Drug effects in clinical chemistry

Drug treatment can alter the results of clinical chemical tests.

The findings are not seldomly unexpected and misleading.

There are even some reports of mistreatment of the patients due to misunderstanding.
There are two main reasons why drugs can effect laboratory test results:

A) In vitro- by analytical interferens. 
The drug or the drug metabolite can interfere the analytical reaction:
”Drug Effects in Clinical Chemistry Methods” 
Josef Breuer et al. Eur J Clin Chem Clin Biochem1996;34:385-386 
The aim of a symposium with European experts was to establish a list 
of drugs (on terapeutic levels and above) that would indicate interference 
to clinical chemistry methods in serum and plasma. 
The following agents were chosen: 
Acetaminophen, Acetylcysteine, Acetylsalicylic acid, Ampicillin, Ascorbic acid, Calciumdobecilate, Cefoxitin, Cyclosporine, Heparin, Ibuprofen, Intralipid, Levodopa, Methyldopa, Metronidazole, Phenylbutazone, Rifampicin,Tetracycline, Theophylline. 
The expert panel used the following criteria to select 
candidates for testing of drug interference in urine testing: 
-Typical (high) urine concentration 
-typical test interference in urine 
-Common drugs 
-Relevance in vivo 
-Drugs absorbing light at methods wavelength 
Selected candidates were 
Acetaminophen, N-Acetyl cysteine, Acetylsalicyl uric acid(metabolite) 
Aminosalicylic acid, Ascorbic acid, Calciumdobecilate,Na2- Cefoxitin, 
Gentamycine sulfate, Ibuprofen, Levodopa(metabolit), Methyldopa, 
Ofloxacine, Phenazopyridine, Tetracyclin 

Every year about 10 millions test strips for urinary investigations are sold in Sweden.
Many patients eat gramdoses of vitamin C (Ascorbic acid) leading to falsely low values for glucose,hemoglobin and nitrite in urine. Some patients and doctors beleave that vitamin C can cure urinary tract infections. However, it might be that the effect of the vitamin is limited to disturbance on the test results and not necessary a treatment of the disease.
B) In vivo- by biological or pharmacological effects.

These can be regular and affect all patients or irregular, which means that only a few patients are suceptible. Examples of regular effects of drugs is the elevation of the enzyme
gammaglutamyl-transferase in serum (S-GT)  or Carbohydrate-deficient Transferrin in serum (S-CDT) in alcoholic.
However, it is important for the clinicians to be aware of the fact that nearly all patients with epilepsy who are treated with drugs also have elevated S-GT-values. Other causes for elevation of gammaglutamyl-transferase are dextropropoxyphen, herbal teas and in rare cases disulfiram (Antabus). Several hundred drugs have been reported
to increase aminotransferases in serum. The scientific literature concerning effects of drugs on clinical laboratory tests is very extensive. In fact there is an information pollution today. The Swedish Society for Clinical Chemistry and the National Corporation of Swedish Pharmacies continuously collect and evaluate important references in a database (DECC).

In Sweden we have collected and evaluated scientific references on dug effects on laboratory test results since 1972.

The first book "Läkemedels påverkan på laboratorieundersökningar" was published by Apoteksbolaget, Stockholm in 1977.

It has been extended, translated to English and sent out to central laboratories in all the Nordic countries


The following rewiew was published by S P HALLORAN in Annals of Clinical Biochemistry 1997: 

A 1993 book review of Nils Tryding's compendium of drug interferences praised the work and looked forward to the next edition and the chance to admire a further cover designed by Joan Miro'. The seventh edition will not disappoint the connoisseur of the Spanish artist or the jobbing clinical chemist who has come to rely on this tome as the definitive compilation of drug interferences.  The 6500 references which support the work are published as a supplement leaving 551 pages to chronicle the interferences in a tried and tested format. For the uninitiated, the book commences with a scholarly exposition of the principles of drug interference followed by a handy table of pharmacokinetic data of the most troublesome drugs and then an alphabetical list of interferences by drug and by test. The short explanatory comments which accompany each reference turn an unhelpful and uncritical list into a valuable source of advice. 

