Monash University Introduction to Pharmacology PDF

Introduction to pharmacology [email protected] Warning: This material has been reproduced and communicated to you by or on behalf of Monash University under Part VB of the Copyright Act 1968 (the Act). The material in this communication may be subject to copyright under the Act. Any furt...

Introduction to pharmacology [email protected] Warning: This material has been reproduced and communicated to you by or on behalf of Monash University under Part VB of the Copyright Act 1968 (the Act). The material in this communication may be subject to copyright under the Act. Any further reproduction or communication of this material by you may be the subject of copyright protection under the Act. Do not remove this notice. Unless otherwise indicated, all images are the property of Pearson Education Limited.  Unless otherwise stated, all images are the property of Pearson Education Limited: Marieb & Hoehn, Human Anatomy & Physiology, 10th ed., 2016 Martini, Nath & Bartholomew, Fundamentals of Anatomy & Physiology, 2012 2  Learning objectives 1. Briefly describe drug sources and how drugs are named. 2. List the various drug administration routes and describe advantages and disadvantages for the various routes. 3. Describe pharmacokinetics, including absorption, distribution, metabolism, excretion, first-pass metabolism and bioavailability. 4. Describe what is meant by therapeutic range and half life of a drug and why these factors are important in a drug dosage regime. 5. Describe pharmacodynamics and list the 4 protein targets (carrier proteins, enzymes, ion channels and receptors) of drugs. 6. Briefly outline what is meant by adverse drug reactions, hypersensitivity, drug interactions, contraindications and drug transfer. 3  Pharmacology is the study of chemicals(drugs) affecting body functioning. The World Health Organization defines a drug Introduction as: to “any substance or product that is used or intended to be pharmacology used to modify or explore physiological systems or pathological states for the benefit of the recipient” Pharmacology includes: Pharmacodynamics the drugs effect on the body Pharmacokinetics the bodies effect on the drug 4  Sources and names of drugs Learning Objective 1: Briefly describe the various sources of drugs and how drugs are named Drugs are derived from a variety of sources: Microorganisms Plants Animals Minerals Synthesised in laboratories Fungus on this lemon Purified penicillin (white) may include inhibiting bacterial growth (blue) penicillium mould Example: The antibiotic penicillin is produced by a fungus 5 http://champignons.moselle.free.fr/cha/penicillium_digitatum_1.htm http://www.skylinecollege.edu/case/antibiotics.html  Sources of drugs: Plants Plants and plant parts have been used as medicine for centuries and remain an important source of chemicals used for developing into drugs today. Morphine - derived from the poppy plant Papaver somniferum →used for pain management Digoxin – derived from Digitalis purpurea plant (purple foxglove) →used to slow heart rate and treat congestive heart failure Caffeine – derived from the Caffea arabica plant Papaver somniferum Caffea arabica (morphine) Digitalis purpurea (digoxin) (caffeine) http://galleryhip.com/papaver-somniferum.html 6 http://commons.wikimedia.org/wiki/File:Digitalis_Purpurea.jpg http://citytouraroundbogota.blogspot.com.au/2011/05/coffe.html  Sources of drugs: Animals § Animal products have been used to replace human chemicals affected by disease or genetic problems. Adrenaline - originally obtained from the adrenal glands of monkeys, sheep and cows, now synthesised artificially →used to treat anaphylaxis, cardiac arrest Insulin - originally isolated from pigs and cows, now synthesised artificially by genetically modified bacteria →used to treat diabetes 7 http://australianpork.com.au/wp-content/uploads/2013/09/home-slide-01.jpg  Drug names (Drug nomenclature) Drugs have several names § The chemical name is a description of the chemical composition of the drug and identifies the drugs atomic and molecular structure, e.g. para-acetyl-amino-phenol C8H9NO2 § The generic (non-proprietary) is the abbreviated and approved name given to a drug by the manufacturer to first develop it, e.g. Paracetamol. A generic name set by the Therapeutic Goods Administration (TGA) for use in Australia is An Australian Approved Name (AAN) § The trade (proprietary) or brand name is selected by the drug company selling the drug. Protected by a trademark. So the same drug can have several trade names when produced by a number of different manufacturers, e.g. Panadol, Panamax, Dymadon and Tylenol. 