Drug interaction

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Grapefruit juice can act as an enzyme inhibitor, affecting the metabolism of drugs. Citrus paradisi (Grapefruit, pink) white bg.jpg
Grapefruit juice can act as an enzyme inhibitor, affecting the metabolism of drugs.

In 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.

Contents

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 intravenous injection. For example, mixing thiopentone and suxamethonium can lead to the precipitation of thiopentone. [4]

Interactions based on pharmacodynamics

Pharmacodynamic 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.

Effects of the competitive inhibition of an agonist by increases in the concentration of an antagonist. A drug's potency can be affected (the response curve shifted to the right) by the presence of an antagonistic interaction. Agonist Antagonist.svg
Effects of the competitive inhibition of an agonist by increases in the concentration of an antagonist. A drug's potency can be affected (the response curve shifted to the right) by the presence of an antagonistic interaction.

Pharmacodynamic interactions can occur on protein receptors. [5] Two drugs can be considered to be Homodynamic, if they act on the same receptor. Homodynamic effects include drugs that act as (1) pure agonists, if they bind to the main locus of the receptor, causing a similar effect to that of the main drug, (2) partial agonists if, on binding to a secondary site, they have the same effect as the main drug, but with a lower intensity and (3) antagonists, if they bind directly to the receptor's main locus but their effect is opposite to that of the main drug. These may be competitive antagonists, if they compete with the main drug to bind with the receptor. or uncompetitive antagonists, when the antagonist binds to the receptor irreversibly. The drugs can be considered Heterodynamic competitors, if they act on distinct receptor with similar downstream pathways.

The interaction my also occur via signal transduction mechanisms. [6] For example, low blood glucose leads to a release of catecholamines, triggering symptoms that hint the organism to take action, including the eating sugar. If a patient is on insulin, which reduces blood sugar, and also beta-blockers, the body is less able to cope with an insulin overdose.

Interactions based on pharmacokinetics

Pharmacokinetics 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 absorption

Drugs that change intestinal motility may impact the level of other drugs taken. For example, prokinetic agents increase the intestinal motility, which may cause drugs to go through the digestive system too fast, reducing absorption. [ citation needed ]

The pharmacological modification of pH can also affect other compounds. Drugs can be present in ionized or non-ionized forms depending on 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 high-fat content may also alter the solubility of drugs and impact its absorption. This is the case for oral anticoagulants and avocado.[ citation needed ] The formation of non-absorbable complexes may occur also via chelation, when cations can make certain drugs harder to absorb, for example between tetracycline or the fluoroquinolones and dairy products, due to the presence of calcium ions.[ citation needed ] . Other drugps 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. [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 distribution

Drugs also may affect each other by competing for transport proteins in plasma, such as albumin. In these cases the drug that arrives first binds with the plasma protein, leaving the other drug dissolved in the plasma, modifying its expected concentration. The organism has mechanisms to counteract these situations (by, for example, increasing 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

Diagram of cytochrome P450 isoenzyme 2C9 with the haem group in the centre of the enzyme. CYP2C9 1OG2.png
Diagram of cytochrome P450 isoenzyme 2C9 with the haem group in the centre of the enzyme.

Many drug interactions are due to alterations in drug metabolism. [12] Further, human drug-metabolizing enzymes are typically activated through the engagement of nuclear receptors. [12] 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. [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 endogenous substances, such as steroids or sex hormones, which is also important should there be interference with these substances. The function of the enzymes can either be stimulated (enzyme induction) or inhibited (enzyme inhibition).

Through enzymatic inhibition and induction

If 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 interactions

An 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]

