drug digoxin is an example of this type of drug.
    • Steep dose-response curve: Small changes in the dosage of a drug produce large changes in the drug's concentration in the patient's blood plasma.
    • Saturable hepatic metabolism: In addition to dose effects the capacity to metabolize the drug is greatly decreased

Analytical interference

The detection of laboratory parameters is based on physicochemical reactions between the substance being measured and reagents designed for this purpose. These reactions can be altered by the presence of drugs giving rise to an overestimation or an underestimation of the real results. Levels of cholesterol and other blood lipids can be overestimated as a consequence of the presence in the blood of some psychotropic drugs. 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.

Most experts consider that these are not true interactions, so they will not be dealt with further in this discussion.[13]

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.[14] Usually the interaction is antagonistic and it almost always affects both drugs. 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. 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.

Many authors do not consider them to be interactions. An example is the database of the General Council of Official Pharmacists Colleges of Spain (Consejo General de Colegios Oficiales de Farmacéuticos de España),[15] that does not include them among the 90,000 registered interactions.

Pharmacodynamic interactions

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.

Pharmacodynamic interactions can occur on:

  1. Pharmacological receptors:&91;16&93; Receptor interactions are the most easily defined, but they are also the most common. From a pharmacodynamic perspective, two drugs can be considered to be:
    1. Homodynamic, if they act on the same receptor. They, in turn can be:
    2. Pure agonists, if they bind to the main locus of the receptor, causing a similar effect to that of the main drug.
    3. Partial agonists if, on binding to one of the receptor's secondary sites, they have the same effect as the main drug, but with a lower intensity.
    4. Antagonists, if they bind directly to the receptor's main locus but their effect is opposite to that of the main drug. These include:
    5. Competitive antagonists, if they compete with the main drug to bind with the receptor. The amount of antagonist or main drug that binds with the receptor will depend on the concentrations of each one in the plasma.
    6. Uncompetitive antagonists, when the antagonist binds to the receptor irreversibly and is not released until the receptor is saturated. In principle the quantity of antagonist and agonist that binds to the receptor will depend on their concentrations. However, the presence of the antagonist will cause the main drug to be released from the receptor regardless of the main drug's concentration, therefore all the receptors will eventually become occupied by the antagonist.
    7. Heterodynamic competitors, if they act on distinct receptors.
  2. Signal transduction mechanisms: these are molecular processes that commence after the interaction of the drug with the receptor.&91;17&93; For example, it is known that hypoglycaemia (low blood glucose) in an organism produces a release of catecholamines, which trigger compensation mechanisms thereby increasing blood glucose levels. The release of catecholamines also triggers a series of symptoms, which allows the organism to recognise what is happening and which act as a stimulant for preventative action (eating sugars). Should a patient be taking a drug such as insulin, which reduces glycaemia, and also be taking another drug such as certain beta-blockers for heart disease, then the beta-blockers will act to block the adrenaline receptors. This will block the reaction triggered by the catecholamines should a hypoglycaemic episode occur. Therefore, the body will not adopt corrective mechanisms and there will be an increased risk of a serious reaction resulting from the ingestion of both drugs at the same time.
  3. Antagonic physiological systems:&91;17&93; Imagine a drug A that acts on a certain organ. This effect will increase with increasing concentrations of physiological substance S in the organism. Now imagine a drug B that acts on another organ, which increases the amount of substance S. If both drugs are taken simultaneously it is possible that drug A could cause an adverse reaction in the organism as its effect will be indirectly increased by the action of drug B. An actual example of this interaction is found in the concomitant use of digoxin and furosemide. The former acts on cardiac fibres and its effect is increased if there are low levels of potassium (K) in blood plasma. Furosemide is a diuretic that lowers arterial tension but favours the loss of K+. This could lead to hypokalemia (low levels of potassium in the blood), which could increase the toxicity of digoxin.

Pharmacokinetic interactions

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

Absorption interactions

Changes in motility

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.

  • pH: Drugs can be present in either ionised or non-ionised form, depending on their pKa (pH at which the drug reaches equilibrium between its ionised and non-ionised form).[18] The non-ionized forms of drugs are usually easier to absorb, because they will not be repelled by the lipidic bylayer of the cell, most of them can be absorbed by passive diffusion, unless they are too big or too polarized (like glucose or vancomicyn), in which case they may have or not have specific and non specific transporters distributed on the entire intestine internal surface, that carries drugs inside the body. Obviously increasing the absorption of a drug will increase its bioavailability, so, changing the drug's state between ionized or not, can be useful or not for certain drugs.