8  Routes of administration Learning objective 2: List the various drug administration routes and describe advantages and disadvantages for the various routes § Route of administration How the drug is introduced into the body Determines how well it is absorbed and how easily it reaches its target →determines the effectiveness of the drug § Choice of route of administration governed by physical and chemical properties of the drug (e.g. solid, liquid, gas, pH at site of action) plus patient factors (e.g. conscious state) 9 http://www.italnastri.it/images/testate/Testata_settori-merceologici_prodotti-farmaceutici.png  The enteral (oral) route Medications absorbed via the gastrointestinal (GIT or enteral) system. The oral route suggests that, in most instances, the person will swallow the drug before it reaches the gastrointestinal tract but also includes drug administration: § through a nasogastric tube § via PEG, gastronomy or other enteral feeding device Medications administered by the enteral/oral route are subject to first pass metabolism (more on this later) http://www.ktpadvisors.com/wp-content/uploads/2012/12/specialty-drug.jpg https://d2k76y8sp2npyk.cloudfront.net/images/content/6eec334e-23fe-4b90-adee- 10 f7025b7ebd3d/be236f5a-aed3-4875-97c7-00cd157a37e1_Enteral_Feeding_Formulas.jpg  The enteral (oral) route Most commonly used route of administration § Drugs administered via the enteral route can take many forms: Tablets Capsules Lozenges Liquid preparations § Advantages Easily administered Pain free Non invasive Economical Normally good absorption along whole length of GI tract Gradual increase in plasma concentration of drug https://www.healthnews.com.tw/upload/1414405665514020192.jpg 11 https://encrypted-tbn0.gstatic.com/images?q=tbn:ANd9GcR7ayYXbvBaFpntQYqgrN8cEIVwgdmKQSvv03-z9gHeE5SwbYfmHw  The enteral (oral) route § Disadvantages Requires patient compliance, i.e. to take the right dose at the right time Patient must be conscious and co-operative in order to be given the dose (except where administration is through an enteral tube) The medication may cause gastrointestinal irritation Medication effectiveness may be altered by food, gastric secretions, emotional stress or physical activity The drug may be denatured in the digestive tract, e.g. proteins such as insulin cannot be administered orally It takes longer for the drug to take effect The drug will be subject to first-pass metabolism (discussed later) 12  Sublingual and Buccal § Sublingual administration-drug placed under tongue to dissolve(disperse) § Buccal administration-drug placed between cheek and gum § Both routes facilitate rapid absorption of medication via the capillaries of the mucous membrane rather than being processed by the gastrointestinal system § Both avoid first pass metabolism http://nursingcrib.com/wp-content/uploads/2009/07/routes- https://dailymed.nlm.nih.gov/dailymed/archives/image.cfm? of-drug-administration.jpg archiveid=10744&type=img&name=Fentora-11.jpg 13  The parenteral route Any method of drug administration that avoids the gastrointestinal tract § Often refers to where an invasive procedure is used; primarily injecting directly into the body § Most common parenteral routes include intravenous (IV), intramuscular (IM) and subcutaneous (SC) § Includes intra-arterial and epidural (drug injected into spinal canal outside duramater) Also includes drug injected directly into other body cavities https://img.aws.livestrongcdn.com/ls-article-image- 400/getty/xc/83290868.jpg?v=1&c=EWSAsset&k=2&d=F 1683185B4CC780928E7827F8F6FE8B1C5BFAB757CF26D8 1F32AE2F4EF8A8271 https://dtc.ucsf.edu/wp-content/uploads/2010/09/dtc_000015308899.jpg https://pocketdentistry.com/wp-content/uploads/285/B9780323056809000266_gr1.jpg 14  The parenteral route § Advantages Provides an alternative when drugs given orally are poorly absorbed, inactive or ineffective. The IV and intra-arterial routes provide immediate onset of action. The IM and SC routes can be used to achieve a slower or delayed onset of action. Problems with patient co-operation, compliance and conscious state can be avoided. Avoids first pass metabolism. (more on first pass metabolism soon) 15 https://upload.wikimedia.org/wikipedia/commons/thumb/0/0d/ICU_IV_1.jpg/1200px-ICU_IV_1.jpg  The parenteral route § Disadvantages Skill required to inject correct site using the required technique Aseptic technique required to avoid the risk of infection The onset of drug action can be rapid Requires accurate dosage It can be painful It is often more expensive May require additional equipment (e.g. I.V. cannula and tubing, plus programmable infusion pump) 16 