Unit 1a Computers in Pharmacy new.pptx

Applications of computers in pharmacy

1. Computers in Pharmaceutical Research and Development Dr. Lakshmi M. Pharm., Ph.D.

2. History of computers in pharmaceutical research and development. History of Computers in Pharmaceutical Research Origin of Computers in Pharmaceutical Research Mid 19th Century Early 1960s Early 1970s Between 1975 and 1985 The 1990s

3. Introduction Today computers becomes so ubiquitous in pharmaceutical research and development that it may be hard to imagine a time when there were no computers to assist the medicinal chemist or biologist. A quarter-century ago, the presence of a computer on the desk of every scientist and company manager was not even contemplated. But nowadays, computers becomes absolutely essential for generating, managing, and transmitting the information. The journey of computers in pharmaceutical companies starts in the early 1940s.

4. Contd … There were several scientific and engineering advances that made it possible to design and develop a molecule through a computational approach. With the advancement of science medicinal chemists starts understanding the relationship between the chemical structure of a molecule with its molecular and biological activity (SAR). Therefore if someone could predict the molecular properties by doing calculations , then he/she might be able to predict which structures should be investigated in the laboratory.

5. Contd … At the same time Fischer’s proposed the hypothesis of lock and key concepts to understand how a drug molecule exerts its pharmacological/biological activity through binding to and/or inhibiting some biomolecule/ receptor in the body. Upto 1950s, the Pioneering research in the field of Quantum mechanics attacked the problem of linking the relationship between electronic structure and biological activity. These developments leads to the introduction to QSAR (Quantitative Structure Activity Relationships) which basically assigned molecular descriptors in describing biological activity

6. Contd … Molecular descriptors are the calculated or experimental numerical value that describes the chemical structure of that molecule. A good part of this work was published in the 1963 book by Bernard and Alberte Pullman of Paris, France, which fired the imagination of what might be possible with calculations on biomolecules . Therefore gradually computer became a tool for scientific innovation , which was initially designed for accounting applications.

7. Contd … Earlier up to the 1960s, drug discovery was carried out through Random Drug Design i.e. by “trial and error”. The medicinal chemists manually collect and read the literature related to patented products and used their creativity and expertise to synthesize therapeutically active compounds. The synthesized compounds were then tested by in/out house microbiologists/biochemists for their biological potential along with another related bioactivity for which research was being conducted at that time. The most potent compound discovered led to a series of other structures which leads to the creation of a table comparing the potency and activity, which finally led to one compound (drug) and after development known as a pharmaceutical product .

8. Contd … However, Random drug Design involved time and cost and sometime were inaccurate. Today computational biology plays a central role in innovation which remarkably reduced the time interval for finding potential drug candidates by matching molecular structure databases against target molecules and finding an appropriate match thus generating a lead molecule. This will lead to a Rational Drug Design approach.

9. Computational Chemistry: The Beginnings at Lilly In the early 1940s, the first computers to have stored programs of scientific interest were acquired. One of these was an IBM 650; it had a rotating magnetic drum memory consisting of 2000 accessible registers. The programs, the data input, and the output were all in the form of IBM punched cards. Apart from lilly other MNC groups like Abbott, Upjohn and Dow Chemical’s also took the initiative to explore using computers for drug discovery. These initiatives involved either adding resources with computer proficiency or training in-house scientists on the new methodology.

10. Contd … It was carried out by Lilly’s research statistics group under Dr. Edgar King. It was not until 1968, when Don Boyd joined the second theoretical chemist in the group, that the computers at Lilly started to reach a level of size, speed, and sophistication to be able to handle some of the computational requirements of various evaluation and design efforts. The first breakthrough in computational drug discovery was at Lilly which revealed the relationship between the calculated electronic structure of beta-lactam ring of cephalosporins and antibacterial activity.