Drugs related to CYP1A2
SubstratesInhibitorsInductors

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

Foods and their influence on drug metabolism [15] [9] [16]
FoodMechanismDrugs affected
Enzymatic inductor Acenocoumarol, warfarin
Grapefruit juiceEnzymatic inhibition
Soya Enzymatic inhibition Clozapine, haloperidol, olanzapine, caffeine, NSAIDs, phenytoin, zafirlukast, warfarin
Garlic Increases antiplatelet activity
Ginseng To be determined Warfarin, heparin, aspirin and NSAIDs
Ginkgo biloba Strong inhibitor of platelet aggregation factor Warfarin, aspirin and NSAIDs
Hypericum perforatum (St John's wort)Enzymatic inductor (CYP450)Warfarin, digoxin, theophylline, cyclosporine, phenytoin and antiretrovirals
Ephedra Receptor level agonist MAOI, central nervous system stimulants, alkaloids ergotamines and xanthines
Kava (Piper methysticum)Unknown Levodopa
Ginger Inhibits thromboxane synthetase (in vitro)Anticoagulants
ChamomileUnknown Benzodiazepines, barbiturates and opioids
Hawthorn UnknownBeta-adrenergic antagonists, cisapride, digoxin, quinidine

Based on excretion

Renal and biliary excretion

Drugs tightly bound to proteins (i.e. not in the free fraction) are not available for 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 medicines

Herb-drug interactions are drug interactions that occur between herbal medicines and conventional drugs. [18] These types of interactions may be more common than drug-drug interactions because herbal medicines often contain multiple pharmacologically active ingredients, while conventional drugs typically contain only one. [18] Some such interactions are clinically significant, [19] although most herbal remedies are not associated with drug interactions causing serious consequences. [20] Most catalogued herb-drug interactions are moderate in severity. [21] The most commonly implicated conventional drugs in herb-drug interactions are warfarin, insulin, aspirin, digoxin, and ticlopidine, due to their narrow therapeutic indices. [21] [22] The most commonly implicated herbs involved in such interactions are those containing St. John’s Wort, magnesium, calcium, iron, or ginkgo. [21]

Examples

Examples of herb-drug interactions include, but are not limited to:

Mechanisms

The 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 factors

The 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 hepatic or 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]

Epidemiology

As of 2008, among adults in the United States of America older than 56, 4% were taking medication and or supplements that put them at risk of a major drug interaction. [30] Potential drug-drug interactions have increased over time [31] and are more common in the less-educated elderly even after controlling for age, sex, place of residence, and comorbidity. [32]

See also

Notes

  1. ↑ 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.

Related Research Articles

<span class="mw-page-title-main">Cytochrome P450</span> Class of enzymes

Cytochromes P450 are a superfamily of enzymes containing heme as a cofactor that mostly, but not exclusively, function as monooxygenases. In mammals, these proteins oxidize steroids, fatty acids, and xenobiotics, and are important for the clearance of various compounds, as well as for hormone synthesis and breakdown. In 1963, Estabrook, Cooper, and Rosenthal described the role of CYP as a catalyst in steroid hormone synthesis and drug metabolism. In plants, these proteins are important for the biosynthesis of defensive compounds, fatty acids, and hormones.

<span class="mw-page-title-main">Cimetidine</span> Medication

Cimetidine, sold under the brand name Tagamet among others, is a histamine H2 receptor antagonist that inhibits stomach acid production. It is mainly used in the treatment of heartburn and peptic ulcers.

<span class="mw-page-title-main">CYP3A4</span> Enzyme that metabolizes substances by oxidation

Cytochrome P450 3A4 is an important enzyme in the body, mainly found in the liver and in the intestine, which in humans is encoded by CYP3A4 gene. It oxidizes small foreign organic molecules (xenobiotics), such as toxins or drugs, so that they can be removed from the body. It is highly homologous to CYP3A5, another important CYP3A enzyme.

<span class="mw-page-title-main">CYP2D6</span> Human liver enzyme

Cytochrome P450 2D6 (CYP2D6) is an enzyme that in humans is encoded by the CYP2D6 gene. CYP2D6 is primarily expressed in the liver. It is also highly expressed in areas of the central nervous system, including the substantia nigra.

<span class="mw-page-title-main">CYP2E1</span> Protein-coding gene in the species Homo sapiens

Cytochrome P450 2E1 is a member of the cytochrome P450 mixed-function oxidase system, which is involved in the metabolism of xenobiotics in the body. This class of enzymes is divided up into a number of subcategories, including CYP1, CYP2, and CYP3, which as a group are largely responsible for the breakdown of foreign compounds in mammals.