http://www.treatcancer.com/wp-content/uploads/2014/05/photodune-6691589- iv-drip-attached-to-patients-hand-during-chemotherapy-m-710x270.jpg  Other routes of administration (Parenteral) § Inhalation (pulmonary route) - Drugs administered by gas or fine mist. The lungs provide a large surface area for absorption. Respiratory membrane and its rich capillary network allows drugs to readily enter the circulation. Examples include anaesthetic agents and bronchodilators administered by nebulisers or “puffers”. § Topical route – applying drug to the skin or mucous membranes. Used to produce local or systemic effects. Includes administration via skin, eyes, ears, nose, vagina and rectum. Medication may take the form of an ointment, transdermal patch, drops, pessaries or suppositories. Must be applied to intact skin. 17 http://molochnitsa.com/wp-content/uploads/2016/04/rektalnye-730x425.jpg Some Examples of parenteral and enteral medication Enteral Route Site of administration Example Oral Digestive tract via mouth Paracetamol tablet Gastric Digestive tract via nasogastric tube Paracetamol in suspension Duodenal Digestive tract via feeding tube Paracetamol in suspension Parenteral Route Site of administration Example Subcutaneous (SC) Injection into subcutaneous tissue Local anaesthetic agents, (under the epidermis) insulin Intramuscular Injection into muscle tissue Vaccinations Intravenous Injection into vein Antibiotics, resuscitation fluids e.g. saline, dextrose (intra-)Arterial route Injection into artery Chemotherapy, adrenaline Epidural Injection into epidural space Anaesthetic agents Intrathecal Injection into subarachnoid space Spinal anaesthetics Not a comprehensive list Intranasal Nasal cavity Decongestant (anti-inflammatory) drops or aerosol sprays Sublingual Mucosa under tongue Glyceryl trinitrate (GTN) tablet Topical (cutaneous) Epidermis of the skin Creams, lotions Transdermal Dermis of skin Glycerin trinitrate (GTN) patches Inhalation Respiratory membrane of lungs Ventolin-nebulized fine mist  Pharmacokinetics Learning objective 3: ADME Describe pharmacokinetics, including absorption, distribution, metabolism, excretion, first-pass metabolism, bioavailability http://biology-forums.com/gallery/46687_12_12_14_7_07_20_19543396.jpeg  Pharmacokinetics The study of how the body effects the drug is called pharmacokinetics § Once a drug has been administered into the body, the drug must reach its molecular target § The amount of drug that interacts with its target is influenced by how the drug is: Absorbed into the body Distributed around the body Metabolised by the body Absorption Excreted from the body Distribution Metabolism Excretion 20  Pharmacokinetics: Absorption Movement of drug from the site of administration to the systemic circulation. Before a drug gains access to internal compartments of the body absorption must take place. Most drugs are subject to absorption. Exceptions include some of the parenteral injections § Intravascular administration means a drug will directly enter the systemic circulation, bypassing the many complications of absorption from other routes. § Intravascular administration includes the intravenous and intra-arterial routes. § These parenteral routes of administration effectively bypass absorption. Drugs administered in this way immediately commence being distributed around the body. https://i.pinimg.com/564x/fc/0b/b9/fc0bb92fa3bc4e58fc9266b782352913--capsule-action.jpg 21  Pharmacokinetics: Absorption Movement of drug from the site of administration to the systemic circulation. § Many drugs are introduced into the body from outside the blood stream, e.g. topical, oral, subcutaneous, and must first be absorbed before having any effect. In the case of medication(tablet) taken orally → disintegrated (broken down) → goes into solution (dissolution) → is absorbed from the small intestine → into the hepatic portal system (blood supplygliver) Hepatic portal vein → then into systemic circulation Liver Systemic circulation HEPATIC PORTAL SYSTEM DISCUSSED AS PART OF THE DIGESTIVE SYSTEM BE SURE TO REVIEW THIS IMPORTANT CIRCULATION NETWORK 22 https://i.pinimg.com/564x/fc/0b/b9/fc0bb92fa3bc4e58fc9266b782352913--capsule-action.jpg  Factors affecting drug absorption § The formulation of a drug, i.e. oral route - a liquid medication is more rapidly absorbed than a tablet § The route of administration § Tissue surface area and thickness absorption through the small intestine (large surface area and single layer of epithelial cells) is quicker than through the local topical administration on skin (small surface area, multiple cell layers to cross) § The blood supply at the site of administration Highly vascularised area (e.g. the