Basic Principles of Pharmacology for GEMP Access Course PDF

BASIC PRINCIPLES OF PHARMACOLOGY FOR GEMP ACCESS COURSE  INTRODUCTION PROF. KWASI A. BUGYEI DEPT OF MEDICAL PHARMACOLOGY UNIVERSITY OF GHANA MEDICAL SCHOOL KORLE-BU, ACCRA  PHARMACOLOGY Pharmacology (Greek: pharmakos = a drug), logos = knowled...

BASIC PRINCIPLES OF PHARMACOLOGY FOR GEMP ACCESS COURSE  INTRODUCTION PROF. KWASI A. BUGYEI DEPT OF MEDICAL PHARMACOLOGY UNIVERSITY OF GHANA MEDICAL SCHOOL KORLE-BU, ACCRA  PHARMACOLOGY Pharmacology (Greek: pharmakos = a drug), logos = knowledge, discourse in All knowledge pertaining to drugs The science of the action of drugs on biological systems e.g. plants/animals/human beings, etc. 3  PHARMACOLOGY Defn: Study of interaction of living (biological) systems & molecules (chemicals) esp. xenobiotics endogenous Interaction mutual drug effect  body effect 4  PHARMACOLOGY Divisions of Pharmacology Pharmacokinetics Pharmacodynamics   Body handles drugs Drugs affect body   ADME factors Mechanism of action (Physiological/Biochemical) 5  PHARMACOLOGY Basic Principles 1. There is an active principle in any drug pharmacological effect (therapeutic/side/toxic effect) 2. Most drugs bind to receptors (many types) effect 3. There is a relationship between dose & effect (response) 4. Drugs of similar chemical structures (congeners) similar effect, but different potency 6  PHARMACOLOGY 5. Drug response vary from person to person 6. Group name & reason for its existence - Group name = antihypertensives - Reason = management of hypertension 7  THE DRUG DRUG = DROOG = DRY (Dutch) or DROGUE = DRY HERB (French) Originally drugs were made up of mainly dried plant parts or herbs Defn. Small chemical molecules when introduced into the body cause changes in physiological or biochemical processes. Have toxic effects on organisms that invade the body 8  THE DRUG Students should give examples of drugs based on the definition - - - 9  THE DRUG Conclusion Every thing is a drug What then is a poison? 10 SYMBOL OF POISON 11  The Drug cont’d The difference between drugs & poisons Drugs have safety dose range A poison - has little or no safety-dose range (small dose toxicosis (poisoning) 12  The Drug cont’d. When does a drug becomes a poison? Drugs are chemicals usually used within the therapeutic range A drug becomes toxic/poison only when; - an overdose is given - used for a long time - administered via the wrong route 13  Uses of Drugs Uses of Drugs Treatment (antibiotics) Diagnose (edrophonium) Prevent diseases (vaccines, antibiotics, pesticides etc) Socio-economic expediency (e.g. antifertility drugs for birth control) Recreational purpose (marijuana, alcohol etc.) 14  THE DRUG Medically, drugs are usually referred to Chemical substances used to: - Treat disease(s) - Prevent disease(s) - Diagnose diseases(s) 15  Sources of Drugs Many Sources of Drugs 1- Natural 2- Synthetic 3- Semisynthetic 4- Genetic engineered sources 5- Immunological sources *Most drugs are weak electrolytes* 16  Sources of Drugs cont’d. Natural Biological = animals, plants and microorganisms Animals - e.g. insulin, heparin Plants - e.g. morphine, reserpine, artemether Microorganism - e.g. antibiotics Non-biological = minerals Minerals - e.g. MgSO4, Ca(HCO3)2, liquid paraffin 17  The Drug cont’d. Synthetic Sources – drugs wholely manufactured E.g. various forms of chemotherapeutic agents - sulphonamides - procaine - corticosteroids - methotrexate 18  Sources of Drugs cont’d. Semisynthetic Sources - Produced by combining natural and synthetic products e.g. Co-amoxiclav (Augmentin) Clavulanic acid (synthetic) + amoxycillin ( natural = aminopenicillin) 19  Sources of Drugs cont’d. Genetic Engineered Drugs - Employs DNA recombinant technique e.g. insulin production, gene codes for insulin in humans are taken from the human genome and inserted into an animal genome - The animal will then produce human insulin which is harvested and used (Transgenic animals) 20  Sources of Drugs cont’d. Immunological sources Antigens → antibodies e.g. vaccines Antiserum/antivenins e.g. snake antivenoms 21  PHARMACOKINETICS The PK of a drug refers to the way the body handles drugs i.e. it involves ADME factors Absorption = movement of drug from site of administration into circulation Distribution = movement of drug from circulation to the tissues 22  PHARMACOKINETICS Metabolism = chemical conversion of the drug to more polar compounds Excretion = elimination of drug from the body via renal, biliary or other processes 23 24  DRUGS Formulation of Drugs (Drug dosage forms) Tablets Suspensions Oblets Solutions Capsules Syrups Caplets Liniment Pills