Drug metabolism is the metabolic breakdown of drugs by living organisms, usually through specialized enzymatic systems. More generally, xenobiotic metabolism is the set of metabolic pathways that modify the chemical structure of xenobiotics, which are compounds foreign to an organism's normal biochemistry, such as any drug or poison. These pathways are a form of biotransformation present in all major groups of organisms and are considered to be of ancient origin. These reactions often act to detoxify poisonous compounds. The study of drug metabolism is called pharmacokinetics.

<span class="mw-page-title-main">Nortriptyline</span> Antidepressant medication

Nortriptyline, sold under the brand name Pamelor, among others, is a medication used to treat depression. This medicine is also sometimes used for neuropathic pain, attention deficit hyperactivity disorder (ADHD), smoking cessation and anxiety. As with many antidepressants, its use for young people with depression and other psychiatric disorders may be limited due to increased suicidality in the 18–24 population initiating treatment. Nortriptyline is a less preferred treatment for ADHD and stopping smoking. It is taken by mouth.

<span class="mw-page-title-main">Doxepin</span> Medication to treat depressive disorder, anxiety disorders, chronic hives, and trouble sleeping

Doxepin is a medication belonging to the tricyclic antidepressant (TCA) class of drugs used to treat major depressive disorder, anxiety disorders, chronic hives, and insomnia. For hives it is a less preferred alternative to antihistamines. It has a mild to moderate benefit for sleeping problems. It is used as a cream for itchiness due to atopic dermatitis or lichen simplex chronicus.

<span class="mw-page-title-main">Dextromethorphan</span> Morphinan antitussive and dissociative drug

Dextromethorphan (DXM) is a cough suppressant used in many cough and cold medicines. It affects serotonin, norepinephrine, NMDA, and sigma-1 receptors in the brain, all of which have been implicated in the pathophysiology of depression. In 2022, the FDA approved the combination dextromethorphan/bupropion to serve as a rapid acting antidepressant in patients with major depressive disorder.

<span class="mw-page-title-main">Naringin</span> Chemical compound

Naringin is a flavanone-7-O-glycoside between the flavanone naringenin and the disaccharide neohesperidose. The flavonoid naringin occurs naturally in citrus fruits, especially in grapefruit, where naringin is responsible for the fruit's bitter taste. In commercial grapefruit juice production, the enzyme naringinase can be used to remove the bitterness (debittering) created by naringin. In humans naringin is metabolized to the aglycone naringenin by naringinase present in the gut.

<span class="mw-page-title-main">CYP1A2</span> Enzyme in the human body

Cytochrome P450 1A2, a member of the cytochrome P450 mixed-function oxidase system, is involved in the metabolism of xenobiotics in the human body. In humans, the CYP1A2 enzyme is encoded by the CYP1A2 gene.

<span class="mw-page-title-main">Grapefruit–drug interactions</span> Drug interactions with grapefruit juice

Some fruit juices and fruits can interact with numerous drugs, in many cases causing adverse effects. The effect is most studied with grapefruit and grapefruit juice, but similar effects have been observed with certain other citrus fruits.

<span class="mw-page-title-main">CYP2C9</span> Enzyme protein

Cytochrome P450 family 2 subfamily C member 9 is an enzyme protein. The enzyme is involved in the metabolism, by oxidation, of both xenobiotics, including drugs, and endogenous compounds, including fatty acids. In humans, the protein is encoded by the CYP2C9 gene. The gene is highly polymorphic, which affects the efficiency of the metabolism by the enzyme.

<span class="mw-page-title-main">CYP2C19</span> Mammalian protein found in humans

Cytochrome P450 2C19 is an enzyme protein. It is a member of the CYP2C subfamily of the cytochrome P450 mixed-function oxidase system. This subfamily includes enzymes that catalyze metabolism of xenobiotics, including some proton pump inhibitors and antiepileptic drugs. In humans, it is the CYP2C19 gene that encodes the CYP2C19 protein. CYP2C19 is a liver enzyme that acts on at least 10% of drugs in current clinical use, most notably the antiplatelet treatment clopidogrel (Plavix), drugs that treat pain associated with ulcers, such as omeprazole, antiseizure drugs such as mephenytoin, the antimalarial proguanil, and the anxiolytic diazepam.