sublingual route) →more rapid absorption vs. poorly vascularised area (e.g. subcutaneous injection) → slower absorption Patients with cardiovascular disease may have reduced blood circulation → slows absorption rate 23  Factors affecting drug absorption The solubility of a drug For absorption to occur, a drug must be in solution, able to cross the plasma membrane (e.g. of intestinal epithelial cells, epithelial cells of skin) and enter blood capillaries lipid-soluble drugs → easily cross the plasma membrane via simple diffusion → rapid absorption water-soluble drugs → cross the plasma membrane via facilitated diffusion or active transport → slower absorption Lipid-soluble drugs Water soluble drugs Small water-insoluble drugs Extracellular fluid Cell membrane Intracellular fluid 24 Marieb & Hoehn, fig 3.7  Pharmacokinetics: Distribution Distribution is the process of reversible transfer of a drug between one location and another in the body Once the drug has reached the systemic circulation it can be distributed to various body compartments including § fluid compartments gin particular blood § intracellular compartments gtarget tissue plus other tissue e.g bone & fat Depending on the type of drug, the drug may: § be distributed to organs that are well perfused (i.e. good blood supply) § be distributed more slowly to areas that are poorly perfused (e.g. adipose tissue) § remain in the blood 25  Factors affecting drug distribution Distribution The movement of a drug to body tissues. Depends on: § Drug solubility (water or lipid soluble) § Cardiovascular functioning (especially cardiac output) § Perfusion of the area Degree of blood flow (vascularisation) The permeability of the capillaries, i.e. brain vs. liver § pH of the area § Binding of drug to plasma proteins. Upon entering the systemic circulation: a proportion of drug molecules bind reversibly to plasma proteins a proportion of drug molecules remain “free” or unbound pharmacological action is exerted by unbound drug, so a high degree of plasma protein binding will affect drug efficacy. Once “free” drug is removed from circulation (e.g. via metabolism, excretion) more protein bound drug will be released. 26  Factors affecting drug distribution The movement of a drug to body tissues. Depends on: § Tissue binding. Adipose tissue. Lipid soluble drugs have a high affinity for adipose tissue. Low blood flow to this tissue means some drugs may be stored here. Bone tissue. Some drugs have a special affinity for bone and can accumulate here. This decreases immediate distribution. Drugs having accumulated here may be released slowly over time. http://www.sciencemag.org/sites/default/files/styles/inline__699w__ 27 https://img.aws.livestrongcdn.com/ls-article-image-673/ds-photo/getty/article/225/48/177559095.jpg no_aspect/public/SciSource_SS4631_16x9.jpg?itok=LzL8sTDp  Barriers to drug distribution Blood-brain barrier. Made up of endothelial cells with tight intercellular junctions to protect CNS from potentially damaging microorganisms and other substances. Placental barrier. Membranes and enzymes providing incomplete protection to fetal circulation. http://www.macmillanhighered.com/BrainHoney/Resource/6716/digital_first_ content/trunk/test/hillis2e/asset/img_ch38/c38_fig19.jpg  Pharmacokinetics: Metabolism § Metabolism, or biotransformation, is the process where drugs are broken down into substances more easily excreted. These chemicals are termed metabolites. § The liver is the most important site of drug metabolism. Is facilitated by enzymes located here. § Rate of metabolism varies markedly between individuals. § Factors affecting metabolism include: § Genetics § Environmental factors These factors can Other medications, diet, alcohol, activity. all influence the § Age and gender bioavailability of a Infants have immature liver function The elderly show delayed metabolism of drugs drug (discussed Pregnancy can alter drug metabolism next slide) § Disease states The presence of hepatic, renal or cardiovascular disease will slow metabolism 29  Pharmacokinetics: Bioavailability Refers to the amount of drug that is available to exert a pharmacological effect. § Is the proportion (%) of the administered drug that reaches the systemic circulation. § Bioavailability varies with route of administration § Drugs administered orally undergo first-pass metabolism → bioavailability much lower than originally administered drug dose. § Drugs administered intravascularly do not undergo first- pass metabolism → bioavailability is 100% of originally administered dose of medication. Hepatic first-pass metabolism means, therefore, that the oral dose of a medication is often higher than would be given intravascularly. 