Introduction to Pharmacology (2023) KK PDF

No need to memorise most things here – this is just introduction; this first lecture is like ‘story telling’. Just enjoy it! You will be informed during lecture, which are the important points / take home messages to understand INTRODUCTION TO PHARMACOLOGY Year I, Medical D...

No need to memorise most things here – this is just introduction; this first lecture is like ‘story telling’. Just enjoy it! You will be informed during lecture, which are the important points / take home messages to understand INTRODUCTION TO PHARMACOLOGY Year I, Medical Doctor Program 2023/2024 PROFESSOR DR AIDA HANUM GHULAM RASOOL (MBBS,PhD) Disclaimer: i) Pictures in this lecture handout for Year 1 Medical Students of Universiti Sains Malaysia is for educational purposes only & not for profit. i) Contents of this lecture are relevant for year 2023/2024  LECTURE OUTLINE Definition pharmacology & drugs Major divisions of Pharmacology: Pharmacodynamic & pharmacokinetics Disciplines of pharmacology Drug development Drug nomenclature – innovator, generic. ? Fake drugs Some common terms in pharmacology Drug sources  Pharmacology: Branch of medicine concerned with drugs Use Mechanism DRUGS How of action body handles it Drugs—chemical / substances used to modify physiological or pathological states for benefit of recipient. May be used for prevention, diagnosis & treatment. Major divisions of pharmacology—(need to know definition below) 1. Pharmacokinetics. 2. Pharmacodynamics Pharmacodynamics (what drug does to the body)—deals with mechanism of action, effects of drug use Pharmacokinetics (what the body does to the drug)—deals with drug dose, routes of administration & absorption, distribution, metabolism, excretion. Disciplines in Pharmacology include — 1. Clinical pharmacology. 2. Toxicology 3. Pharmacogenetics, pharmacogenomics 4. Pharmacognosy 5. Pharmacoepidemiology 6. Pharmacology based on organ systems Etcetera…  Clinical pharmacology: application of pharmacological principles for patient care/in humans Toxicology: deals with unwanted/bad effects of drugs. E.g. poisoning & adverse effects, management of poisoning  Pharmacogenetics: Genetic variation in humans & their effects eg differing responses to drugs Pharmacognosy: Use of medicinal substances from biological origin (often plants, can also be other natural sources) Pharmacoepidemiology. Study on the effects of drugs in large numbers of people / population Pharmacology based on organ systems: cardiovascular pharmacology, psychopharmacology, neuropharmacology, immunopharmacology etc.  DRUG DEVELOPMENT Substances approved as drugs must fulfill two requirements: I) Effective against disease for which it is used II) Meet safety criteria, tested in animal & human Often, getting approval takes several years. Drug versus supplements, traditional medicine! Drugs, must undergo tests to make sure safe & efficacious. Supplements e.g herbs & vitamins, traditional preparations, do not have to be tested for efficacy. Should be safe. Both drugs & supplements needs to be registered with MOH / KKM PROCESS OF DRUG DEVELOPMENT (no need to remember) Step 1: Discovery & development. Step 2: Preclinical Research Step 3: Clinical Research Step 4: FDA Review Step 5: FDA Post-Market Safety Monitoring  DRUG DEVELOPMENT PROCESS IND – investigational new drug NDA (new drug application) Innovator drug sold Step 1 Step 2 Step 3 (humans) Step 4 Step 5 New drug Preclinical Phase 1 Phase 2 Phase 3 Post discovery testing marketing safety years 3.5 1-2 2-4 4-6 1.5 monitoring Experimental 20-100 100-300 1000-3000 (tissue volunteer disease disease FDA /animal) / disease subjects subjects Review purpose Safety & Safety & Efficacy Verify Large scale biological dosage & side efficacy, manufactur activity effects monitor ing, adverse distribution effects , education, long term use Percent of compounds 70% 30% 27% 20% get through Innovator drug approved for use End of patent period Patent period of innovator drug Post-marketing Generic surveillance, Bioequivalent studies drugs pharmacovigilance assessed, ongoing registered, & Bioequivalent studies marketed Step 1: Discovery & development A promising compound undergo experiments on: How it is absorbed, distributed, metabolized, excreted. Potential benefits & mechanisms of action. The best dosage & way to give the drug (route) Side effects & toxicity Step 2: Preclinical Research Laboratory & animal testing to answer safety issues Performed before testing in people, whether it can cause serious harm Two types of preclinical research are: - In vitro: outside living organism e.g in tissue/cells - In vivo: in the living organism After preclinical testing, researchers review their findings & decide whether the drug should be tested in people.  