The erythromycin breath test (ERMBT) is a method used to measure metabolism (oxidation and elimination from the system) by a part of the cytochrome P450 system. Erythromycin produces 14CO2, and this 14CO2 can be measured to study drugs that interact with the cytochrome P450 system. Erythromycin is tagged with carbon-14 and given as an intravenous injection; after 20 minutes the subject blows up a balloon and the carbon dioxide exhaled that is tagged with carbon-14 shows the activity of the CYP3A4 isoenzyme on the erythromycin. ERMBT can be used to determine how drugs that the CYP3A4 isoenzyme metabolizes will function in a given individual.

<span class="mw-page-title-main">Bergamottin</span> Chemical compound

Bergamottin (5-geranoxypsoralen) is a natural furanocoumarin found in the pulp of pomelos and grapefruits. It is also found in the peel and pulp of the bergamot orange, from which it was first isolated and from which its name is derived.

<span class="mw-page-title-main">CYP2B6</span> Protein-coding gene in the species Homo sapiens

Cytochrome P450 2B6 is an enzyme that in humans is encoded by the CYP2B6 gene. CYP2B6 is a member of the cytochrome P450 group of enzymes. Along with CYP2A6, it is involved with metabolizing nicotine, along with many other substances.

<span class="mw-page-title-main">CYP4F2</span> Enzyme protein in the species Homo sapiens

Cytochrome P450 4F2 is a protein that in humans is encoded by the CYP4F2 gene. This protein is an enzyme, a type of protein that catalyzes chemical reactions inside cells. This specific enzyme is part of the superfamily of cytochrome P450 (CYP) enzymes, and the encoding gene is part of a cluster of cytochrome P450 genes located on chromosome 19.

<span class="mw-page-title-main">20-Hydroxyeicosatetraenoic acid</span> Chemical compound

20-Hydroxyeicosatetraenoic acid, also known as 20-HETE or 20-hydroxy-5Z,8Z,11Z,14Z-eicosatetraenoic acid, is an eicosanoid metabolite of arachidonic acid that has a wide range of effects on the vascular system including the regulation of vascular tone, blood flow to specific organs, sodium and fluid transport in the kidney, and vascular pathway remodeling. These vascular and kidney effects of 20-HETE have been shown to be responsible for regulating blood pressure and blood flow to specific organs in rodents; genetic and preclinical studies suggest that 20-HETE may similarly regulate blood pressure and contribute to the development of stroke and heart attacks. Additionally the loss of its production appears to be one cause of the human neurological disease, Hereditary spastic paraplegia. Preclinical studies also suggest that the overproduction of 20-HETE may contribute to the progression of certain human cancers, particularly those of the breast.

<span class="mw-page-title-main">Non steroidal aromatase inhibitors</span>

Non-Steroidal Aromatase Inhibitors (NSAIs) are one of two categories of aromatase inhibitors (AIs). AIs are divided into two categories, steroidal aromatase inhibitors and non-steroidal aromatase inhibitors that is based on their mechanism of action and structure. NSAIs are mainly used to treat breast cancer in women. NSAIs binding is a reversible process where NSAIs binds to the aromatase enzyme through non-covalent interactions. When aromatase inhibitors (AIs) are used to treat breast cancer the main target is the aromatase enzyme which is responsible for the high estrogen level.