30  Pharmacokinetics: Hepatic first pass metabolism § Applies to enteral administration of a medication § Medication enters stomach (if swallowed) or small intestine (via enteral feeding device) § Some medications will require further breakdown before being absorbed by GIT mucosa into blood of surrounding capillaries § Absorbed drug makes it way from capillaries into the hepatic portal vein for transport to the liver. § Some drug may be lost if not absorbed from the gastrointestinal tract. Removed with faeces. § Drugs reaching the liver undergo metabolism before reaching the systemic circulation. This is called first-pass metabolism.  Pharmacokinetics: Hepatic first pass metabolism A patient takes a 100mg dose of a drug, for example. Hepatic 80 mg of the dose is absorbed from the small intestine and reaches the liver via the hepatic portal vein → 20 mg was not absorbed from the small intestine The liver then metabolises the remaining 80 mg → 60 mg is irreversibly lost Metabolised (eliminated) (eliminated) Only 20 % of the original dose reaches the systemic circulation These proportions used to illustrate this scenario are This proportion that reaches systemic an example only and are not typical of every case. circulation is the remaining amount of drug available to exert a pharmacological effect – known as the BIOAVAILABILITY of the drug  Pharmacokinetics: Excretion The pharmacological effects of a drug continues until it is removed from the body. Elimination is the irreversible loss of the drug from the plasma. Occurs via metabolism and excretion. § Liver is the main site of elimination due to metabolism. Excretion is the irreversible loss of the drug from the body § Kidneys excrete most drugs and their metabolites § Drugs can be eliminated in bile so removed from the body in faeces § Lungs the primary route for excretion for volatile substances such as inhalation anaesthetics § Other routes include intestine, salivary, sweat and mammary glands 33  Pharmacokinetics: Excretion The kidneys are the primary site of drug excretion from the body. § Free unbound drug can be filtered from the blood into the renal filtrate § Lipid soluble drugs may be reabsorbed from the renal filtrate back into systemic circulation § Water-soluble drugs can also be secreted from the blood into the filtrate. The process of excretion is dependent on: urinary pH which can range from 4.6 – 8.2 renal and cardiovascular function. 34 https://www.brussels.be/sites/default/files/styles/article_image__hd_/public/mannekenpis.jpg?itok=OBJ21cra  Pharmacokinetics: Summary Pharmacokinetics-how the body affects the drug Absorption takes place at stomach & small intestine after enteral administration. No absorption required for vascular administration. Distribution around the body by systemic circulation. Metabolism and elimination by the liver. Excretion primarily by kidneys (some from lungs, in bile and others) The amount of drug that is available to exert a therapeutic or pharmacological effect after interactions with the body is known as the drugs bioavailability. 35  Rational drug use: developing a drug dosage regime Learning objective 4: Describe what is meant by the therapeutic range and half life of a drug and why these factors are important in a dosage regime Therapeutic range The range of concentration of a drug having a high probability of producing the desired therapeutic effect and low probability of toxic effects. § Achieved by a drug dosage regime which includes o the amount of drug administered and o how often the drug is administered § Derived from information about populations of individuals and pharmacokinetic profile of the drug. § Important to remember not everyone responds to the same drug in the same way. 36  Rational drug use: developing a drug dosage regime The therapeutic range lies between 2 concentrations: 1. The minimum effective concentration Minimum amount of drug required to cause a pharmacological effect 2. The minimum toxic concentration Minimum amount of drug that causes a toxic effect The therapeutic range of a drug depends on the route of administration, the pharmacokinetics of the drug and the characteristics of an individual § Characteristics of an individual to consider Age Gender Health/disease status Cardiovascular, liver and kidney function 37  Rational drug use: developing a drug dosage regime Drug half-life § The term half-life (T1⁄2) is defined as the time taken for the drug concentration to be reduced by 50% from its maximum concentration § The drug half-life tells us: How quickly a drug is being eliminated from the plasma How often we need to administer a drug to keep