Medical informatics Course Work: Interactions Spring Heidi Vähämaa Marjo Linja Niaz Mohammad

Transcription

1 Medical informatics Course Work: Interactions Spring 2005 Heidi Vähämaa Marjo Linja Niaz Mohammad

2 1 Introduction Our task was to develop an IT solution related to interactions between medicines. Since the field is huge there are thousands of known medicines and even more known interactions between them the focus was narrowed down to antihypertensives and the drugs interacting with them. We have gathered some examples from each class of antihypertensives and searched for medication that interact with them. The major sources in our search has been the internet and Pharmaca fennica. 1.1 Interactions It s very common and sometimes even necessary to take many pharmaceuticals simultaneously. Pharmaceutical chemicals might strengthen or weaken each other s effect and the interactions might be harmful or useful; toxicity might develop or smaller dosage is enough and thereby the occurrence of ill effects diminish. Therefore all the information about the possible interactions is important. Interaction can be synergistic or antagonistic. When the synergism of two drugs is as big as the sum of their actions the synergism is called additive and if the synergism is bigger than the sum of their actions it s called supra-additive. Physiologically this means that the absorption of the drug might change, their bonding with plasma proteins or transport might change or their secretion might change. 1.2 Hypertension Blood pressure is the cardiac output (The volume of blood discharged from the ventricle (or the heart) per minute) times total peripheral resistance. Blood pressure is called hypertension when it s more than 140/85 mmhg. The medication is selected considering other illnesses and the damage to the target organ. Half of the men in Finland between the ages 35 and 64 have hypertension and 33% of the women as well. Hypertension is influenced by the genetic effect and the way of life. The risk factors that can be changed are overweight, additional supply of sodium, excessive drinking of alcohol and insufficient physical exercise. Secondary hypertension can be caused by certain drugs like steroids or medical conditions like Cushing s syndrome. Also pregnancy or eating too much liquorice might cause hypertension temporarily Treating hypertension Drugs used in treating hypertension can be divided into 6 groups. 1. Alpha blockers Widens the peripheral arterioles 2. Beta blockers Decrease the cardiac output by decreasing the pulse rate and the contraction volume 3. ACE inhibitors Widens the blood vessels 4. Angiotensin blockers Widens the blood vessels

3 5. Diuretics Increase the secretion of sodium and water and thereby decrease the amount of exocellular fluid and the volume of plasma 6. Calcium Blockers Widens the blood vessels and decrease the cardiac output 2 Analysis When a doctor prescribes drugs for a patient he should always be aware of potential interactions between patients medication. The decissions must often be made in couple of minutes. It's essential that the doctor has proper tools for finding all the needed information. Mistakes may have catastrophic consequences for the patient. The potential interactions should be recognized based on current medication and medical conditions of the patient. All interactions consisting of pharmaceuticals drugs and conditions should be recognized: Current drugs: D1 D2 D3 D4 Matching interactions: D1 Interaction 1 D2 D3 Interaction 2 D2 Sometimes might also be useful to just check all the interactions in which the target drug is involved in. Current drugs: D1 Matching interactions: D1 Interaction 1 D2 An interaction may consist of one or more pharmaceuticals and medical conditions. Also the medicin may be a concrete drug (such as verapamil ) or a group of drugs (such as calsium channel blockers ). If an interaction involves a group, it also involves all the drugs within the group. D2 Current drugs: D2 Group 1 Matching interactions: G1 Interaction 3 D5

