Drug interaction

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Drug interactions (also drug interactions ) can occur when different drugs are taken at the same time . The desired pharmacological effect can thereby be strengthened, weakened or canceled. In addition, adverse drug effects ("side effects") can occur. The risk is particularly high when using many different drugs ( polypharmacy or multi- medication ).

Demarcation

Drug interactions are considered separately from chemical or physical incompatibilities that can occur when multiple drugs are present in the same syringe or infusion solution at the same time . Such incompatibilities can lead to chemical reactions with precipitation , discoloration and the formation of new substances.

Mechanisms

There are several possible mechanisms that lead to interactions:

A pharmacokinetic interaction is an interaction that indirectly (via induction or inhibition at cytochrome P450 ) or directly (intermolecular) influences the bioavailability of the drugs.

  • Pharmacodynamic interaction: Combined drugs affect the same target organ or the same regulatory cycle.
    • The effect is increased or decreased. This is mostly done pharmacodynamically, but can also be caused kinetically, for example if one substance leads to a second being absorbed to a greater extent. In the case of effect enhancements, a distinction can be made between additive and superadditive reinforcement.
    • There are completely unexpected effects.

The likelihood of interactions increases with the number of medications taken at the same time and thus especially with increasing age of elderly patients. If, for example, a blood pressure lowering agent is strengthened in its effect by another drug, the blood pressure drops more sharply. This means that the dose of one or both drugs has to be reduced, especially with long-term use. If the interaction between several drugs leads to relevant damage to the body, for example kidney or liver damage, then this must lead to a change in medication.

Interactions are not uncommon, even with complementary therapy methods. For example, laxatives and flaxseed can reduce the absorption of oral therapeutic agents, and green tea can chemically interact with bortezomib .

Classic drug interactions are interactions between drugs that can lead to toxic effects or to a reduction in the therapeutic effect through inhibitory or activating (inductive) effects on the enzyme cytochrome P450 . Interactions (enzyme effects) via cytochrome P450 3A4 are particularly frequent. With the target structures of the modern “ small molecules ” in the signal cascades, there is a multitude of possible interactions, the relevance of which is not yet clear. Among other things, the importance of the inhibition of the enzyme cytochrome P450 2D6 in tamoxifen treatment is known. Not only serotonin reuptake inhibitors (certain substances used to treat depression) can seriously impair the effectiveness of this adjuvant breast cancer therapy.

Medicines that act inductively on cytochrome P450 include, for example, the antibiotics griseofulvin and rifampcin, the anti-epileptic carbamazepine, the anti-inflammatory drug phenylbutazone, the psychotropic drug Hypericum, the proton pump inhibitor omeprazole and the hypnotic drug phenobarbital.

Food and drug interactions

In addition to drugs, food and beverages can also interact with drugs. The standard example is the mutual enhancement of the effects of alcohol and sedatives . Alcohol, nicotine and caffeine are to be rated as pharmacologically active substances in connection with ingested medication. Smoking leads to the accelerated breakdown of many medicinal substances and thus to a shorter effect, black tea reduces the absorption of many active substances into the body. Taking monoamine oxidase inhibitors are tyramine -containing foods avoided.

Not only St. John's wort , ginger , ginkgo , garlic or liquorice are inducers of a cytochrome P450 enzyme, while grapefruit juice , valerian , turmeric , star fruit or ginseng inhibit the enzyme. Consumption of foods of the first group reduces the absorption and effectiveness of many drugs, but can improve absorption in the case of fat-soluble active substances. The consumption of foods of the second group inhibits the breakdown of many medicinal substances and thus leads to a prolonged effect.

Interaction testing

Finding potential interactions is made possible by the package insert of the drug, the summary of characteristics contained therein , with the help of the associated specialist information , via drug directories such as the Red List or by special databases that are nowadays built into modern clinic and patient management software as so-called drug information systems. The doctor can use so-called electronic files and the automated creation of a prescription or medication plan, which was introduced by the law for secure digital communication and applications in health care as well as changes to other laws of December 21, 2015 ( Federal Law Gazette I p. 2408 ) is to provide a complete overview of all interactions of the selected drugs recorded in the database. The question of non-prescription drugs such as B. St. John's wort preparations seen z. T. can cause significant interactions with other preparations and drugs. This is not always reflected in these information systems.

In a statement from the DIHK of October 1, 2015 on this new draft law, it says: "In addition, mandatory information of the medication plan for the patient should be defined in the prescription, including active ingredients, interaction (interactions) with other medications, storage instructions, restricted reactions, recommendations for use, etc. " This also leaves the question open as to whether this information is only intended for the doctor or, in the course of transparency and relevance for the patient himself, has to be given to him as part of the medication plan.

Many pharmacies offer drug interactions. In Germany, unwanted drug or drug interactions have been listed since the Federal Ministry of Health announced the action plan for drug therapy safety . In some cases, interactions are also recorded in the course of phase IV studies .

Drug interactions databases are e.g. B. National Library of Medicine DailyMed , the Japan Pharmaceutical Information Center (JAPIC), the DrugBank , the KEGG DRUG database , the BindingDB , the PharmGKB , the SIDER database and the WOMBAT (World of Molecular Bioactivity) database . The ABDA - Federal Association of German Pharmacists' Associations maintains the ABDA databases in its subsidiary Avoxa , on which DIMDI is also based. PSIAC is a database for drug interactions.

