GP 1: Introduction to Pharmacology Department of Pharmacology

Learning objectives & Learning outcomes: Lecture: Introduction to pharmacology Objectives: To briefly introduce history and definitions in Pharmacology To define some commonly used terms in Pharmacology. To list sources of drugs To explain drug nomenclature – generic vs. proprietary names, OTC drugs etc. Learning outcomes: the learner should be able to state briefly history and definitions in Pharmacology” list with suitable examples sources of drugs Understand drug nomenclature – Generic vs. proprietary, OTC drugs etc.

Drug Safety has always been a concern …. and should remain so ‘First do no harm … it is a good remedy sometimes to use nothing.’ (Hippocrates, 5 th Century BC) ‘All things are poisons and there is nothing that is harmless … the dose alone decides that something is a poison.’ (Paracelsus, 1500s) ‘Patients may recover in spite of drugs … or because of them.’ (Gaddum, 1959)

Introduction to Pharmacology Pharmacology - “The branch of medicine that deals with the actions, mechanism of action & uses of drugs”. Greek – Pharmakon = drug, logos = study Pharmacology is the study of drugs. Clinical Pharmacology is the study of drugs in man.

Drug : (Drogue – dry herb) Substance used for the diagnosis, prevention, relief or cure of diseases. WHO Definition Any substance used to modify or explore physiological systems or pathological states for the benefit of the patient / recipient (including prevention, maintenance, termination or promotion of pregnancy). Pharmacotherapeutics deals with the use of drugs in the diagnosis, prevention & treatment of diseases.

Pharmakokinetics: What the body does to the drug. The changes that occur in the drug during its sojourn through the body & includes absorption, distribution, metabolism & excretion (ADME). Pharmacodynamics: What the drug does to the body. Study of biochemical and physiological effects of drugs & their mechanism of action. Pharmacy: Science of compounding & dispensing of drugs.

Prescription: Written order by a physician to a pharmacist to supply drugs in a definite dosage form with a definite composition, instructions & precautions for its use. Compliance: The extent to which the patient follows the treatment instructions. Toxicology: Study of toxic effects, treatment of drug poisoning with specific antidotes wherever available. Adverse Drug Reactions (ADR): harmful effects of drugs.  The art of therapeutics is to treat with maximum benefit and minimum adverse effects.

SOURCES OF DRUG INFORMATION 1.Text books 2.Physician’s Desk reference (PDR) 2.Journals 3.Pharmacopeias: are books providing information on approved therapeutic agents on their source, chemistry, physical properties, tests for identity, purity, assay & storage. Formulae of approved preparations are given. British Pharmacopoeia, American Pharmacopoeia, British National Formulary (BNF) 4.MIMS (Malaysia Index of medical specialties) annual etc. yearly publication with full prescribing information. 5.Advertising: Brochures, "Package inserts“ etc. should be analysed critically.

Recommended reading Lippincott’s Illustrated Reviews - Pharmacology 3 rd edition Basic & Clinical Pharmacology by Bertram G. Katzung, 10 th Edition Clinical Pharmacology by P N Bennett & M J Brown Goodman & Gilman’s The Pharmacologic Basis of Therapeutics

Sources of Drugs Minerals: Lithium, Potassium Natural - –Animals - Hormones - Insulin Antisera –Plants - Papaver somniferum - Opium Atropa belladona - Atropine Digitalis lanata - Digoxin Erythroxylon cocoa - Cocaine –Microorganisms – Penicillin Streptomycin Opium Poppy: Source of Morphine, Codeine etc.

Sources of drugs (contd) Synthetic Pethidine – morphine like drug Amphetamine - CNS stimulant Paracetamol (Panadol) – antipyretic Semisynthetics Heroin from morphine Methyl atropine from atropine Recombinant DNA technology Insulin Growth hormone

Drug nomenclature Chemical name: describes the chemical nature of the drug. Not generally used. Eg. Acetyl salicylic acid Generic name (Non-proprietary name or official name): Given by a competent scientific body & is internationally recognised. A drug has one single generic name. Eg. Aspirin, Pethidine, Paracetamol Generic name is also used to indicate a group of drugs such as sulphonamides. Proprietary name (Brand or trade name): is the patented property of the drug manufacturer. A single drug may have several proprietary names. There are several manufacturers, and prices vary greatly. Eg. Aspirin – Ecosprin; ASA 50; Paraetamol – Panadol, Crocin