Certain drugs require an acid stomach pH for absorption. Others require the basic pH of the intestines. Any modification in the pH could change this absorption. 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%). However, this occurs less often than an increase in pH causes an increase in absorption. Such as occurs when cimetidine is taken with didanosine. In this case a gap of two to four hours between taking the two drugs is usually sufficient to avoid the interaction.[19]

  • Drug solubility: The absorption of some drugs can be drastically reduced if they are administered together with food with a high fat content. This is the case for oral anticoagulants and avocado.
  • Formation of non-absorbable complexes:
    • Chelation: The presence of di- or trivalent cations can cause the chelation of certain drugs, making them harder to absorb. This interaction frequently occurs between drugs such as tetracycline or the fluoroquinolones and dairy products (due to the presence of Ca++).
    • Binding with proteins. Some drugs such as sucralfate binds to proteins, especially if they have a high bioavailability. For this reason its administration is contraindicated in enteral feeding.[20]
    • Finally, another possibility is that the drug is retained in the intestinal lumen forming large complexes that impede its absorption. This can occur with cholestyramine if it is associated with sulfamethoxazol, thyroxine, warfarin or digoxin.
  • Acting on the P-glycoprotein of the enterocytes: This appears to be one of the mechanisms promoted by the consumption of grapefruit juice in increasing the bioavailability of various drugs, regardless of its demonstrated inhibitory activity on first pass metabolism.[21]

Transport and distribution interactions

The main interaction mechanism is competition for plasma protein transport. 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. The organism has mechanisms to counteract these situations (by, for example, increasing plasma clearance), which means that they are not usually clinically relevant. However, these situations should be taken into account if other associated problems are present such as when the method of excretion is affected.[22]

Metabolism interactions

Many drug interactions are due to alterations in drug metabolism.[23] Further, human drug-metabolizing enzymes are typically activated through the engagement of nuclear receptors.[23] One notable system involved in metabolic drug interactions is the enzyme system comprising the cytochrome P450 oxidases.

CYP450

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.[24] 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.[25]

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. As a result of these interactions the function of the enzymes can either be stimulated (enzyme induction) or inhibited (enzyme inhibition).

Enzymatic inhibition

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. This can cause a wide range of adverse reactions.

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 A2, which actually produces the effect of the drug. If the metabolism of drug A is inhibited by drug B the concentration of A2 that is present in the blood will decrease, as will the final effect of the drug.

Enzymatic induction

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, enzymatic induction will cause a decrease in the drug's effect.

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 A2 (following the previous example) produces an increase in the drug's effect.

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.

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:[25]

  • Caffeine
  • Theophylline
  • Phenacetin
  • Clomipramine
  • Clozapine
  • Thioridazine
Drugs related to CYP1A2
Substrates Inhibitors Inductors
  • Omeprazole
  • Nicotine
  • Cimetidine
  • Ciprofloxacin
  • Phenobarbital
  • Fluvoxamine
  • Venlafaxine
  • Ticlopidine

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

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

  • Avocado
  • Brassicas (brussel sprouts, broccoli, cabbage)
Foods and their influence on drug metabolism[26],[20],[27]
Food Mechanism Drugs affected
Enzymatic inductorAcenocoumarol, warfarin
Grapefruit juiceEnzymatic inhibition
  • Calcium channel blockers: nifedipine, felodipine, nimodipine, amlodipine
  • Cyclosporine, tacrolimus
  • Terfenadine, astemizole
  • Cisapride, pimozide
  • Carbamazepine, saquinavir, midazolam, alprazolam, triazolam
{{main|Grapefruit drug interactions}}
SoyaEnzymatic inhibitionClozapine, haloperidol, olanzapine, caffeine, NSAIDs, phenytoin, zafirlukast, warfarin
GarlicIncreases antiplatelet activity
  • Anticoagulants
  • NSAIDs, acetylsalicylic acid
GinsengTo be determinedWarfarin, heparin, aspirin and NSAIDs
Ginkgo bilobaStrong inhibitor of platelet aggregation factorWarfarin, aspirin and NSAIDs
Hypericum perforatum (St John's wort)Enzymatic inductor (CYP450)Warfarin, digoxin, theophylline, cyclosporine, phenytoin and antiretrovirals
EphedraReceptor level agonistMAOI, central nervous system stimulants, alkaloids ergotamines and xanthines
Kava (Piper methysticum)UnknownLevodopa
GingerInhibits thromboxane synthetase (in vitro)Anticoagulants
ChamomileUnknownBenzodiazepines, barbiturates and opioids
HawthornUnknownBeta-adrenergic antagonists, cisapride, digoxin, quinidine

Any study of pharmacological interactions between particular medicines should also discuss the likely interactions of some medicinal plants. 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. Other drugs can modify this response and also the plants can give rise to changes in the effects of other active ingredients.