Technology has not passed the authors by and with a PC version and World Wide Web update available  can any-one responsible for clinical interpretation afford not to have this database within easy access?" 

The problem of drug effects in clinical practice has been reviewed in
Tidsskrift Norsk Lægeforening.

We continuously update a database containing clinical important inferences and biological effects of drugs on biochemical and hematolgical laboratory investigations.
The 7th edition of the book 
Drug Effects in Clinical Chemistry, Editors: Nils Tryding, Christer Tufvesson and Oswald Sonntag, ( ISBN 91-85574-38-4 ISSN 0282-5783, Pp. 551 and 364) was published in Stockholm 1996 by the National Corporation of Swedish Pharmacias, Pharmasoft and Swedish Society for Clinical Chemistry. It contains 6500 different literature references and can be ordered from Apotektsbolaget, Förlagsavdelningen, S-10514 Stockholm. 

Medical literature contains an enormous amount of references concerning drug influences on laboratory test results. The total number of different entries in our database is now nearly 20,000. 
We continuously reevaluate and update the content. 

The database D.E.C.C.(Drug Effects in Clinical Chemistry) The system is a computer version of the book of the same name.

It allows you to start your selection from any of the following - Systems, Components, Drugs/Substances, Tradenames or Effects. 
Having made a selection you can further subselect until you have found the required information. For more information on obtaining D.E.C.C. and for some screenshots of the system please contact  nils@tryding.se.  


For more information about the book Drug effects in clinical chemistry 1996  please read the preface ->



At the 12th European Congress of Clinical Chemistry, MEDLAB97, which took place in Basel Switzerland, August 17-22, 1997 we demonstrated the database at the workshop "Drug interferences in clinical chemistry" For an abstract see Basel 97. The DECC project was presented in Uppsala on the joint ISAP/EMEA-workshop in 1999.
The database has been demonstrated in different parts of Europe e.g. in Holland, Belgium, France (at seversal meetings in Pont-a-Mousson) , Italy (Ischia and at ATB congresses in Milan), Poland,Spain (Barcelona),Estonia, Russia (St Petersburg), Austria (Wien), Check Republik (Prag), Hungary, Denmark, Finland, Iceland, Norway and also in China (during an IFCC education journey).
There is an important practical application of evidance based information on drug effects on laboratory test results in hospital care in Turku Finland including the knowledge base multimedica.
 The collaboration between DECC and multimedica was presented at the IFCC-WorldLab'99  Conference in Firenze Italy  on  9 June 1999. 


Kailajarvi M.1, Forsstrom J.J.1, Gronroos P.1, Takala T.1, Irjala K.1, Tryding N.2 
1) Central Laboratory, Turku Univ. Central Hospital, Turku (Finland) 
2) , Ahus (Sweden) 
In clinical chemistry, the information concerning drug effects amounts to 30,000 entries. There is a real pollution 
of information. For nearly 30 years, Nils Tryding has studied and evaluated the available scientific literature and 
collected about 7,000 relevant references. We have now improved the quality of the information further by 
systematically reviewing the literature. As a result, detailed information on drug effects is now available in the 
Drug Laboratory Interference (DLI) knowledge base, which includes the ATC-number of the drug, studied population, level of documentation, clinical significance etc. At Turku University Central Hospital, a link between patient medication data and laboratory data has been built. All wards storing patient medication data in the 
hospital information system will automatically be warned of clinically significant drug effects on laboratory test 
results. A PC program available in the hospitals local data network offers access to more detailed information. 
The alerts sent to the wards are regarded useful by the clinicians. Reminders on the clinically important effects, 
e.g., the increasing effect of heparin on serum free thyroxine and the decreasing effect of glucocorticoids on serum thyrotropin concentration, reduce misinterpretation and unnecessary further examination.