References

  1. ↑ Tannenbaum C, Sheehan NL (July 2014). "Understanding and preventing drug-drug and drug-gene interactions". Expert Review of Clinical Pharmacology. 7 (4): 533–44. doi:10.1586/17512433.2014.910111. PMC   4894065 . PMID   24745854.
  2. ↑ Qato DM, Wilder J, Schumm LP, Gillet V, Alexander GC (April 2016). "Changes in Prescription and Over-the-Counter Medication and Dietary Supplement Use Among Older Adults in the United States, 2005 vs 2011". JAMA Internal Medicine. 176 (4): 473–82. doi:10.1001/jamainternmed.2015.8581. PMC   5024734 . PMID   26998708.
  3. ↑ Greco, W. R.; Bravo, G.; Parsons, J. C. (1995). "The search for synergy: a critical review from a response surface perspective". Pharmacological Reviews. 47 (2): 331–385. ISSN   0031-6997. PMID   7568331.
  4. ↑ Khan, Shahab; Stannard, Naina; Greijn, Jeff (2011-07-12). "Precipitation of thiopental with muscle relaxants: a potential hazard". JRSM Short Reports. 2 (7): 58. doi:10.1258/shorts.2011.011031. ISSN   2042-5333. PMC   3147238 . PMID   21847440.
  5. ↑ S Gonzalez. "Interacciones Farmacológicas" (in Spanish). Archived from the original on 2009-01-22. Retrieved 1 January 2009.
  6. ↑ Curso de Farmacología Clínica Aplicada, in El Médico Interactivo Archived 2009-08-31 at the Wayback Machine
  7. ↑ Malgor — Valsecia, Farmacología general: Farmacocinética.Cap. 2. en "Archived copy" (PDF). Archived from the original (PDF) on 2012-09-07. Retrieved 2012-03-20.{{cite web}}: CS1 maint: archived copy as title (link) Revised 25 September 2008
  8. ↑ 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
  9. 1 2 Marduga Sanz, Mariano. Interacciones de los alimentos con los medicamentos. on Archived 2014-07-07 at the Wayback Machine
  10. ↑ Tatro, DS. Update: Drug interaction with grapefruit juice. Druglink, 2004. 8 (5), page 35ss
  11. ↑ Valsecia, Mabel en
  12. 1 2 Elizabeth Lipp (2008-06-15). "Tackling Drug-Interaction Issues Early On". Genetic Engineering & Biotechnology News . Mary Ann Liebert, Inc. pp. 14, 16, 18, 20. Retrieved 2008-07-06. (subtitle) Researchers explore a number of strategies to better predict drug responses in the clinic
  13. ↑ IUPAC , Compendium of Chemical Terminology , 2nd ed. (the "Gold Book") (1997). Online corrected version: (2006–) " cytochrome P450 ". doi : 10.1351/goldbook.CT06821 Danielson PB (December 2002). "The cytochrome P450 superfamily: biochemistry, evolution and drug metabolism in humans". Current Drug Metabolism. 3 (6): 561–97. doi:10.2174/1389200023337054. PMID   12369887.
  14. 1 2 Nelson D (2003). Cytochrome P450s in humans Archived July 10, 2009, at the Wayback Machine . Consulted 9 May 2005.
  15. ↑ Bailey DG, Malcolm J, Arnold O, Spence JD (August 1998). "Grapefruit juice-drug interactions". British Journal of Clinical Pharmacology. 46 (2): 101–10. doi:10.1046/j.1365-2125.1998.00764.x. PMC   1873672 . PMID   9723817.
    Comment in: Mouly S, Paine MF (August 2001). "Effect of grapefruit juice on the disposition of omeprazole". British Journal of Clinical Pharmacology. 52 (2): 216–7. doi:10.1111/j.1365-2125.1978.00999.pp.x. PMC   2014525 . PMID   11488783.[ permanent dead link ]
  16. ↑ Covarrubias-Gómez, A.; et al. (January–March 2005). "¿Qué se auto-administra su paciente?: Interacciones farmacológicas de la medicina herbal". Revista Mexicana de Anestesiología. 28 (1): 32–42. Archived from the original on 2012-06-29.
  17. ↑ Gago Bádenas, F. Curso de Farmacología General. Tema 6.- Excreción de los fármacos. en Archived 2011-09-16 at the Wayback Machine
  18. 1 2 3 Fugh-Berman, Adriane; Ernst, E. (20 December 2001). "Herb-drug interactions: Review and assessment of report reliability". British Journal of Clinical Pharmacology. 52 (5): 587–595. doi:10.1046/j.0306-5251.2001.01469.x. PMC   2014604 . PMID   11736868.