There is little data available regarding interactions involving medicinal plants for the following reasons:

  1. False sense of security regarding medicinal plants. The interaction between a medicinal plant and a drug is usually overlooked due to a belief in the "safety of medicinal plants."
  2. Variability of composition, both qualitative and quantitative. The composition of a plant-based drug is often subject to wide variations due to a number of factors such as seasonal differences in concentrations, soil type, climatic changes or the existence of different varieties or chemical races within the same plant species that have variable compositions of the active ingredient. On occasion, an interaction can be due to just one active ingredient, but this can be absent in some chemical varieties or it can be present in low concentrations, which will not cause an interaction. Counter interactions can even occur. This occurs, for instance, with ginseng, the Panax ginseng variety increases the Prothrombin time, while the Panax quinquefolius variety decreases it.&91;28&93;
  3. Absence of use in at-risk groups, such as hospitalized and polypharmacy patients, who tend to have the majority of drug interactions.
  4. Limited consumption of medicinal plants has given rise to a lack of interest in this area.&91;29&93;

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.

Excretion interactions

Renal excretion

Only the free fraction of a drug that is dissolved in the blood plasma can be removed through the kidney. 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.[30]

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. 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. 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. Therefore, these are key sites where interactions between drugs could occur.

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. 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.

  • Acetylsalicylic acid
  • Furosemide
  • Ibuprofen
  • Levodopa
  • Acetazolamide
  • Sulfadiazine
  • Ampicillin
  • Chlorothiazide
  • Paracetamol
  • Chloropropamide
  • Cromoglicic acid
  • Ethacrynic acid
  • alpha-Methyldopamine
  • Phenobarbital
  • Warfarin
  • Theophylline
  • Phenytoin
Drugs that act as weak acids or bases
Weak acids Weak bases
  • Reserpine
  • Amphetamine
  • Procaine
  • Ephedrine
  • Atropine
  • Diazepam
  • Hydralazine
  • Pindolol
  • Propranolol
  • Salbutamol
  • Alprenolol
  • Terbutaline
  • Amiloride
  • Chlorpheniramine[31]

Bile excretion

Bile excretion is different from kidney excretion as it always involves energy expenditure in active transport across the epithelium of the bile duct against a concentration gradient. This transport system can also be saturated if the plasma concentrations of the drug are high. 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. Substances with similar physicochemical properties can block the receptor, which is important in assessing interactions. 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.

Epidemiology

Among US adults older than 55, 4% are taking medication and or supplements that put them at risk of a major drug interaction.[32] Potential drug-drug interactions have increased over time[33] and are more common in the low educated elderly even after controlling for age, sex, place of residence, and comorbidity.[34]

See also

  • Deprescribing
  • Cytochrome P450
  • Classification of Pharmaco-Therapeutic Referrals
  • Polypharmacy
  • Drug interactions can be checked for free online with interaction checkers (note that not all drug interaction checkers provide the same results, and only a drug information expert, such as a pharmacist, should interpret results or provide advice on managing drug interactions)
    • Multi-Drug Interaction Checker by Medscape  
    • Drug Interactions Checker by Drugs.com [https://www.drugs.com/drug_interactions.html]