4 One usability requirement is that the drugs can be selected easily and that they can be identified uniquely. The brand names, however, can be omitted. Different brands may contain exactly the same active chemical compound. The requirements can be satisfied either by identifying the pharmaceuticals 1) by their active compounds. The problem is, however, that the compounds may have different names in different languages. The names can be also easily misspelled. 2) by their ATC code (anatomical therapeutic chemical [1]). Cardiac and vessel disease medication C Selective cardiac calsium channel blockers C08D Calsium channel blockers C08 Phenylalkylamins C08DA Verapamil C08DA01 ATC code consists of five parts: 1) letter 2) two digits 3) letter 4) letter 5) two digits Example: Verapamil: C 08 D A 01 Within the atc system, the drugs are organized in groups. Also the groups have unique codes, but they differentiate from the drug codes as the last identifiers are empty. The more general the group is, the less identifiers it has within its atc. Example: Calsium channel blockers: C 08 The structure of ATC-codes can be Figure 1: An example of the relationship considered as a tree. In the tree the between the ATC codes and the groups of drugs subgroups of drugs form subtrees and the drugs represent leaves. (figure 1) Compared to the number of all possible interactions, there are only few known interactions. Most drugs probably don't interact with each other. However, for those drugs who do have a therapeutically signicant interactions, it's also essential to distinguish between the different types of interactions. The interactions can be organized in following main categories: Recommended combination Neutral combination (can be also interpreted as no harmful interactions ) Risky combination, should be monitored. Dangerous combination, should be avoided. Possible interaction, however not tested. Also the drugs are affected various ways within the interactions: Increase effect Reduce effect No change in effect Other (for example, a new kind of side effect)

5 3 The Interactions We gathered approximately 150 interactions between the antihypertensives and other medication and medical conditions. Figure 2 shows these interactions. The types of the interactions are distinguished by colour; green stands for recommended, yellow for pay attention, red for avoid, black for neutral and blue for not tested enough, possible. Figure 2: Visualization of the database.

6 4 Database As simplest, the application can be a graphical user interface attached to a simple interaction database. Essential components of the interactions are drugs and the medical conditions. Figure 3 shows an interaction sketched as ER diagram.the diagram can be easily converted to a database. atc effect DRUG m has n compound description type description INTERACTION name description id CONDITION m has n Figure 3 ER converted to a database

7 4.1 Tables DRUG A single entry in table drug may represent a single drug (for example, verapamil ) or a group of drugs (for example, calsium channel blockers ). atc Drugs can be identified based on a ATC code that consists of five parts. Compound Name of the active compound. For groups, this field contains the group title. Description The medicine may also contain a short textual description. DRUGINTERACTION A table to establish a relation between DRUG and INTERACTION atc The drug to be added to the interaction. Id Id number of the interaction. Effect The change in the effect of this drug within the interaction. 0: up 1: down 2: no effect 3: other INTERACTION A single interaction may involve one or more medicines and medical conditions. Type The type of interaction 0: Recommended combination 1: Neutral 2: Pay attention (risk exists) 3: Avoid 4: Not tested but possibility exists id A unique id number for distinguishing interactions from each other. Description A short textual description. CONDITIONINTERACTION A table that links CONDITION to INTERACTION. - condname Name of the condition to be linked. - intid Id number of the interaction. CONDITION This table ensures that the same writing is always used for the same medical condition. Name A unique name for the condition. Description An optional short description. 4.2 Required features in user interface List of drugs to be considered List of medical conditions to be considered An ability add and remove items on previous two lists. A button that initiates the search for interactions between the selected items A result list representing matching interactions. An output text area for textual description of interactions.