The fact that drugs can alter many laboratory test results in clinical practice has been discussed in detail in the publication: Clin Chem Lab Med 1999 ;37:573-92 

Towards common reference intervals in clinical chemistry. 
An attempt at harmonization between three hospital laboratories in Skane, Sweden.
Bäck SE, Nilsson JE, Fex G, Jeppson JO, Rosen U, Tryding N, von Schenck 
H, Norlund L 
Department of Clinical Chemistry, Central Hospital, Kristianstad, 

The population sample of the Kristianstad survey, a reference intervals survey in the county of Kristianstad, was used to establish new reference intervals in clinical chemistry at the laboratories of the Central Hospital in Kristianstad, the University Hospital in Lund and the University Hospital in Malmo. Three-hundred and fifty nine subjects, male and female, aged 20-80+ years, were invited to participate in the study, with a participation rate of 70%. Up to 70 analyses were performed on each subject, general clinical chemistry parameters in all three laboratories, specialized analyses where available. 
Separate a priori exclusion criteria (including the use of drugs) were defined for each test. 
In addition, the test pattern of each individual was evaluated for signs of preclinical disease. 
Twelve cases of preclinical disease were discovered and clinically confirmed.
Details on all test methods are presented along with information concerning instruments used, calibration 
procedures, methods of calculation and obtained reference intervals. 
Although the methods were in general calibrated against acknowledged reference materials, in some instances 
differences were found that made common reference intervals across all laboratories impossible. Problems relating to the practical use of international recommendations and the establishment of reliable reference intervals are discussed. 
Farmacological Congress Älvsjö Stockholm October 9th 2000:
When do drugs affect the diagnostic procedure ?
Nils Tryding 
Abstract of the presentation :  

Referenses: 1)Drug effects in clinical chemistry ,7e upplagan, Apoteksbolaget, Stockholm, 1996. 
2) Kailajarvi M, Takala T, Gronroos P, Tryding N, Viikari J, Irjala K,Forsstrom J 
Reminders of drug effects on laboratory test results.
Clinical Chemistry 2000 ;46:1395-400.

Central Laboratory and Department of Medicine, Turku University Central 
Hospital, Kiinamyllynkatu 4-8, FIN-20520 Turku, Finland. 
Box 57, SE-29621 Åhus, Sweden. 
Medical Informatics Research Centre in Turku (MIRCIT), Kiinamyllynkatu 4-8, FIN-20520. 
Drug Laboratory Interference (DLI) knowledge base  (http://www.multimedica.com/en/) 

Drug effects on laboratory test results are difficult to take into account without an online decision support system. In this study, drug effects on hormone test results 
were coded using a drug-laboratory effect (DLE) code. The criteria that trigger the reminders were defined. To issue reminders, it was necessary to write a computer 
program linking the DLE knowledge base with databases containing individual patient medication and laboratory test results. During the first 10 months,  11% of the results from hormone samples were accompanied by one or more DLE reminders. 
The most common drugs to trigger reminders were glucocorticoids, furosemide, and metoclopramide. 
Physicians facing the reminders completed a questionnaire on the usefulness of the reminders. 
All respondents considered them useful. 
In addition, DLE reminders had caused 74% of respondents to refrain from additional, usually performed examinations. 
In conclusion, drug effects on laboratory tests should always be considered when interpreting laboratory results. 
An online reminder system is useful in displaying potential drug effects alongside test results. 

On 24 October 2003 we  presented the database on Drug Effects in Clinical Chemistry (DECC) on the EQUALIS meeting in Upplands Väsby concerning Clinical Chemistry in Primary Care.
Nils Tryding 
Box 57, SE-296 21 Åhus.  nils@tryding.se 
URL: www.tryding.se

In Sweden there is a new edition of Läkemedelsboken with a special chapter concerning drug effects on laboratory test results Läkemedel och laboratorieresultat.
The important compilation Effects of Drugs on Clinical Laboratory Tests, 5th Edition 2002
by Donald S.Young
The "Effects" books are now available as a fully searchable, online database. Click on the link to visit the Website and sign up for a FREE two-week trial subscription.

