Introduction to Pharmacology PDF

Introduction to Pharmacology Dr. Abubakar Kabiru B.Pharm, MSc, PhD American International University West Africa, The Gambia Department of Pharmacy Definitions Pharmacology: the study of the interaction of drugs with living organisms....

Introduction to Pharmacology Dr. Abubakar Kabiru B.Pharm, MSc, PhD American International University West Africa, The Gambia Department of Pharmacy Definitions Pharmacology: the study of the interaction of drugs with living organisms. It also includes history, source, physicochemical properties, dosage forms, methods of administration, absorption, distribution mechanism of action, biotransformation, excretion, clinical uses and adverse effects of drugs. Drugs: chemicals that alter the function of living organisms. Drugs are generally given for the diagnosis, prevention, control or cure of disease. Definitions Pharmacodynamics: the study of the biological and therapeutic effects of drugs (i.e, “what the drug does to the body”) Pharmacokinetics: study of the absorption, distribution metabolism and excretion (ADME) of drugs (“i.e what the body does to the drug”) Toxicology: the science of poisons. Many drugs in larger doses may act as poisons. Poisons are substances that cause harmful, dangerous or fatal symptoms in Sources of Drugs Minerals: Liquid paraffin, magnesium sulfate, magnesium trisilicate, kaolin, etc. Animals: Insulin, thyroid extract, heparin and antitoxin sera, etc. Plants: Morphine, digoxin, atropine, castor oil, etc. Synthetic source: Aspirin, sulphonamides, paracetamol, zidovudine, etc. Micro organisms: Penicillin, streptomycin and many other antibiotics. Genetic engineering: Human insulin, human growth hormone etc. Pharmacodynamics Involves how the drugs act on target cells to alter cellular function Receptor and non-receptor mechanisms Receptors are protein molecules present either on the cell surface or within the cell, e.g. adrenergic receptors , cholinoceptors, insulin receptors, etc. Most drugs act by interacting with a cellular component called a receptor. Some drugs act through simple physical or chemical reactions without interacting with any receptor. eg.(Anta- acid & Omeprazol) adrenegic receptors(adrenalin(fight&flight)) cholinoreceptors(actyl choline(rest&sleep)) insulin receptors(insulin(metabolism&energy regulation) Receptor and non-receptor mechanisms Endogenous neurotransmitters, hormones, autacoids and most drugs produce their effects by binding with their specific receptors Aluminum hydroxide and magnesium trisilicate, which are used in the treatment of peptic ulcer disease, act via non-receptor mechanisms by neutralizing the gastric acid (chemical reaction) Receptor and non-receptor mechanisms Many drugs are similar to or have similar chemical groups to the naturally occurring chemical and have the ability to bind onto a receptor where one of two things can happen - either the receptor will respond or it will be blocked. A drug, which is able to fit onto a receptor, is said to have affinity for that receptor. Efficacy is the ability of a drug to produce an effect at a receptor. An agonist has both an affinity and efficacy whereas antagonist has affinity but not efficacy or intrinsic activity. Agonist vs. Antagonist When a drug is able to stimulate a receptor and produce an effect, it is known as an agonist and therefore mimics the endogenous transmitter. When the drug blocks a receptor, it is known as an antagonist and therefore blocks the action of the endogenous transmitter (i.e. it will prevent the natural chemical from acting on the receptor). However, as most drug binding is reversible, there will be competition between the drug and the natural chemical to the receptor. Chemical Bonding The forces that attract the drug to its receptor are termed chemical bonds and they are: Hydrogen Ionic (between charged ions) Covalent Vander Waals Force (weakest) Covalent bond is the strongest bond and the drug-receptor complex is usually irreversible. Drug Receptor Complex When first messengers like neurotransmitters, hormones, autacoids and most other drugs bind with their specific receptors, the drug receptor complex is formed The drug receptor complex causes the synthesis and release of another intracellular molecule termed second messengers e.g. cyclic AMP, calcium, inositol triphosphate (IP3), etc. These second messengers produce the molecular mechanism of drug action Site of Drug Action A drug may act: 1. Extracellularly e.g: osmotic diuretics, plasma expanders 2. On the cell surface e.g.: digitalis, penicillin, catecholamines 3. Intracellularly e.g.: anti-cancer drugs, steroid hormones Dose Response Relationship The amount of drug administered will determine the kind of response you get Minimum dose: the smallest dose that can produce a therapeutic effect Maximum dose: the largest dose that can be safely administered Toxic dose: the amount of drug that can cause a harmful effect Lethal dose: the amount of drug that can cause death Therapeutic Index The ratio of the dose that produces the desired therapeutic effect (effective dose) to the dose that produces a toxic effect (toxic dose) Safer drugs have wider therapeutic windows (penicillin); drugs that require more frequent monitoring have narrow therapeutic windows (digoxin, warfarin) Pharmacokinetics Deals with the absorption, distribution, metabolism and excretion drugs in the body. “What the body does to the drug” Absorption The process by which a drug enters into the systemic circulation from the site of administration