8 5 The application Java was selected as the implementation language because our group had most experience in using java development tools. The program was implemented as stand-alone application. Also an applet based user interface was considered, but the idea was never concretized because a network based application would had required a database on public ip-address. However, if needed, the application can be easily converted later into a network based one. Interaction Base main uses creates db uses gui The database was implemented as an access file. The current implementation does not have take multiuser case into consideration, as it is highly improbable that several users would utilize the application on the same computer. In addition, the end users will use the database as a data source, no updates are performed on the database. In principle, the multiuser circumstances should not affect the functionality of the application. However, this cannot be guaranteed because the case is not tested. Figure 4 Packages The application consists of two main components: graphical user interface (package gui) and database connection (package db). Access point of the application lies in package main. Graphical user interface utilizes the database via interface provided by db. Db possesses the actual database connection through ODBC (figure 4). 5.1 db It's probable that same drugs and interactions are reviewed several times within the same session. For efficiency related reasons, db stores the loaded interactions and drugs into a cache. There's no real risk that the database would change meanwhile since a standard end user does not normally modify the database. All drug/interaction related information does not have to be loaded at once: Single drug involves several interactions and correspondingly single interaction involves several drugs and medical conditions. The elements are loaded in a greedy manner: on the first request, the corresponding object is created however, no data is loaded into the object from the database. The only initial information contained by the object will be its unique id code (atc code for drugs, id number for interactions, name for medical conditions). If more information about the object is requested later, the object will send a request to the databaseconnection, which will concequently load and set the data.

9 5.2 gui There are two major classes within gui package: InteractionBrowser and Editor. InteractionBrowser implements the actual application, as the Editor operates as a convenience component that provides a consistent way for adding drugs and interactions to the database. 5.3 main Package main consists of single class Main which provides the starting point of the application. The application can be launched from command prompt with argument read to initiate InteractionBrowser or write to initiate the Editor. DatabaseConnection InteractionBrowser gui Drug implements DrugInstance DrugInteraction db Interaction Implements InteractionInstance Editor creates Main creates Condition main MedicalCondition implements Public classes & interfaces Private classes Packages Figure 5 Detailed description of packages Ideas for the future: More drugs and interactions to the database. Ability to find drugs based on their names (English/Finnish/Swedish) Possibility to search drugs based on current conditions and medication.

10 6 Manual 6.1 Installation requirements - Windows (tested in XP and 2000 pro) - JRE or higher [2] - Microsoft Access ODBC driver (delivered with microsoft office) 6.2 Installation 1) Copy the contents of the zip into a proper folder on your hard disk. 2) Select from control panel (ohjauspaneeli) > administrator tools (valvontatyökalut) > ODBC 3) select sheet system (or user) data sources DSN (järjestelmätietolähteet) 4) Click add... 5) Select Microsoft access driver 6) Name the database as interactionbase 7) Select the database db1.mdb from the folder to which you copied the zip contents. 8) Ok. 5.3 Running the browser Double click on the browser -icon. The window should appear:

11 6.3.1 Finding interactions Add to the list each pharmaceutical that the patient is taking. The pharmaceuticals are added by typing the ATC code on the text field (on the top) and clicking Add medicine Correspondingly, add each medical condition that concerns the patient. The conditions can be selected from the combo box. Click Find to see all the interactions that consist of selected items. The results are listed on the combo box Results. The interactions can be viewed by selecting items from the result list. Also all the interactions concerning one drug can be brought to the result list by double clicking the code of the drug on the search list. 6.4 Running the Editor Medical conditions can be added to the database currently only manually (table conditions ). However, for the drugs and the interactions there exists a convenience editor. Double click on editor icon. The Editor window will open Adding drugs: Select tab Medicines You can either write the ATC code or Finnish or Swedish name for the active compound. If the checkbox look from register is selected, the corresponding property is searched from text file atc.txt.

12 6.4.2 Adding interactions: - Select tab interactions. Select each involved drug and condition from the lists by double click. For each drug, you must specify the type of effect within the interaction (whether the effect of the drug is increased, reduced, remaining the same or something else). Select type of the interaction from the combo box list on upper right corner. You can also write a short description on the text area on the right. Click Add interaction. The database is updated when the editor is closed Adding medical conditions So far there's no graphical user interface for adding medical conditions to the database. This has to be accomplished manually on the database (db1.mdb) table condition. Notice that this editor supports only one user at a time. That's why it's extremely important to coordinate the usage of the database with care. If two persons update the database simultanously, there's no way to combine the two versions afterwards. 7 References [1] ATC codes [2] java runtime environment jre-1.5.0_03-oth-jpr&siteid=jsc&transactionid=noreg