YR1 Lecture 1H - Introduction to Pharmacology - Prof Gerald Muench 2022 (1).pdf

INTRODUCTION TO PHARMACOLOGY Yr 1 2022 Prof. Gerald Münch Pharmacology Unit School of Medicine Western Sydney University Learning Objectives Define pharmacology and its subdivisions Explain the concept of chemical, generic and brand names of pharmaceutical products Describe the role of TGA and ADEC...

INTRODUCTION TO PHARMACOLOGY Yr 1 2022 Prof. Gerald Münch Pharmacology Unit School of Medicine Western Sydney University Learning Objectives Define pharmacology and its subdivisions Explain the concept of chemical, generic and brand names of pharmaceutical products Describe the role of TGA and ADEC Outline the process of new drug development Discuss the four different phases of clinical development of drugs Explain the concept of drug scheduling YOU need this BOOK !! Rang and Dales Pharmacology Latest version: 9th edition Introduction https://www.slideshare.net/babithadevu/note-introduction-to-pharmacology/2 Pharmacology and its subdivisions Rang et al., 2003. Pharmacology, Figure 1.2, Pg 5. https://www.slideshare.net/babithadevu/note-introduction-to-pharmacology/8 The first drugs were derived from plants Opium poppy Fox glove Ginkgo Papaver somniferum Digitalis spp. Ginkgo biloba http://www.faculty.ucr.edu/~legneref/botany/medpic.ht Use: Pain Heart disease Cognitive disorders History of Pharmacology The age of natural substances (up to 1900) – Initially, therapeutic agents were plants or plant extracts – e.g. traditional Chinese medicine in the east, and ancient Greek medicine in the West, Aruveda and Australian bush medicine https://www.youtube.com/watch?v=I1Rxg5wgl5M&ab_channel=Pa mWoodward Snake bit medicine – Australian Bush Medicines The age of synthetic chemical drugs (1900 onwards) – In the 20th century modern chemistry and chemical technology started developing rapidly – mass production of synthetic drugs The age of biological drugs (1980 onwards) – In the last few decades biotechnology has led to use of genetically modified microorganisms in production of various human endogenous proteins/peptides (recombinant DNA technology) – e.g. insulin Timeline for Major Pharmaceutical Events Bullock et al., 2007. Fundamental of Pharmacology (5th edition). Fig 1.1, Pg 4. Recombinant proteins and antibodies (biologicals) Few and expensive examples 4 different types of drug names Chemical name: derived from its chemical structure (eg. N-acetyl-para-aminophenol); descriptive but usually long and difficult to remember and use Generic or non-proprietary name: given by the developer, usually simplified chemical name, not registered (eg. paracetamol); easier to remember Brand, trade or proprietary name: invented to be easy to remember; it is registered and patented (eg. Panadol , Dymadon , Tylenol , Panamax , Paralgin , Tempra and Parmol; all for paracetamol ) Problems with Brand Names One drug can potentially have unlimited number of brand names It is practically impossible to remember/use all of them Brand names of the same manufacturers can vary from one country to another Brand names for very different drugs may sound similar leading to mistakes in prescribing/dispensing (eg. Anaprox-Aropax, Feldene-Teldene) Consequently, there is encouragement for prescribers and pharmacists to use generic names instead of brand names Control over Drug Use in Australia Several Federal as well as State/Territory acts and regulations deal with control of drugs Issues covered include categorisation of drugs, licensing, general restrictions and conditions, prescribing, labeling, advertising, manufacturing, packing, storage, supply and administration of drugs Some examples Commonwealth – Therapeutic Goods Act 1989 – Therapeutic Goods Regulations 1990 – Narcotic Drugs Act 1967 – National Health Act 1953 New South Wales – Poisons and Therapeutic Goods Act 966 – Poisons and Therapeutic Goods Regulations 1994 Government Regulatory Bodies Government department in Australia that has responsibility for drug control is Department of Health (www.health.gov.au) Therapeutic Goods Administration (TGA) – the main Commonwealth drug regulating authority in Australia (www.tga.gov.au) TGA maintains Australian Register of Therapeutic Goods (ARTG) – official list of approved drugs, remedies, supplements and medical devices (around 64,000 entries) (www.tga.gov.au/australian-register-therapeuticgoods) Listed Medicines All medicines manufactured for supply in Australia must be listed or registered in the ARTG, unless they are specifically exempt or excluded Listed medicines are considered to be of lower risk than registered medicines; the majority of listed medicines are self-selected by consumers and used for self-treatment Listed medicines are assessed by the TGA for quality and safety but not efficacy – this means that the TGA has not evaluated them individually or requested their evaluation to see if they work Registered Medicines Medicines assessed as having a higher level of risk must be registered (as opposed to listed) The degree of assessment they undergo is rigorous and detailed, with manufacturers being required to provide comprehensive safety, quality and efficacy data Registered medicines can be non-prescription (low risk) and prescription (high risk) Complementary medicines (also known as 'traditional' or 'alternative' medicines) may be either listed or registered, depending on their