PHARMACOLOGY

1. PHARMACOLOGY STUDENTS WELCOME! PROF. DR. ECE GENÇ

5. DRUGS DRUGS Synthetic Chemicals Genetic engineering products Chemicals obtained from plants or animals

6. DRUG DISCOVERY THEN

9. Biochemistry Physiology Pharmacology Chemistry Medicine A synthesis of several biomedical sciences…. …but unique in its own right

10. Pharmacology can be defined as the study of the effects of drugs on the function of living systems • In the middle of 19th century, it was born as a science → one of a host of biomedical sciences based on principles of experimentation rather than dogma • From the dawn of civilization, herbal remedies were widely used, pharmacopeias were written

11. Robert Boyle (middle 17th century) was comfortable to recommend concoctions of worms, dung, urine and the moss from a dead man’s skull • The doctors’ need to improve outcome of therapeutic intervention caused pharmacology to improve • Until the late 19th century, normal and abnormal body functioning were not understood and drug effect????? Disease and death were regarded as semisacred subjects dealt with authoritarian rather than scientific doctrines

12. Cinchona bark was recognized as an effective treatment for malaria and Lind (1765) wrote the protocols • In 1804 Johnson declared it to be unsafe until fever subsides, and recommended the use of HgCl2 it was followed for ~ 40 years

14. Pharmacologists Study Science at Every Level

15. PROGRESS OF PHARMACOLOGY Has been enormous during the recent years. • Chemistry Techniques of chemical synthesis have improved enormously • Detailed understanding of both normal and pathologic physiology and biochemistry bring mechanistic insight into disease • Virchow proposed cell theory in 1868 • The first use of a structural formula to describe a chemical compound was in 1868 • Pasteur discovered bacteria as a cause of disease in 1878 • Rudolf Buchheim created the first pharmacology institute in his own house in Estonia in 1847

16. DRUGS & PLANTS Small molecules <500Da

17. assigning functions to unknown genes, identifying inherited contributions to disease, • and synthesizing human proteins in cultured microbes of mammalian cells for use as therapeutic agents • Recombinant DNA technology permitted synthesis of proteins by various organisms (bacteria, yeast)

18. Large molecules are increasingly important • Insulin • GH • Erythropoietin • GCSF • Monoclonal antibodies IS THE TARGET DRUGABLE?

19. DRUG INVENTION HIGH THROUGHPUT SCREENING

20. The approach today relies on high-throughput screening of libraries containing hundreds of thousands or even millions of compounds for their ability to interact eith a specific molecular target or elicit a specific biological response • Automated screening procedures employing robotic systems can process hundreds of thousands of samples in just a few days, reactions are carried out in small trays containing a matrix of tiny wells (384 or 1536)

21. Can one find a drug that will have the desired effect against its target? • Does modulation of the target protein affect the course of the disease? • Does the project make sense economically?

22. PROGRESS OF PHARMACOLOGY • minimize toxicity, • optimize and vary the pharmacokinetic profiles of drugs • prove that the agents identified are in fact appropriate for clinical use

24. Drug development and approval Preclinical testing Clinical trials Post-marketing surveillance (Phase 4) Many thousands of participants In vitro studies Animal testing Long-term toxicity studies Phase 1 – normal volunteers: safety, pharmacokinetics 10-100 participants NDA IND Phase 2 – selected patients: therapeutic efficacy, dose range 50-500 participants Phase 3 – large populations of selected patients: therapeutic efficacy, safety in double blind studies a few hundred-a few thousand participants 1 to 5 years 2 to 10 years 1 year Average years

27. INVENTION OF NEW DRUGS PHASES, TIME LINES

28. COST OF DRUG INVENTION & PRODUCTIVITY

30. Subdivisions of Pharmacology • Neuropharmacology: study of the effect of drugs on components of the nervous system (brain, spinal cord, nerves) Example: treatment of Alzheimer's • Cardiovascular Pharmacology: study of the effects of drugs on heart, vasculature, kidney, nervous and endocrine systems that participate in cardiovascular function. Example: treatment of high blood pressure (hypertension)

31. Subdivisions of Pharmacology • Molecular Pharmacology: study of the biochemical and biophysical characteristics of interactions between drug molecules and those of the cell Example: Drug-Receptor Interaction • Biochemical Pharmacology: study of how drugs act with and influence the chemical ‘machinery’ of the organism Example: signal transduction through G proteins

32. Subdivisions of Pharmacology • Behavioral Pharmacology: study of the effects of drugs on behavior Example: treatment of Attention Deficit Disorders • Endocrine Pharmacology: study of drugs that are hormones or hormone derivatives Example: creation of The Pill

33. Subdivisions of Pharmacology • Clinical Pharmacology: application of pharmacodynamics and pharmacokinetics to patients with disease. Example: use of pharmacogenomics to tailor individual medical treatment • Chemotherapy: study of drugs used for treatment of microbial/viral infection and malignancies Example: treatment of cancer through anti-angiogenic agents such as bevacizumab. ANTIBODY THERAPY

34. Subdivisions of Pharmacology • Systems and Integrated Pharmacology: study of the use of whole animal approaches to best predict the efficacy of new treatments in the human. Example: use of pharmacogenomics to tailor individual medical treatment • Veterinary Pharmacology: study of the use of drugs for disease and health problems unique to animals. Example: treatment of feline leukemia (Viral) with Acemannan

35. What Pharmacology is NOT... • Pharmacy This is a separate profession responsible for the preparation and dispensation of medication. • Pharmaceutical Science