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AACC ANNOUNCES: Youngs’s Effects Online Adds European “Effects” in Merger with Tryding’s Drug Effects in Clinical Chemistry


Washington, DC, July 12, 2006 – Young’s Effects Online is a “dashboard” to the peer-reviewed literature on the effects of drugs, diseases, pre-analytical conditions and herbs on clinical laboratory tests.  It represents the life work (30+ years) of one of the world’s leading pathologists, Dr. Donald S. Young, MD, PhD, of the University of Pennsylvania.


In Europe, during the last 30 years, Dr. Nils Tryding, MD, PhD, has been compiling a similar database focusing on drug interactions – Drug Effects in Clinical Chemistry.


For the first time, Drs. Young and Tryding have agreed to merge their databases under the American Association of Clinical Chemistry’s (AACC’s) umbrella to create a global resource.  The joint publications will represent thousands of “first” effects for the US market.


In this age of intensified international travel and globally available pharmaceuticals, a worldwide “effects” resource provides lifesaving capabilities available nowhere else. During the beta testing of this site, 10% of the cardiologist changed their patients’  prescriptions based on information they found in “Young’s Effects Online.”


Fulfilling both the authors’ and AACC’s goal to advance global health through clinical chemistry, the new, merged “Effects” database will be made freely available to the developing world.


The merger ceremony toke place at AACC’s Annual Meeting on Monday, July 24, 2006, 2:00 pm at McCormick Place Convention Center, room 128, Chicago, IL.



Young’s Effects Online institutional subscription begins at $120 per year for up to 40 queries per month and allows anyone from a single institution to have access to the web-based information, which contains over 5,000 laboratory tests and over 135,000 interactions at www.fxol.org.  For more information contact subscriptions@fxol.org or call Laura Fillmore at 1-866-595-5055.

Part of the merged database was presented at the annual meeting of Swedish Society for Clinical Chemistry in Borås, Sweden on May 11, 2007


 AACC’s members develop and perform tests conducted in hospital laboratories, clinics, medical centers and other health care settings.  For more information on AACC, visit http:// www.aacc.org

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AACC ANNOUNCES:     Young’s Effects Online Now Merged with Nils Tryding’s Drug Effects in Clinical Chemistry


Washington, DC, July 1, 2007 – Young’s Effects Online is a “dashboard” to the peer-reviewed literature on the effects of drugs, diseases, preanalytical variables, herbs, and natural products on clinical laboratory tests. The life-saving information helps professionals determine the cause of anomalous lab tests, and represents the life work (30+ years) of one of the world’s leading laboratory physicians, Donald Young, MD, PhD, of the University of Pennsylvania.


In Europe, during the same period, Nils Tryding, MD, PhD, has been compiling a similar database focusing on clinically important effects of drugs in clinical chemistry, published as Drug Effects in Clinical Chemistry (see www.tryding.se).  For the first time, these two important databases have been merged under the AACC umbrella to create a unique global resource including over 160,000 interactions and some 5,000 laboratory tests. The joint online publication represents thousands of “first” effects for the US and global market, as well as the addition of thousands of generic international drug names and additional disease information supplementing that accessible by ICD9 code.


In this age of increased international travel and globally available pharmaceuticals, a worldwide “Effects” resource provides lifesaving information available nowhere else. For that reason, together with IFCC, AACC is making the new, merged “Effects” database freely available to the developing world.


Young’s Effects Online subscription begins at $140 per year for up to 40 queries per month and allows anyone from a single institution to have access to the information at www.fxol.org.  For more information on subscribing, contact subscriptions@fxol.org or 866-595-5055.




AACC is a leading professional society dedicated to improving healthcare through laboratory medicine. Its nearly 10,000 members are clinical laboratory professionals, physicians, research scientists, and others involved in developing tests and directing laboratory operations. AACC brings this community together with programs that advance knowledge, expertise, and innovation. AACC is best known for the respected scientific journal Clinical Chemistry, the award-winning patient-centered web site Lab Tests Online, and the world’s largest conference on laboratory medicine and technology. Through these and other programs, AACC advances laboratory medicine and the quality of patient care. For more information on AACC, visit www.aacc.org