  19. 1 2 3 4 Hu, Z; Yang, X; Ho, PC; Chan, SY; Heng, PW; Chan, E; Duan, W; Koh, HL; Zhou, S (2005). "Herb-drug interactions: a literature review". Drugs. 65 (9): 1239–82. doi:10.2165/00003495-200565090-00005. PMID   15916450. S2CID   46963549.
  20. ↑ Posadzki, Paul; Watson, Leala; Ernst, Edzard (May 2012). "Herb-drug interactions: an overview of systematic reviews". British Journal of Clinical Pharmacology. 75 (3): 603–618. doi:10.1111/j.1365-2125.2012.04350.x. PMC   3575928 . PMID   22670731.
  21. 1 2 3 Tsai, HH; Lin, HW; Simon Pickard, A; Tsai, HY; Mahady, GB (November 2012). "Evaluation of documented drug interactions and contraindications associated with herbs and dietary supplements: a systematic literature review". International Journal of Clinical Practice. 66 (11): 1056–78. doi: 10.1111/j.1742-1241.2012.03008.x . PMID   23067030. S2CID   11837548.
  22. ↑ Na, Dong Hee; Ji, Hye Young; Park, Eun Ji; Kim, Myung Sun; Liu, Kwang-Hyeon; Lee, Hye Suk (3 December 2011). "Evaluation of metabolism-mediated herb-drug interactions". Archives of Pharmacal Research. 34 (11): 1829–1842. doi:10.1007/s12272-011-1105-0. PMID   22139684. S2CID   38820964.
  23. 1 2 3 Meijerman, I.; Beijnen, J. H.; Schellens, J. H.M. (1 July 2006). "Herb-Drug Interactions in Oncology: Focus on Mechanisms of Induction". The Oncologist. 11 (7): 742–752. doi:10.1634/theoncologist.11-7-742. PMID   16880233.
  24. ↑ Ulbricht, C.; Chao, W.; Costa, D.; Rusie-Seamon, E.; Weissner, W.; Woods, J. (1 December 2008). "Clinical Evidence of Herb-Drug Interactions: A Systematic Review by the Natural Standard Research Collaboration". Current Drug Metabolism. 9 (10): 1063–1120. doi:10.2174/138920008786927785. PMID   19075623.
  25. ↑ Chen, XW; Sneed, KB; Pan, SY; Cao, C; Kanwar, JR; Chew, H; Zhou, SF (1 June 2012). "Herb-drug interactions and mechanistic and clinical considerations". Current Drug Metabolism. 13 (5): 640–51. doi:10.2174/1389200211209050640. PMID   22292789.
  26. ↑ Baños Díez, J. E.; March Pujol, M (2002). Farmacología ocular (in Spanish) (2da ed.). Edicions UPC. p. 87. ISBN   978-8483016473 . Retrieved 23 May 2009.
  27. ↑ Merle L, Laroche ML, Dantoine T, Charmes JP (2005). "Predicting and Preventing Adverse Drug Reactions in the Very Old". Drugs & Aging. 22 (5): 375–392. doi:10.2165/00002512-200522050-00003. PMID   15903351. S2CID   26672993.
  28. 1 2 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 Archived 2013-04-14 at archive.today
  29. 1 2 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
  30. ↑ Qato DM, Alexander GC, Conti RM, Johnson M, Schumm P, Lindau ST (December 2008). "Use of prescription and over-the-counter medications and dietary supplements among older adults in the United States". JAMA. 300 (24): 2867–78. doi:10.1001/jama.2008.892. PMC   2702513 . PMID   19109115.
  31. ↑ Haider SI, Johnell K, Thorslund M, Fastbom J (December 2007). "Trends in polypharmacy and potential drug-drug interactions across educational groups in elderly patients in Sweden for the period 1992 - 2002". International Journal of Clinical Pharmacology and Therapeutics. 45 (12): 643–53. doi:10.5414/cpp45643. PMID   18184532.
  32. ↑ Haider SI, Johnell K, Weitoft GR, Thorslund M, Fastbom J (January 2009). "The influence of educational level on polypharmacy and inappropriate drug use: a register-based study of more than 600,000 older people". Journal of the American Geriatrics Society. 57 (1): 62–9. doi:10.1111/j.1532-5415.2008.02040.x. PMID   19054196. S2CID   205703844.

Bibliography

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