Notes

1. ^{{Cite web|url=https://aidsinfo.nih.gov/understanding-hiv-aids/fact-sheets/21/95/what-is-a-drug-interaction-|title=What is a Drug Interaction? Understanding HIV/AIDS|website=AIDSinfo|language=en-US|access-date=2019-03-22}}
2. ^{{Cite web|url=https://www.sciencedirect.com/topics/pharmacology-toxicology-and-pharmaceutical-science/drug-drug-interactions|title=ScienceDirect|website=www.sciencedirect.com|access-date=2019-03-22}}
3. ^{{cite journal | vauthors = Tannenbaum C, Sheehan NL | title = Understanding and preventing drug-drug and drug-gene interactions | journal = Expert Review of Clinical Pharmacology | volume = 7 | issue = 4 | pages = 533–44 | date = July 2014 | pmid = 24745854 | pmc = 4894065 | doi = 10.1586/17512433.2014.910111 }}
4. ^{{cite journal | vauthors = Qato DM, Wilder J, Schumm LP, Gillet V, Alexander GC | title = Changes in Prescription and Over-the-Counter Medication and Dietary Supplement Use Among Older Adults in the United States, 2005 vs 2011 | journal = JAMA Internal Medicine | volume = 176 | issue = 4 | pages = 473–82 | date = April 2016 | pmid = 26998708 | doi = 10.1001/jamainternmed.2015.8581 | pmc = 5024734 }}
5. ^{{Cite journal|last=Greco|first=W. R.|last2=Bravo|first2=G.|last3=Parsons|first3=J. C.|date=1995|title=The search for synergy: a critical review from a response surface perspective|url=https://www.ncbi.nlm.nih.gov/pubmed/7568331|journal=Pharmacological Reviews|volume=47|issue=2|pages=331–385|issn=0031-6997|pmid=7568331|via=}}
6. ^{{Cite journal|last=Palmer|first=Adam C.|last2=Sorger|first2=Peter K.|date=2017-12-14|title=Combination Cancer Therapy Can Confer Benefit via Patient-to-Patient Variability without Drug Additivity or Synergy|url=https://www.ncbi.nlm.nih.gov/pubmed/29245013|journal=Cell|volume=171|issue=7|pages=1678–1691.e13|doi=10.1016/j.cell.2017.11.009|issn=1097-4172|pmc=5741091|pmid=29245013|via=}}
7. ^1 {{cite book|url=https://books.google.com/books?id=gsb6J2sYdisC|title=Farmacología ocular|author=Baños Díez, J. E.|author2=March Pujol, M|publisher=Edicions UPC|year=2002|isbn=978-8483016473|edition=2da|pages=87|language=spanish|accessdate=23 May 2009}}
8. ^{{Cite journal|last=Khan|first=Shahab|last2=Stannard|first2=Naina|last3=Greijn|first3=Jeff|date=2011-07-12|title=Precipitation of thiopental with muscle relaxants: a potential hazard|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3147238/|journal=JRSM Short Reports|volume=2|issue=7|pages=|doi=10.1258/shorts.2011.011031|issn=2042-5333|pmc=3147238|pmid=21847440|via=}}
9. ^{{cite journal |vauthors=Merle L, Laroche ML, Dantoine T, Charmes JP | year = 2005 | title = Predicting and Preventing Adverse Drug Reactions in the Very Old | journal = Drugs & Aging | volume = 22 | issue = 5| pages = 375–392 | doi=10.2165/00002512-200522050-00003| pmid = 15903351 }}
10. ^1 García Morillo, J.S. Optimización del tratamiento de enfermos pluripatológicos en atención primaria UCAMI HHUU Virgen del Rocio. Sevilla. Spain. Available for members of SEMI at: ponencias de la II Reunión de Paciente Pluripatológico y Edad Avanzada {{webarchive|url=https://archive.is/20130414224619/http://www.fesemi.org/grupos/edad_avanzada/reuniones/ponencias_ii_pppea/view |date=2013-04-14 }}
11. ^Castells Molina, S.; Castells, S. y Hernández Pérez, M. Farmacología en enfermería Published by Elsevier Spain, 2007 {{ISBN|84-8174-993-1}}, 9788481749939 Available from [https://books.google.com/books?id=FFBjWM-PKzkC&printsec=frontcover]
12. ^The term effective dose is generally understood to mean the minimum amount of a drug that is needed to produce the required effect. The toxic dose is the minimum amount of a drug that will produce a damaging effect.
13. ^Gago Bádenas, F. Curso de Farmacología General. Tema 7.- Interacciones farmacológicas. en  
14. ^María Soledad Fernández Alfonso, Mariano Ruiz Gayo. [https://books.google.com/books?id=xhYg_jWMOUYC Fundamentos de Farmacología Básica y Clínica]. page 232. {{ISBN|84-8004-689-9}}
15. ^Panorama Actual del Medicamento, number 245, July–August 2001, pages. 583–590
16. ^{{cite web |url = http://canal-h.net/webs/sgonzalez002/Farmaco/INTERACCIONES.htm |title = Interacciones Farmacológicas |access-date = 1 January 2009 |author = S Gonzalez |language = Spanish |archive-url = https://web.archive.org/web/20090122214121/http://canal-h.net/webs/sgonzalez002/Farmaco/INTERACCIONES.htm |archive-date = 2009-01-22 |dead-url = yes |df = }}
17. ^1 Curso de Farmacología Clínica Aplicada, in El Médico Interactivo {{webarchive|url=https://web.archive.org/web/20090831065941/http://www.elmedicointeractivo.com/farmacia/temas/tema1-2/farmaa3.htm |date=2009-08-31 }}
18. ^Malgor — Valsecia, Farmacología general: Farmacocinética.Cap. 2. en {{cite web |url=http://med.unne.edu.ar/catedras/farmacologia/temas_farma/volumen1/cap2_farmacocinet.pdf |title=Archived copy |accessdate=2012-03-20 |deadurl=yes |archiveurl=https://web.archive.org/web/20120907035648/http://med.unne.edu.ar/catedras/farmacologia/temas_farma/volumen1/cap2_farmacocinet.pdf |archivedate=2012-09-07 |df= }} Revised 25 September 2008