Social relevance

The following model calculation was made for the drug-related problems in Germany, of which undesirable interactions represent a part: Number of prescriptions per year: 470 million, of which 2% with drug-related problems: 9.4 million, of which 30% are potentially hazardous to health: 2.82 million, of which 30% with hospitalization : 0.846 million, of which 30% can be avoided through drug documentation: 253,800, 7 days in hospital per case: 1.78 million days, 291 euros costs per day: thus 518 million euros costs that could have been avoided. Up to 7% of hospital stays are due to drug interactions.

literature

  • Ingolf Cascorbi: Drug Interactions: Principles, Examples and Clinical Consequences . In: Dtsch Arztebl Int . No. 109 (33-34) , 2012, pp. 546-556 ( review ).
  • Torsten Kratz, Albert Diefenbacher: Psychopharmacotherapy in old age. Avoidance of drug interactions and polypharmacy. In: Deutsches Ärzteblatt. Volume 116, Issue 29 f. (July 22) 2019, pp. 508-517.

Individual evidence

  1. ↑ Heiner Berthold: Clinical Guide to Drug Therapy . 2nd Edition. Urban and Fischer, Munich / Jena 2003, ISBN 3-437-41151-9 , pp. 106 f . ( limited preview in Google Book search).
  2. ↑ a b I. Cascorbi: Drug interactions principles, examples and clinical consequences. In: Deutsches Ärzteblatt international. Volume 109, number 33–34, August 2012, pp. 546–555, doi : 10.3238 / arztebl.2012.0546 . PMID 23152742 . PMC 3444856 (free full text).
  3. ↑ Torsten Kratz, Albert Diefenbacher: Psychopharmacotherapy in old age. Avoidance of drug interactions and polypharmacy. In: Deutsches Ärzteblatt. Volume 116, Issue 29 f. (July 22) 2019, pp. 508-517, p. 509.
  4. ^ Pharmaceutical newspaper online .
  5. ↑ See for example Torsten Kratz, Albert Diefenbacher: Psychopharmakotherapie im Alter. Avoidance of drug interactions and polypharmacy. In: Deutsches Ärzteblatt. Volume 116, Issue 29 f. (July 22) 2019, pp. 508-517.
  6. ↑ Torsten Kratz, Albert Diefenbacher: Psychopharmacotherapy in old age. Avoidance of drug interactions and polypharmacy. In: Deutsches Ärzteblatt. Volume 116, Issue 29 f. (July 22nd) 2019, pp. 508-517, here: p. 508.
  7. ↑ H. Petri: CYP450 interactions: interactions of SSRI antidepressants. In: Deutsches Ärzteblatt. Volume 115, 2015, Supplement: Perspectives in Neurology. P. 33 f.
  8. ↑ Torsten Kratz, Albert Diefenbacher: Psychopharmacotherapy in old age. Avoidance of drug interactions and polypharmacy. 2019, p. 510 f.
  9. ^ A b C. S. Won, NH Oberlies, MF Paine: Mechanisms underlying food-drug interactions: inhibition of intestinal metabolism and transport. In: Pharmacology & therapeutics. Volume 136, Number 2, November 2012, pp. 186-201, doi : 10.1016 / j.pharmthera.2012.08.001 . PMID 22884524 . PMC 3466398 (free full text).
  10. ↑ DA Flockhart: Dietary restrictions and drug interactions with monoamine oxidase inhibitors: an update. In: The Journal of clinical psychiatry. Volume 73 Suppl 1, 2012, pp. 17-24, doi : 10.4088 / JCP.11096su1c.03 . PMID 22951238 .
  11. ↑ a b H. H. Tsai, HW Lin, A. Simon Pickard, HY Tsai, GB Mahady: Evaluation of documented drug interactions and contraindications associated with herbs and dietary supplements: a systematic literature review. In: International journal of clinical practice. Volume 66, Number 11, November 2012, pp. 1056-1078, doi : 10.1111 / j.1742-1241.2012.03008.x . PMID 23067030 .
  12. ↑ MJ Dolton, BD Roufogalis, AJ McLachlan: Fruit juices as perpetrators of drug interactions: the role of organic anion-transporting polypeptides. In: Clinical pharmacology and therapeutics. Volume 92, number 5, November 2012, pp. 622-630, doi : 10.1038 / clpt.2012.159 . PMID 23033114 .
  13. ↑ Thomas Effert: Molecular Pharmacology and Toxicology: Biological Foundations of Medicines and Poisons, p. 24 . Springer, Berlin 2006, ISBN 978-3-540-21223-2 .
  14. ^ Opinion on the draft law for secure digital communication and applications in the health sector (e-health law), draft law of June 22, 2015. DIHK , October 1, 2015, archived from the original on December 22, 2015 ; accessed on September 27, 2019 .
  15. ^ B. Percha, RB Altman: Informatics confronts drug-drug interactions. In: Trends in pharmacological sciences. Volume 34, number 3, March 2013, pp. 178-184, doi : 10.1016 / j.tips.2013.01.006 . PMID 23414686 . PMC 3808975 (free full text).
  16. ↑ Electronic drug safety check saves costs, Der Hausarzt, 20/06, p. 34 according to communication platform in health care, May 2001.