INTRODUCTION TO PHARMACOLOGY

1. INTRODUCTION TO PHARMACOLOGY Pharmacist Jeanette Jasper Tenga (Mrs. J. Senkondo) Nov 2011

2. Common ground for the task ahead • Why do you want to become a medical professional? • What would you like to be? • What do you think are going to be your responsibilities? (First as a medical student and later as a medical professional). • What are your expectations during your time learning Pharmacology?

3. Important tips • Do not walk in the dark during your medical training • Define where you want to go • Think seriously on how to achieve your goal and have the right attitude towards learning, your lecturers, leaders and others • In other words, create a reason to learn

4. Important tips..... • To whatever you do, consider 3 things: • interest • time • concentration N.B: Fall in Love with Pharmacology

5. Challenges in Clinical Pharmacology for tomorrow’s doctors • The number of licensed medicines is rapidly increasing and doctors are increasingly expected to prescribe medicines that are less familiar to them • Pace of new drug development is accelerating rapidly as a result of advances in molecular biology and mapping of the human genome

6. Challenges in Clinical Pharmacology for tomorrow’s doctors... • Patients are taking more medicines than before, increasing the complexity of their treatment regimen and the potential for drug interactions • Newer drugs, capable of targeting previously untreatable conditions, are often more powerful but also more toxic • The expansion of evidence-based medicine and health technology assessment has enabled the beneficial and adverse effects of drugs to be more accurately quantified

7. Challenges in Clinical Pharmacology for tomorrow’s doctors... • There are more sources of opinion and disinformation available to patients and doctors (increasing access to the internet) • Marketing activites of the pharmaceutical industry are a potential threat to cost-effective prescribing decisions

8. Clinical Pharmacology Training at HKMU • Semester 3 • Semester 4 • All in MD2

9. Clinical Pharmacology Training at HKMU ..... • Semester 5 (MD3) • Only protected time to concentrate on learning the scientific basis for the principles of therapeutics and gaining core knowledge and understanding about drugs • Clinical rotations • Witness and learn about the use of drugs in practice and gain skills in prescribing, drug administration and attitudes towards the use of drugs

10. The burden of factual knowledge is high in Pharmacology • You may feel overwhelmed by the number of drugs described in pharmacology text books • It is important to understand general pharmacological principles, and to appreciate the pharmacology of the main classes of drugs rather than attempting to memorise details of individual drugs • Specific therapeutic drugs are best learned about near a patient’s bedside

11. For each of the commonly used drugs in our setting we expect the following from you: • Know the name and class • Have an understanding of the mechanism of action • Recognise the appropriate indication for use • Know the appropriate route, frequency and duration of administration • Know the important contraindications, potential interactions and adverse effects • Know how to monitor the drug’s effects • Be able to explain the salient features of all the above to the patient

12. General Learning Objectives • To produce graduates who are competent to prescribe safely, effectively and cost-effectively. • To provide the appropriate framework to be able to assimilate information about new drug developments that will occur throughout a professional career

13. Course Content General Principles of Pharmacology Chemical Mediators Systems Pharmacology Antimicrobial and Cancer Chemotherapy Special Topics

14. Lecturers’/Teachers’ Responsibility • We have a responsibility to the public, to employers and the profession to make sure that graduates are fit to practise; and prescribing drugs is a key component of medical practice • WE ARE NOT INTERESTED IN FAILING ANY ONE!

15. Some Key Definitions • Pharmacology: • the study of the effects of chemical substances/drugs on the function of living systems OR • the study of the manner in which the function of living systems is affected by chemical agents N.B: Knowledge of the normal & abnormal functioning of the body is necessary

16. Some Key Definitions.... • Drug: a chemical substance of known structure, other than a nutrient or an essential dietary ingredient, which, when administered to a living organism, produces a biological effect NB: like most definitions, this one has its limits. E.g. There are a number of essential dietary constituents, such as iron and various vitamins, that are used as medicines.

17. Drugs may be: • Synthetic chemicals • Chemicals from plants or animals • Products of genetic engineering (biotechnology) • To count as a drug, the substance must be administered intentionaly to produce a certain desired biological effect. i.e the substance must be administered as such, rather than released by physiological mechanisms. • Many substances, e.g. Insulin or thyroxine, are endogenous hormones but are also drugs when administered intentionally

18. Drug… • Many drugs are not used in medicines but are nevertheless useful in research tools. • The word drug is often associated with addictive, narcotic or mind-altering substances- an unfortunate negative connotation that tends to bias uninformed opinion against any form of chemical therapy. • We will focus mainly on drugs used for therapeutic purposes but also describe important examples of drugs used as experimental tools.

19. A medicine: chemical preparation which usually but not necessarily contains one or more drugs, administered with intention of producing a therapeutic effect. • Medicines usually contain other substances (excipients, stabilisers, solvents etc) besides the active drug, to make them more convenient to use

20. Poison • Poison: a substance that causes death or harm when introduced into or absorbed by a living organism. • Scientifically, a poison is any substance taken into the body by ingestion, inhalation, injection, or absorption that interferes with normal physiological functions. • Virtually any substance can be poisonous if consumed in sufficient quantity; therefore the term poison more often implies an excessive degree of dosage rather than a specific group of substances. • Although poisons fall strictly within definition of drugs they are not used in therapy

21. Question! • What is the difference between a Drug and a Medicine????

22. Development of Pharmacology as a Scientific Discipline Overview: The objective of this introduction to pharmacology session is: • to explain how pharmacology came into being and evolved as a scientific discipline and • describe the present day structure of the subject and its links to other biomedical sciences