through a biological barrier In the case of intravenous or intra-arterial administration, the drug bypasses rigorous absorption processes and enters into the circulation directly Routes of administration: alimentary tract (enteral) and parenteral Alimentary Tract 1. Buccal cavity: e.g. ondansetron ODT 2. Sublingual: e.g. nitrates 3. Oral: e.g. aspirin, alcohol 4. Rectum: e.g. PCM rectal suppositories, enemas Enteral Routes ADVANTAGES DISADVANTAGES Safe Slow onset of action Convenient Irritant drugs cannot be Economical administered this way Not useful in vomiting and severe diarrhea Gastric acid and digestive enzymes may destroy some drugs Parenteral Routes 1. Intradermal: layers of the skin, e.g. B.C.G. vaccine 2. Subcutaneous: Non-irritant, into subcutaneous tissue, e.g. insulin 3. Intramuscular: Soluble substances, mild irritants, suspensions and colloids can be injected by this route. These injections can be given to deltoid or gluteal muscle 4. Intravenous: into veins 5. Intrathecal: subarachnoid space of spinal cord, e.g. anesthesia 6. Intraarticular: into joints, e.g. hydrocortisone B.C.G. Vaccine- Bacillus calmette- Guerin is a vaccine primarily used to protect aganist tuberculosis. Parenteral Routes ADVANTAGES DISADVANTAGES Fast onset of action Pain at injection site Uniform rate of absorption Drug effect cannot be Can be given in critical halted immediately condition Trained professionals have Can be given in large to administer volumes Topical/Local Route Application of a drug directly to the surface of the skin Doesn’t reach systemic circulation in large quantities Includes administration of drugs to any mucous membrane Eye, nose, ears, vagina Dusting powder, paste, lotion, drops, ointment, suppository for vagina, patches Topical Route ADVANTAGES DISADVANTAGES Useful for the local delivery Not absorbed via skin or of agents, especially those mucous membranes which have toxic effects if Possibility of local skin administered irritation systematically Contact dermatitis likely Convenient to use and easy to apply due to excipients Avoidance of first pass metabolism Inhalation Route Used for gaseous and volatile agents and aerosols Solids and liquids are excluded if particle size is larger than 20 microns Administered as dry powders, and nebulized particles when sprayed as fine droplets get deposited over the mucous membrane producing local effects and may be absorbed for systemic effects Salbutamol inhaler used in bronchial asthma and volatile general anesthetics Inhalation Route ADVANTAGES DISADVANTAGES Fewer systemic side Patient may have difficulty effects administering/measuring Effective for patients with dose respiratory problems Some require assembly Rapid onset of action May cause irritation Bioavailability The rate and amount of drug that reaches the systemic circulation and is available at the site of action after nonvascular administration When the drug is given IV, the bioavailability is 100% The route of administration determines the period between administration and onset of action Bioavailability Drugs given by mouth may be inactive for the following reasons: 1. Enzymatic degradation 2. Poor absorption through gastrointestinal tract e.g. aminoglycosides 3. Inactivation by liver e.g. during first passage through the liver before it reaches systemic circulation First Pass Metabolis m Drugs that are absorbed via the GIT are circulated to the liver first Liver acts as a filter Only part of the drug enters systematic circulation Factors affecting absorption Physio-chemical properties of drug Gas > Liquid > Solid Lipid Soluble > Water Soluble (Unionized > Ionized) Nature of the dosage form Small particles > Big particles Pharmacogenetic factors Disease states Factors affecting absorption Physiological factors 1. Administration without, with, or after food 2. Presence of other agents (vit C w/ iron vs. tetracyclines w/ antacids) 3. First pass effect 4. Surface area (vasculature): small intestine > stomach Distribution Penetration of a drug to the sites of action through the walls of blood vessels from the administered site after absorption Drugs distribute through various body fluid compartments such as: (a) plasma (b) interstitial fluid compartment (c) trans-cellular compartment Factors affecting distribution Protein binding Protein bound vs free drug Plasma concentration IV, falls sharply Oral, rises and falls gradually Sublingual, rises sharply and falls gradually Clearance Physiological barriers Blood brain barrier (BBB) Placenta Plasma Concentration Graph Metabolism Drugs are chemical substances, which interact with living organisms and produce some pharmacological effects After, they should be eliminated from the body unchanged or changed to some easily excretable molecule The chemical reactions involved in biotransformation are classified as Phase 1 and Phase 2 reactions Phase 1 Reactions Make the drug polar (water soluble) so it can be excreted via urine Oxidation Reduction Hydrolysis Typically involves the use of cytochrome P450 enzymes Phase 2 Reactions Some drugs may not be excretable after Phase 1 and will need to undergo further metabolism Combines an endogenous substance with the drug (conjugation) Glucuronidation Methylation Acetylation Sulfation Excretion The transportation of unaltered or altered form of drug out of the body. Major processes of excretion include renal excretion, hepatobiliary excretion and pulmonary excretion Minor routes of excretion are saliva, sweat, tears, breast milk, vaginal fluid, nails and hair Excretion