19. ^Alicia Gutierrez Valanvia y Luis F. López-Cortés Interacciones farmacológicas entre fármacos antirretrovirales y fármacos usados para ciertos transtornos gastrointestinales. on   accessed 24 September 2008
20. ^1 Marduga Sanz, Mariano. Interacciones de los alimentos con los medicamentos. on   {{Webarchive|url=https://web.archive.org/web/20140707212321/http://www.auladelafarmacia.org/docs/AULA%20delafarmacia%20N6%20-%20Medicamentos%20y%20Servicios%20Profesionales%201.pdf |date=2014-07-07 }}
21. ^Tatro, DS. Update: Drug interaction with grapefruit juice. Druglink, 2004. 8 (5), page 35ss
22. ^Valsecia, Mabel en{{dead link|date=December 2016 |bot=InternetArchiveBot |fix-attempted=yes }}
23. ^1 {{cite news | author=Elizabeth Lipp | title=Tackling Drug-Interaction Issues Early On | url=http://www.genengnews.com/articles/chitem.aspx?aid=2509 | work=Genetic Engineering & Biotechnology News | publisher=Mary Ann Liebert, Inc. | pages=14, 16, 18, 20 | date=2008-06-15 | accessdate=2008-07-06 | quote=(subtitle) Researchers explore a number of strategies to better predict drug responses in the clinic }}
24. ^{{GoldBookRef|title=cytochrome P450|file=CT06821}} {{cite journal | vauthors = Danielson PB | title = The cytochrome P450 superfamily: biochemistry, evolution and drug metabolism in humans | journal = Current Drug Metabolism | volume = 3 | issue = 6 | pages = 561–97 | date = December 2002 | pmid = 12369887 | doi = 10.2174/1389200023337054 }}
25. ^1 Nelson D (2003). Cytochrome P450s in humans {{webarchive |url=https://web.archive.org/web/20090710050953/http://drnelson.utmem.edu/P450lect.html |date=July 10, 2009 }}. Consulted 9 May 2005.
26. ^{{cite journal | vauthors = Bailey DG, Malcolm J, Arnold O, Spence JD | title = Grapefruit juice-drug interactions | journal = British Journal of Clinical Pharmacology | volume = 46 | issue = 2 | pages = 101–10 | date = August 1998 | pmid = 9723817 | pmc = 1873672 | doi = 10.1046/j.1365-2125.1998.00764.x }}
Comment in: {{cite journal | vauthors = Mouly S, Paine MF | title = Effect of grapefruit juice on the disposition of omeprazole | journal = British Journal of Clinical Pharmacology | volume = 52 | issue = 2 | pages = 216–7 | date = August 2001 | pmid = 11488783 | pmc = 2014525 | doi = 10.1111/j.1365-2125.1978.00999.pp.x | url = http://onlinelibrary.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=0306-5251&date=2001&volume=52&issue=2&spage=216 }}{{Dead link|date=January 2019 |bot=InternetArchiveBot |fix-attempted=yes }}
27. ^{{cite journal |author=Covarrubias-Gómez, A. |title=¿Qué se auto-administra su paciente?: Interacciones farmacológicas de la medicina herbal |journal=Revista Mexicana de Anestesiología |volume=28 |issue=1 |pages=32–42 |date=January–March 2005 |url=http://www.medigraphic.com/espanol/e-htms/e-rma/e-cma2005/e-cma05-1/em-cma051f.htm |archive-url=https://archive.is/20120629232743/http://www.medigraphic.com/espanol/e-htms/e-rma/e-cma2005/e-cma05-1/em-cma051f.htm |dead-url=yes |archive-date=2012-06-29 |display-authors=etal }}
28. ^J. C. Tres Interacción entre fármacos y plantas medicinales. on {{webarchive |url=https://web.archive.org/web/20120415230850/http://www.cfnavarra.es/salud/anales/textos/vol29/n2/revis3a.html |date=April 15, 2012 }}
29. ^Zaragozá F, Ladero M, Rabasco AM et al. Plantas Medicinales (Fitoterapia Práctica). Second Edition, 2001.
30. ^Gago Bádenas, F. Curso de Farmacología General. Tema 6.- Excreción de los fármacos. en  
31. ^, Farmacología general: Farmacocinética.Cap. 2. en {{cite web |url=http://med.unne.edu.ar/catedras/farmacologia/temas_farma/volumen1/cap2_farmacocinet.pdf |title=Archived copy |accessdate=2012-03-20 |deadurl=yes |archiveurl=https://web.archive.org/web/20120907035648/http://med.unne.edu.ar/catedras/farmacologia/temas_farma/volumen1/cap2_farmacocinet.pdf |archivedate=2012-09-07 |df= }} Revised 25 September 2008
32. ^{{cite journal | vauthors = Qato DM, Alexander GC, Conti RM, Johnson M, Schumm P, Lindau ST | title = Use of prescription and over-the-counter medications and dietary supplements among older adults in the United States | journal = JAMA | volume = 300 | issue = 24 | pages = 2867–78 | date = December 2008 | pmid = 19109115 | pmc = 2702513 | doi = 10.1001/jama.2008.892 }}
33. ^{{cite journal | vauthors = Haider SI, Johnell K, Thorslund M, Fastbom J | title = Trends in polypharmacy and potential drug-drug interactions across educational groups in elderly patients in Sweden for the period 1992 - 2002 | journal = International Journal of Clinical Pharmacology and Therapeutics | volume = 45 | issue = 12 | pages = 643–53 | date = December 2007 | pmid = 18184532 | doi = 10.5414/cpp45643 }}
34. ^{{cite journal | vauthors = Haider SI, Johnell K, Weitoft GR, Thorslund M, Fastbom J | title = The influence of educational level on polypharmacy and inappropriate drug use: a register-based study of more than 600,000 older people | journal = Journal of the American Geriatrics Society | volume = 57 | issue = 1 | pages = 62–9 | date = January 2009 | pmid = 19054196 | doi = 10.1111/j.1532-5415.2008.02040.x }}