Step 3: Clinical Research / clinical trials – no need to memorise! Drugs tested on people to make sure they are safe & effective Phase 1: small number of subjects (20 - 100 healthy volunteers or people with disease) Purpose: safety & dosage Phase 2: Up to several hundred people with the disease Purpose: efficacy & side effects Phase 3: up to thousands of people with disease (about 300 to 3,000) Purpose: efficacy & monitoring of adverse reactions FDA then examine submitted data & make decision to approve or not Phase 4: after drug approved by FDA (Post-Market Safety Monitoring). Purpose: safety & efficacy  Step 4: FDA review FDA examine submitted data (from phase 1,2,3) & make a decision to approve or not Step 5: FDA Post-Market Safety Monitoring FDA monitors drug safety once products available for use by the public. The true picture product’s safety takes time; may involve years after approved. Reports of problems / adverse effects will be reviewed  INNOVATOR DRUGS Innovator drug = proprietary name = trademark brand name drug layperson: ubat original New drug approved by authorities (FDA) & first marketed Patented by the company that produces it, who has done numerous research on the drug. E.g.Clarityne (contains the active ingredient loratidine) Innovator drug protected by patent when first marketed, meaning, only the company that develop & produce it given the sole rights to manufacture and market it. After the period of patent ends, other companies can manufacture & sell drugs containing the same active ingredients. These products are called generic drugs  GENERIC DRUGS Generic name = non-proprietary name Often written without capital letter. eg ‘paracetamol’ Generic drug is same as innovator drugs in terms of : - Active ingredients that produce therapeutic effects - Effects: therapeutic and adverse effects - Dosage form (e.g. tablet, injection) - Clinical indications & strength - Safety How to show same effects as innovator: Bioequivalence studies  DRUG NOMENCLATURE Drugs often have 3 types of names: i) Chemical name: based on molecular structure of the drug ii) Generic or nonproprietary name iii) Trade name (brand name / proprietary name) E.g. paracetamol (generic name) huruf kecil N-(2,3,5,6-tetradeuterio-4-hydroxyphenyl)acetamide (chemical name) Panadol (trade/brand name) – huruf besar E.g. acetyl salicylic acid (chemical name) aspirin (nonproprietary name). Disprin (trade name / proprietary)  Examples CHEMICAL NAME ACTIVE INNOVATOR e.g. GENERIC BRAND INGREDIENT BRAND NAME NAMES ranitidine HCL Zantac X’tac piroxicam Feldene Apo-piroxicam mefenemic acid Ponstan Mefetab ethyl 4-(8-chloro-5,6-dihydro-11H- benzo[5,6]cyclohepta[1,2-b]pyridin-11- loratidine Clarityne Loratin (Cipla – India) ylidene)-1-piperidinecarboxylate. n-acetyl-para- paracetamol Panadol Uphamol, Partamol aminophenol Acetyl salicylic acid aspirin Disprin Aceprin (HOVID)  Some terms you may hear in pharmacology FDA: Food and Drug Administration (United States) OTC: over the counter drugs. Can be bought without doctor prescription as they have proven long term safety Prescription-only medicine; these drugs cannot be bought without a doctor’s prescription Drug formulary: A list of drugs, together with information on each drug. Can be national, or institutional (eg HUSM formulary) List of drugs approved for use in that country, or institution. Fake drugs / counterfeit drugs: drugs not registered with National Pharmaceutical regulatory agency (NPRA) of KKM. Fake drugs are not tested & illegal to be sold  FAKE / COUNTERFEIT DRUGS Not tested for safety Are there fake drugs in Malaysia? How do we know a drug is fake? Products registered with Ministry of Health (Malaysian MOH) will have registration number & hologram sticker at the product packaging How we knoe the hologram is authentic? - Pharmacists – meditag decoder - Meditag apps (by MOH) - Check registration status at NPRA (MOH) website Careful online drugs!  Drug sources Natural - Animal - Plants - Microorganism - Mineral Synthetic - Synthetic - Semi-synthetic Natural is safe? (curare – paralysis – death!)  Plant Source Drug Medical use Leaf of digitalis plant digoxin heart failure Bark of cinchona plant quinine malaria Fruit of opium morphine analgesic  Animal Source Drug Medical use Leech hirudin Anti-coagulant Pork pancreas (porcine) insulin diabetes Cow pancreas (bovine) insulin diabetes Animal thyroid Thyroid hormone Hormone  Microorganism e.g. bacteria, fungi Source Drug Medical use Penicilin notatum penicillin Antibiotics Streptomyces fradiae neomycin Antibiotics Mineral Ferrous sulphate anemia Aluminium hydroxide antacid Human source of drugs Via recombinant DNA technology E.g. regular insulin, tissue plasminogen activator (TPA) as thrombolytic First licensed drug produced using recombinant DNA technology was human insulin Synthetic drugs: Prepared in the laboratory Some drugs previously obtained from plant now prepared in lab Semi synthetic: Obtained by changing chemical structure of naturally obtained drug eg ampicillin ‘so many drugs, how to remember?’ Not possible to remember all. Fortunately, we can often arrange drugs into groups eg opioids (morphine, heroin) Drugs in each group often similar in actions, & sometimes pharmacokinetic profile too THERE YOU ARE …….THIS IS PHARMACOLOGY!!