ingredients and the claims made Most complementary medicines are listed in the ARTG Listed and Registered Medicines New since 2020: Assessed listed medicines http://www.tga.gov.au/ Assessed listed medicines (evidence based complementary medicines) In 2020, the TGA has implemented a new 'assessed listed medicines' pathway for sponsors to enter their products in the Australia Register of Therapeutic Goods (ARTG). To get on that list, the TGA undertakes pre-market assessment of efficacy supporting the proposed indications. In short: The company has to prove that the (herbal/complementary) medicine works – e.g. with clinical trials. https://www.tga.gov.au/assessed-listed-medicines TGA lists first AUST L(A) herbal product On 26 May 2021, Caruso’s Prostate EZE Max became the first herbal complementary medicine to receive Aust L(A) listing. This decision calls into question the evidence assessment undertaken by the TGA. Caruso’s Prostate EZE Max contains herbal extracts of Prunus africana (Pygeum), Serenoa repens (Saw palmetto extract), Epilobium parviflorum (willowherb), Cucurbita pepo (pumpkin seed oil) and lycopene (found in tomatoes and some other red fruits and vegetables). The TGA-assessed indication is, “For the relief of nocturia (nighttime urinary frequency) associated with medically diagnosed benign prostatic hypertrophy (BPH)”. https://insightplus.mja.com.au/2021/21/tga-lists-first-aust-la-herbal-product-but-wheres-the-evidence/ Drug Development Pharmaceutical industry is worth worldwide more than $250 billion/year Cost of developing a new drug can be $200-500 million Drug companies need 1-2 new drugs every 3-4 years to remain financially viable Investment in research and development of drugs is rather considered risky On average it takes more than 10 years to bring a newly discovered active compound to market Drug Development Phases of Drug Development In vitro in vivo (animals) in vivo (humans) Drug discovery and development (Drug R & D) https://misciwriters.com/2019/11/15/from-the-lab-to-your-medicine-cabinet-a-timeline-of-drug-development/ Clinical Trials For drugs which will be registered, human clinical trials must demonstrate efficacy and safety Clinical trials generally go through several phases: – phase 1 – small number of healthy human volunteers (normally 2080) to determine safety and tolerability – phase 2 – small number of patients (normally 100-300) to determine efficacy (compared with existing drugs or placebo) and detailed dosage information – phase 3 – full scale multicentre randomised double blinded controlled clinical trial (normally 1000-3000) where investigational new drug is compared to established therapy or placebo – phase 4 – obligatory post marketing surveillance to detect any rare or long-term adverse effects Poisons Standard Drug Scheduling/Poisons Standard All recommendations are contained in Standard for the Uniform Scheduling of Drugs and Poisons (SUSDP). Also called the Poisons Standard. The Poisons Standard consists of decisions regarding the classification of medicines and poisons into Schedules for inclusion in the relevant legislation of the States and Territories. The Poisons Standard also includes model provisions about containers and labels, a list of products recommended to be exempt from these provisions, and recommendations about other controls on drugs and poison. Scheduling is a means of controlling drug availability to the public The criteria for classification include toxicity, abuse potential, safety and the actual need for the chemical Most drugs are scheduled 2, 3, 4 or 8. Schedules 1 and 2 S1 – UNUSED except Victoria where – it contains poisons of plant origin which can be dangerous to health (currently some TCM herbs) – these are available only from registered practitioners S2 – PHARMACY MEDICINE: available to the public from pharmacies; a pharmacist’s advice is available if required  Examples: some cough/cold preparations, some antihistamines, some analgesics/anti-inflammatory drugs, worm tablets, antifungal creams Schedules 3, 4 & 8 S3 – PHARMACIST ONLY MEDICINE: available from a pharmacist or medical/dental practitioner without a need for prescription  Examples: insulin, asthma aerosols, weak topical corticosteroids S4 – PRESCRIPTION ONLY MEDICINE: supplied only under prescription from medical/dental practitioner; these preparations are stored in a dispensary  Examples: most drugs S8 – CONTROLLED DRUG: prescription only drugs that may produce addiction or dependence: stored in a locked cabinet  Examples: opioid analgesics, amphetamine preparations Sources of Information Official sources  Australian Pharmaceutical Formulary  Australian Pharmaceutical Handbook  British Pharmacopoeia (BP) & United States Pharmacopoeia (USP)  Martindale: The Complete Drug Reference (UK) Semi-official sources  MIMS Annual and Bi-monthly drug registers (printed and electronic CD form, as well as online after subscription)  National Prescribing Service, www.nps.org.au  Australian Prescription Products Guide (printed and electronic CD form; online for free - http://www.appco.com.au/appguide/)  Mosby’s Drug Consult (available in printed and electronic CD form) References Rang, H.P., Dale, M.M., Ritter, J.M. and Moore, P.K. (Ed). Pharmacology (7th ed.). Edinburgh: Churchill Livingstone. Bullock, S., Manias, E. & Galbraith, A. (Ed). (2007). Fundamentals of Pharmacology (5th ed.). Sydney: Pearson Education