23. Development of Pharmacology as a scientific discipline.... • Ancient prescientific therapeutics • Herbal remedies were widely used • No application of scientific principles to therapeutics • Dogma used to explain therapeutic effects (magic, vital forces) • Pharmacology in the 19th century • As a science Pharmacology was born in the mid-19th century, out of increasing skills among doctors at clinical observation and diagnosis but being ineffectual when it came to treatment • A need to improve outcome of therapeutic interventions by doctors provided impetus for pharmacology

24. Until the late 19th century, knowledge of the normal and abnormal functioning of the body was too rudimentary to provide even a rough basis for understanding drug effects; • Disease and death were regarded as semi sacred subjects, appropriately dealt with by authoritarian, rather than scientific doctrines. • Clinical practice often displayed an obedience to authority and ignored what appear to be easily ascertainable facts.

25. motivation for pharmacology (i.e. understanding what drugs can and cannot do) came from clinical practice, however, the science could be built only on the basis of secure foundations in physiology, pathology and chemistry which fortunately developed • 1847, first pharmacology institute created in Estonia (Rudolf Buchheim, in his own house) • In its begginnings, before the advent of synthetic organic chemistry, pharmacology concerned itself exclusively with understanding of the effects of natural substances (plant extracts and a few toxic chemicals e. g. Mercury, arsenic) • Purification of active compounds from plants was possible through early development in chemistry

26. 1805, Friedrich Serturner, a young German apothecary, purified morphine from opium, and other substances quickly followed, and, even though their structures were unknown, these • Compounds showed that chemicals, not magic or vital forces, were responsible for the effects that plant extracts produced on living organisms. • 1858, Virchow proposed the cell theory • the first use of structural formula to describe chemical compounds was in 1868 • 1878, Bacteria as a cause of disease were discovered by Pasteur

27. Early pharmacologists focused most of their attention on such plant-derived drugs as quinine, digitalis, atropine, ephedrine, strychnine etc ( many of which are still used today and maybe will have become old friends by the time you graduate as a medical doctor).

28. Pharmacology in the 20th and 21st centuries • Beginning in the 20th century, the growth of synthetic chemistry, and resurgence of natural product chemistry revolutionalised the pharmaceutical industry and the science of pharmacology • New synthetic drugs (barbiturates, local anaesthetics) appeared • Era of microbial chemotherapy began with the discovery by Paul Ehrlich in 1909 of arsenical compounds for treating syphilis

29. Gerhard Domagk, discovered sulfonamides, the first antibacterial drugs in 1935 • Chain and Florey developed penicillin during the Second World War, based on the earlier work of Fleming • By this time, pharmacology had really established its identity and status among the biomedical sciences • Physiology was also making rapid progress particulary in relation to chemical mediators • Many hormones, neurotransmitters and inflammatory mediators were discovered in this period

30. The realisation that chemical communication plays a central role in almost every regulatory mechanism in living systems, established a large area of common ground between physiology and pharmacology (for interaction between chemical substances and living systems were exactly the interest of pharmacologists from begining) • 1905, Langley first proposed the concept of ‘receptors’ for chemical mediators, and this was quickly taken up by pharmacologists e.g. Clark, Gaddum, Schild and others • The Receptor concept and technologies developed from it, have had a massive impact on drug discovery and therapeutics

31. Biochemistry also emerged as a distinct science in early 20th century • Discovery of enzymes and delineation of biochemical pathways provided yet another framework for understanding drug effects • The picture of pharmacology that emerges from this brief glance at history is of a subject evolved from ancient prescientific therapeutics, involved in commerce from the 17th century onwards and which gained respectability by donning the trappings of science as soon as this became possible in the mid-19th century.

32. The pharmaceutical industry has become very big business and much pharmacological research nowadays takes place in a commercial environment. • The figure in the next slide shows the development of pharmacology

34. The figure in the next slide shows Pharmacology today with its various subdivisions. • NOTE: interface disciplines (brown boxes) link pharmacology to other mainstream biomedical disciplines (green boxes) • Read and understand the various subjects & terminologies

35. Figure 1-2 Pharmacology today with its various subdivisions. Interface disciplines (brown boxes) link pharmacology to other mainstream biomedical disciplines (green boxes).

36. Alternative therapeutic principles • Allopathy • Homoeopathy • Acupuncture • Herbalism • Aromatherapy • H/W Read on the above

37. Modern medicine relies heavily on drugs as the main tool of therapeutics • Other therapeutic procedures e.g. surgery, diet, excercise etc. Are also important but are less commonly used • Therapeutic principles outside the domain of science are currently gaining ground as ‘alternative’ or ‘complementary’ or ‘holistic’ medicine • The problem: they reject the medical model which attributes disease to an underlying derangement of normal function that can be defined in biochemical or structural terms, detected by objective means and influenced beneficially by appropriate chemical or physical interventions.

38. They focus instead mainly on subjective malaise, which may be disease associated or not. • Abandoning objectivity in defining and measuring disease lead to; • Departure from scientific principles in assessing therapeutic efficacy and risk • Unfortunately, practices can gain public acceptance without satisfying any of the criteria of validity that would convince a critical scientist, and that are required by law to be satisfied before a new drug can be introduced into therapy.

39. Reference Books to be used • Pharmacology by Rang & Dale • Basic Pharmacology by R. W. Foster • Others

40. THANK YOU FOR LISTENING!

41. WELCOME TO THE NEW WORLD OF PHARMACOLOGY