11. Germination: The 1960s Other MNCs also initiated these efforts, however, some of these companies lost out and quit due to lack of management support. It was Lilly, whose persistence paid off as it established its base in such expertise. The companies at that time invested in hardware and software from the money they gained from the sale of their products. The computer models used at that time were the IBM360 and the 370 series and input methods slowly advanced from punch cards to dumb terminals (terminals or PCs that had no local processing capability). The industry hired computational chemists from academia for their initial ventures into using computers for drug discovery.

12. Contd … In addition, the other chemists educated using computers were the X-ray crystallographers. One of the largest computers then in use by theoretical chemists and crystallographers was the IBM 7094 . Support staff operated the tape readers, card readers, and printers. Programs were still written in FORTRAN, followed by the well-known MMPI program used for molecular mechanics. Finally in regard to software, one program that came from the realm of crystallography to overcome the tedious task of restoring the deck and replacing the unused torn cards.

13. Contd … This program was ORTEP (Oak Ridge Thermal Ellipsoid Program), which was the first widely used program for (non-interactive) molecular graphics. With these developments the pharmaceutical industry began transitioning to using molecular mechanics, QSAR, and statistics rather than restricting to quantum mechanics. However, on the other hand, this will lead to a war situation between the medicinal and computational chemists . For the computational chemists, it was quite easier to change a nitrogen atom to carbon or any other element or to attach a subsistent at any position in whatever stereochemistry would make the compound more active. Computationally, it was easy to change a six-member ring to a five-member ring and so on.

14. Gaining a Foothold: The 1970s Lilly management took a positive step in 1970s, by opening communication channels between the two groups and organizing a series of workshops for medicinal chemists to operate computational programs to perform calculations on molecules. The same activity was followed by Merck and Smith Kline group which conducted a similar workshop. However, despite these initiatives, the medicinal chemists were slow to accept this computational approach because sometimes the computational methods failed to predict the biologically active compounds and therefore medicinal chemists would start dismissing the idea of computational chemistry as a whole.

15. Contd … In the 1970s two new computer resources were launched namely the Cambridge Structural Database (CSD) and the PDB (Protein Data Bank). Both of these were found as a boon for Computational chemists because these databases would yield more therapeutically active compounds as more compounds were deposited into them. Placing more powerful in-house machines (IBM 360 and 370 series) made it easier and more secure to submit jobs and retrieve output. But output was still in the form of long printouts.

16. Growth: The 1980s The decade of the 1980s was when the pharmaceutical companies noted the development of the IBM personal computer (PC) for application of various modern computational chemistry approaches like quantum chemistry, molecular mechanics, molecular simulations, QSAR, statistics and molecular graphics etc. The first technical advances computer was development as VAX 11/780 computer by Digital Equipment Corporation (DEC) in 1979. Later in 1984, the Apple Macintosh introduced a set of new standard of user friendliness to the computer. These machines were great at word processing, graphics and managing small laboratory databases and suddenly all medicinal chemists took a liking to it.

17. Fruition: the 1990s In addition, the advancements of software front also made most medicinal chemists enthusiastic about computers. The important ones are electronic mail, networking capability advancement, ChemDraw , and molecular graphics for 3D molecular structures. The 1990s was a decade of fruition because the computer- based drug discovery work of the 1980s yielded a large number of NCEs (new chemical entities) reaching the pharmaceutical marketplace.

18. Contd … During this time the Apple Macintoshes were well liked by scientists. However, in 1994 Apple lost its lawsuit against Microsoft regarding the similarities of the Windows graphical user interface (GUI) to Apple’s desktop design. With the advancement of computational drug discovery, the attitude towards the computational chemists changed, and therefore CADD become an indispensable factor in the process of drug discovery and development ever since for providing assistance to the medicinal chemist.

19. A pplications of Computers i n pharmacy Right now computers and pharmacy go hand in hand. Drug and patient database management. Order entry systems, billing; purchasing. Drug information. Automated dispensing units. Used in various studies i.e. PK/PD Today we can exchange health information and provide services across geographic, time and social boundaries.

20. Computer & Medical Education Computers have revolutionized the way education is handled in today’s world. I n medica l education, computers are particularly useful because there is such a need for learning and presenting large amounts of data, getting and comparing accurate study and test results, and effectively monitoring patients.