Lotions Suppositories Gels Pessaries Bitters Creams 25  Factors Influencing Drug Absorption The routes of drug administration determine the site/surface area of absorption → extent of absorption of the drug into circulation 26  ROUTES OF DRUG ADMINISTRATION Routes of Drug Administration Enteral Parenteral Directly into GIT By-passing the GIT 27  Enteral Routes 6 Types of Enteral Routes Oral or per os (PO) Naso-gastric Oro-gastric Buccal Sublingual Rectal 28 Naso-gastric 29 Naso-gastric 30 31 32  Parenteral Routes Defn.: The GIT is by-passed Types of Parenteral Routes injection routes non-injection routes (invasive) (non-invasive) 33  Parenteral Routes Many Injection Routes - IV - Epidural - IM - Intraosseous - SC - Intra-arterial - Intraperitoneal??? - Intrasynovial - Intrathecal 34 Intrathecal 35  Parenteral Routes Non-injection routes Topical Transdermal Inhalational 36  Parenteral Routes Topical route mucosa skin Drugs administered per this route are usually designed for local effects 37  Parenteral Routes Drugs applied to: Skin/Dermal Mucosa - Naso-pharynx - Nasal - Oro-pharynx - Conjunctiva - Vagina - Urinary bladder - Urethra 38 TRANSDERMAL 39  DRUG DISTRIBUTION Defn. The transfer of drug from systemic circulation (plasma/blood circulation) to tissues. Tissues = various sites in the body - Site of action - Storage site - Organs for drug metabolism (biotransformation) - Organs/routes of drug elimination 40  Drug Distribution Types of Drug Tissues where drugs distribute 1. ** Plasma Protein Binding** 2. Cellular Reservoirs 3. Fat as Reservoir/Depot 4. The Bone/Teeth as reservoirs 41  Drug Distribution 4. ** Plasma protein binding** Plasma protein source of bound drugs in circulation Drugs bound to plasma protein is in dynamic ↔ with free drug as dictated by law of mass action Acidic drugs basically bind to plasma albumin, whereas basic drugs bind to α 1-acid glycoprotein 42  Drug Distribution Distribution to Placenta Earlier Believe: The placenta impermeable to drugs Modern Concept: The placenta does not effectively exclude drugs from the fetus Typical example: The “Thalidomide disaster” Thalidomide is a sedative/hypnotic used in the 1960s (in pregnant women as antiemetic) Later found to cause congenital abnormalities amelia and phocomelia in fetuses 43  DRUG BIOTRANSFORMATION (METABOLISM) Defn. Drug biotransformation refers to the biological transformation of drugs from less polar to more polar substances (metabolites) so as to enhance elimination 44  Drug Biotransformation Purpose The sole purpose of drug biotransformation is to convert drugs into more polar substances to enhance excretion/elimination ***Biotransformation ≠ detoxification*** 45  Drug Biotransformation Reason 1. Inert parent drugs can be converted to active drugs (Prodrugs) 2. Resultant metabolites can have either ↑ or ↓ biological activity (sometimes no activity) compared to the parent compound 3. A metabolite can have adverse or even toxicological effect compared to the parent drug 46  Drug Biotransformation Enzymes catalyze all biotransformation rxns Two types: Microsomal Enzymes Non-microsomal Drug Metabolizing Enzymes Rate of biotransformation rxns varies among individuals in a population (genetic polymorphism) 47  EXCRETION Drug Elimination Defn. The process by which drugs (parent compounds or metabolites) are transferred from the body to the external environment Polar drugs are excreted more efficiently by the excretory organs, except the lungs which excrete both polar and non-polar drugs efficiently 48  Excretion The Principal Excretory Organs/Glands Kidneys (most important) Liver Mammary glands (nursing mothers) Lungs (volatile agents) Intestinal tract Skin (sweat glands) Salivary glands Lacrimal glands 49  Excretion The Kidney The kidney receives about 25% of cardiac output The kidneys have structures (nephrons) that enhance their ability to function as excretory organ 50 51  Renal Excretion Polar drugs and metabolites are excreted in the urine Many drugs are also excreted virtually unchanged in urine 52  HEPATO-BILIARY EXCRETION OF DRUGS Mechanisms of Biliary Excretion Two Pathways 1. Drugs enter hepatocytes (by active transport or passive diffusion) and secreted unchanged → bile → GIT → feces 2. Drugs enter hepatocytes (by active transport or passive diffusion) undergo biotransformation → bile → GIT → feces Result → prolongation of drug effect in the body53  PULMONARY EXCRETION Important for volatile drugs (alcohols, anaesthetic agents) Lungs provide large surface area of excretion (main advantage) 54  OTHER ROUTES OF EXCRETION Milk (nursing mothers) → babies at risk Saliva Sweat Tears 55