1 / 20

Drug discovery techniques - a specialist course for undergraduate pharmacologists

Drug discovery techniques - a specialist course for undergraduate pharmacologists. James A. Angus & Christine E. Wright. Department of Pharmacology University of Melbourne Victoria 3010 Australia. 2000 in vivo practical teaching – Australia & NZ. Systems covered by practicals.

felicia
Download Presentation

Drug discovery techniques - a specialist course for undergraduate pharmacologists

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript


  1. Drug discovery techniques - a specialist course for undergraduate pharmacologists James A. Angus & Christine E. Wright Department of Pharmacology University of Melbourne Victoria 3010 Australia

  2. 2000 in vivo practical teaching – Australia & NZ

  3. Systems covered by practicals

  4. Techniques used by students

  5. Current in vivo practicals – 1 • CNS/Autonomic • Rat: sedation, hypnotic effects & anaesthesia • Conscious rabbit: baroreflex & other reflexes • Mouse: routes of drug administration, sleeping times, behavioural effects • Student: ocular effects of drugs; ethanol & psychomotor function • Analgesia • Mouse: tolerance & dependence to morphine • Student: local anaesthetics • Renal • Student: diuretic drugs

  6. Current in vivo practicals – 2 • Cardiovascular • Conscious rabbit: cardiovascular control; central vs. peripheral antihypertensive drugs; renin-angiotensin • Student:b-blockers & exercise; glyceryl trinitrate • Metabolism • Mouse: pentobarbitone in liver • Student: aspirin excretion; ethanol, pharmacokinetics • Asthma • Student: Ventolin, glyceryl trinitrate & histamine • Inflammation • Guinea pig: cutaneous & systemic anaphylaxis

  7. 2002 in vivo practicalsBSc third year ≈ 2 x 30 students • Drugs affecting reflex control of blood pressure • to compare the responses to pressor & depressor agents ± sympathetic & parasympathetic cardiac nerve blockade in conscious rabbits • Angiotensin-converting enzyme inhibition • to compare the responses to angiotensin I, angiotensin II & bradykinin ± ACE inhibition in conscious rabbits

  8. Problems – 1 • Animal ethics • Pressure to decrease animal numbers • Difficult to convince that use of animals has benefits over computer simulation • Staff training • Loss of expertise • More trained demonstrators per practical • Expense & equipment • Animal cost (especially larger species) • Lack of sophisticated equipment

  9. Problems – 2 • Class sizes & time slots • eg. Melbourne University Science 3rd year students increased from 30 to 70 in last 3 years • 6 hour practicals becoming a luxury • Pressure to develop computer simulations or demonstrations for all subject areas • Student reluctance

  10. The fall & rise of in vivo pharmacology- In Vivo Pharmacology Training Group TiPS 23: 13-18, 2002

  11. “in vivo training & knowledge MUST be given proper emphasis in any pharmacology courses that are offered now & for the foreseeable future” UK 1977: BSc - all incorporated in vivo pharmacology 1997: 27 university depts. running BSc pharmacology; 9 had somein vivo training • Why: economics - too expensive staff training/skills - retired molecular biologists • Home office - society pressure • Student numbers - fees • Modular courses • Careers - pharmacology not outcome

  12. Science III - Pharmacology PracticalLent Term 1968 -Obtained from University of Sydney

  13. “Brave new post-genomic world” • Targets: • 30,000 genes to protein products • Testing: • robotics, high throughput screening • Compounds: • combinatorial chemistry & natural products • Bioinformatics: • virtual chemical libraries, computer modelling

  14. What molecular biology, in vitro studies & computer technology cannot do • Integrated response • molecule to man • Reveal the unexpected • secondary actions, selectivity • Determine the therapeutic index • Assess importance of multiple mediators • Determine pharmacokinetics • Assess safety & toxicology • Set clinical dose range

  15. bioinformatics chemistry biochemistry molecular biology electrophysiology genetics immunology histology Pharmacologist: principles of drug action integrated approach skills “.. Unique position to bring specialist knowledge together & make informed judgements on whether or not the new chemical entity has the potential to become a therapeutic agent.” Drug discovery: a multidisciplinary process

  16. Future needs • Preclinical knowledge • Proof of concept • Safety & toxicology • “Best guess” for clinical trial “Molecular revolution has led to reemphasis of the central role of in vivo pharmacology in drug discovery”

  17. Semester 1: Applied Pharmacology Techniques Quota 24

  18. Semester 2: Applied Pharmacology Techniques Quota 20

  19. Semester 2: Applied Pharmacology Techniques • Aims are to introduce: • pharmacological techniques used to evaluate the mechanism of action, as well as selectivity, of potential drug candidates both in vitro & in vivo • the theoretical & practical aspects of preclinical drug development from selection of candidate molecule through to Phase I clinical trial • lectures & tutorials to cover the theory & methods involved in each advanced technique which include: • behavioural pharmacology • in vitro preparations of cardiovascular, airway & urogenital tissues • chronic surgical instrumentation • assessment of cardiovascular & autonomic responses in vivo

  20. Teaching in vivo pharmacology Man • Integrated pharmacology • Autonomic reflexes, neurohumoral influences • Homeostasis, cardiovascular control • Inflammation, analgesia In vivo In vitro Molecule

More Related