21. Health informatics Health care informatics or medical informatics is the intersection of information science, computer science, and health care. It deals with the resources, devices, and methods required to optimize the acquisition (gaining), storage, retrieval, and use of information in health and biomedicine. Health informatics tools include not only computers but also clinical guidelines, formal medical terminologies, and information and communication systems. It is applied to the areas of nursing, clinical care, dentistry, pharmacy, public health, and biomedical research

22. Computer-aided design of drugs A further refinement of new drug design and production was provided by the process of computer-aided design (CAD). With the availability of powerful computers and sophisticated graphics software, it is possible for the medicinal chemist to design new molecules and evaluate their effectiveness.

23. Presentations The field of medicine often relies on complex definitions of conditions and procedural techniques. If you are an educator, use the computer to show your medical students PowerPoint presentations that simplify the large amounts of text often needed in medical science. Stick to the basics in visual presentations. You also may use computers to present video data of medical policies or procedures, or for slide shows of diseases or traumas and their treatments.

24. Research Papers If you are doing a medical research study, you can use the computer to write your findings, format a paper for publication, find relevant studies on the Internet or print posters for medical conferences. If you use the Internet, stick to reputable information sources such as electronic versions of medical journals. Being able to write these kinds of papers is crucial in establishing your credibility as a medical professional because they show that you have an understanding of one or more medical topics and are able to conduct research and present information.

25. Simulations Because medicine involves hands-on work, medical students need to practice procedures before they do the procedure for real on a patient. Use computer programs that simulate surgery and other procedures to meet this need.

26. Instrumentations Instruments play a vital role in the analysis of various samples. Va r i o u s software a r e d e s i g n e d running of instruments. Examples: UV-visible spectroscopy by UV Probe. FTIR by IR Solution HPTLC by Wincats HPLC by Empower

27. Informational Storage Computers can store massive amounts of data. Use a computer or personal digital assistant to take and store notes on any patients you may see as you go on supervised rounds. This makes it much easier to find the medical information you need when discussing the patient and reduces the physical amount of papers and texts you need to carry with you. This is very important in medicine, since efficiency and ease of referencing medical information impacts the speed and accuracy of patient treatment.

28. Testing and Self Evaluation Use computers to take tests on medical subjects or to quiz yourself on medical data. The advantage of this is that you can get immediate feedback and do not need to depend on your instructor to review information or to find out how well you have learned. If you use this method, keep your tests or reviews short and use them often rather than having huge long tests and reviews. You are more likely to retain information if you use it frequently, and in medicine, you'll also be called on to pull many medical facts daily from memory.

29. Drug Information Services Pharmaceutical companies are responsible for providing updated, relevant information on the efficacy, safety , and quality of drugs to medical professionals and finally to patients. To fulfill this responsibility, they developed a drug information database system to manage various information generated during the development of new products and after the launch of the products. This system is incorporated into an online network system and can be directly accessed by thousands of people all over the world.

30. Information System in The Pharmaceutical Industry An information system (IS) is any combination of information technology and people's activities using that technology to support operations, management, and decision-making. Advanced pharmaceutical companies are realizing that the implementation of information management technologies in their operations can greatly enhance their chances for success by reducing their time-to-market and enhancing efficiency in their production runs.

31. 3D Printing in Medicine & Formulation Three-dimensional printing (3DP) technology relies on computer aided designs to achieve unparalleled flexibility, time-saving, and exceptional manufacturing capability of pharmaceutical drug products. The process involves 3D proto-typing of layer-by-layer fabrication (via computer-aided design models) to formulate drug materials into the desired dosage form. 3DP in pharmaceutical drug delivery is anticipated to excel tremendously in the area of personalized medicines.

32. Packaging and Labeling Computers play a vital role in packaging and designing of creative labels. Packaging takes 2D designs and transforms them into printed, tactile 3D creations—it’s an incredibly effective way of bringing a strong branded look to a product, or helping the consumer to commit to purchasing.