References

{{Reflist|33em}}

Bibliography

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

External links

  • Drug Interactions: What You Should Know. U.S. Food and Drug Administration, Center for Drug Evaluation and Research
  • [https://www.nlm.nih.gov/medlineplus/ On MedlinePlus there is information for non-professionals about drug interactions]
  • Medfacts Pocket Guide of Drug Interactions, Nephrology Pharmacy Associates
  • Cytochrome P450 table maintained by the Indiana University School of Medicine
  • [https://www.drugs.com/drug_interactions.html Drugs.com Drug Interaction Checker]
  • [https://web.archive.org/web/20120529064644/http://www.ehealthme.com/drug_interactions_checker EHealthme.com drug interactions checker based on 30 million reports from FDA and community]
  • 11.500 possible interactions of 5.000 substances
  • Drug-Interactions.eu. Drug interactions tool for multiple and non-drug interactions. Data from over 2500 drug labels and 5000 trials, 10000 active ingredients (drugs, metabolites, herbal and not traditional medicine products, excipients, solvents, drugs of abuse, etc.), 11000 constants, 7000 AUC ratio values, 300 enzymes.
  • {{cite web | title =What really happens when you mix medications? | website = | publisher =TED (talks) | date = | url =https://www.ted.com/talks/russ_altman_what_really_happens_when_you_mix_medications?language=en | accessdate =April 2, 2016 }}
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