Prescription drugs: those restricted to sale by prescription only. Eg. Antibiotics, Antihypertensives etc. Over the counter drugs (OTC Drugs) (Non-prescription drugs): OTC drugs are those safe for use by public for a short period & directions for their safe use can be provided. Cough & cold remedies, analgesics (Aspirin, Paracetamol) etc. Often advertised on TV, in journals etc. Remember: OTC drugs also can produce toxic effects. Misuse should be avoided.

What the body does to the drug What the drug does to the body

Pharmacokinetics: Fate of the drug during its sojourn through the body i.e. what the body does to the drug. Absorption Distribution ADME Metabolism Excretion

Lecture 2 Routes of Administration & Absorption of drugs

Basic pharmacokinetics [Part 1] Objectives: To explain the routes of drug administration with their advantages and disadvantages To explain the process of absorption of drugs and bioavailability To explain the factors affecting absorption of drugs Learning outcomes – the learner should be able to Explain the routes of drug administration and pharmacokinetics To be able evaluate the advantages/disadvantages of each route of drug adminstration Explain the process of drug absorption and bioavailability List and briefly explain the factors affecting absorption of drugs

Routes of administration Enteral- oral, buccal, sublingual, rectal Parenteral (other than enteral) Injection -  Intra-dermal  Subcutaneous (s.c.)  Intramuscular (i.m.)  Intravenous (i.v.)  Intra-articular  Intraperitoneal (i.p.) etc Pulmonary - inhalation Topical application– Skin ointment Eye drops etc.

Absorption Drugs are absorbed through cell membranes either by active process or by passive diffusion. Liquids are absorbed faster than solids. Buccal & sublingual routes – absorption is faster & the drug bypasses liver. Oral absorption of drugs is slower & incomplete than when given by intravenous route. Intravenous route is preferred in emergencies due to fast action & 100% drug availability for action. Topically administered drugs may act locally or get absorbed & produce systemic action.

Protein binding & Distribution of drugs Drugs exist in plasma as free fraction & protein bound fraction. Protein bound fraction of a drug remains in blood as it does not cross cell membranes while free fraction enters tissues and produces action. Drugs which cross placenta can affect the fetus.

Biotransformation & Excretion Biotransformation (Metabolism) Liver is the major site of biotransformation Usually leads to formation of inactive metabolites. Sometimes a drug is metabolized to active or toxic metabolites. Excretion – Either as unchanged drug or as metabolites Kidney is the major organ of excretion Other routes: lungs, saliva, feces, milk etc.

Pharmacodynamics – Effect of drug on the body Concentration-effect part Study of biochemical & physiological effects of drugs & their mechanism of action (MOA). Pharmacodynamics is what the drug does to the body.  MOA  Therapeutic & toxic actions  Factors modifying drug action

Drug Action & Effect: combination of a drug with the cellular components (eg. Receptors, Enzymes etc.) resulting in some change in the biological functions. Eg. Acetylcholine & Atropine act on the muscarinic cholinergic receptor –Acetylcholine contracts the smooth muscle –Atropine relaxes the smooth muscle Drug action and effect are used interchangeably. Acting where?? - Site of action What effect?? – Change in function How?? – Mechanism of action – Molecular

The same drug can produce Action at many levels in the organism - Eg. Ibuprofen or Aspirin Systemic - ↓ pain & fever Tissue - ↓ inflammation Cellular - ↓ prostaglandin synthesis Molecular - inhibits cyclooxigenase enzyme COX

Objectives for self study Definitions - Pharmacology, Clinical Pharmacology, Drug Pharmaco-therapeutics, Chemotherapy, Pharmacy, Prescription, Toxicology, ADR, Placebo, Compliance. Sources of Drug information Sources of Drugs Drug nomenclature –generic vs proprietary names OTC drugs Routes of drug administration - briefly Pharmacokinetics – very briefly Pharmacodynamics – drug action, drug effect