it within the therapeutic range § e.g. IV administration of 100 mg of a drug that has a half life of 4 h: Ø After 4 h, 50 mg will remain in plasma Ø After another 4 h (or 8 h in total), 25 mg will remain... Ø The drug should be administered at regular time intervals to keep the plasma concentration within the therapeutic range 38  Rational drug use: developing a drug dosage regime Minimum toxic concentration Cmax Value of Cmax Therapeutic range ½ Cmax Minimum effective Duration of action concentration T1/2 Onset of action Tmax Termination of action Notes on slide to follow 39  Rational drug use: developing a drug dosage regime § Minimum effective concentration- when there is enough drug in the plasma to begin exerting a pharmacological or therapeutic effect (example seen on previous slide shows 6mg/L) § Onset of action- time at which minimum effective concentration is reached (example seen on previous slide shows 2hrs) § Termination of action- concentration of drug has dropped below minimum effective concentration. No longer has a therapeutic effect (8hrs) § Duration of action- time between minimum effective concentration and termination of action. (6hrs) § Cmax- maximum plasma concentration of drug (≃ 16mg/L) § Tmax- time taken to reach maximum concentration of drug (time at which Cmax happens) (5hrs) § T1/2 - time taken for drug concentration to be reduced by half ➤ 50% of maximum concentration 40  Pharmacodynamics Learning objective 5: Describe pharmacodynamics and list the 4 protein targets (carrier proteins, enzymes, ion channels and receptors) of drugs § The study of how the drug effects the body is called pharmacodynamics and involves: The effect of the drug on the body The mode of drug action § The mode of drug action depends on the drug’s molecular target: Proteins (primary target) carrier proteins ion channels enzymes/chemical reactions receptors DNA, i.e. chemotherapy drugs 41 https://mhcbiofeedback.files.wordpress.com/2015/01/target.jpg  Pharmacodynamics: Carrier proteins § Drugs can alter the function of carrier proteins involved in facilitated diffusion and/or active transport § Drugs bind to and prevent the carrier protein from moving molecules into the cell e.g. some antidepressants block the re-uptake of the “feel-good” neurotransmitter NA in synapses g keeping NA in the synapse and thus enhancing its effects 42 M & H Fig 11.3  Pharmacodynamics: Ion channels § Drugs can alter the function of proteins involved in facilitated diffusion § Drugs act on ion channels by: Binding to the channel (or its associated receptors), causing the channel to open or close Blocking the channel 43 http://www.mdpi.com/2072-6651/2/10/2359/htm  Pharmacodynamics: Enzymes § Enzymes are biological catalysts that increase the rate of chemical reactions § Two main types of drugs affect enzymes: § Competitive inhibitors Drug binds to the enzyme active site ➤substrate cannot bind Slows or inhibits enzyme activity e.g. non-steroidal anti- inflammatory drugs (NSAIDS), Viagra, Strychnine. § Non-competitive inhibitors Drug binds to the enzyme, changing its shape ➤prevents substrate from binding The enzyme is destroyed e.g. Penicllin (acts on peptidogylcan wall in bacterial cells), Cyanide (toxic to humans) 44 http://www.buzzle.com/img/articleImages/609998-4049-47.jpg  Pharmacodynamics: Receptors § Receptors are: present on the cell membrane and within the cytoplasm involved in signaling between and within cells a major drug target § Drugs that bind receptors: Bind in place of the natural ligand Act as either an: Agonist - initiates or enhances the normal response Antagonist - blocks the normal response http://s2.thingpic.com/images/rQ/NR1AbSWv7ZA2fz6ZcaXSU2mc.jpeg 45  Pharmacodynamics: Various drugs will bind cholinergic or adrenergic receptors and effect ANS function e.g. drugs that affect sympathetic functions... Adrenergic Receptor Normal Typical agonist Typical Example receptors location response to drug anatognist binding of NA drug (natural ligand) β1 receptors Cardiac Increased Dobutamine Beta blockers, muscle cardiac activity e.g. and blood Propranolol or pressure timolol β2 receptors Smooth Dilation of Salbutamol Beta blockers, muscle in airways to (asthma e.g. airways and increase puffers) Propranolol blood vessels airflow and in heart and blood vessels skeletal to increase muscles blood 46 flow  Medication problems Learning objective 6. Briefly outline what is meant by adverse drug reactions, hypersensitivity, drug interactions, contraindications and drug transfer. https://encrypted- tbn0.gstatic.com/images?q=tbn:ANd9GcTl_PxAYXM0gmR Dl32e6CARNCJuXWqKHq-KvBTV7rQugnqHZo3f https://antioligarch.files.wordpress.com/2012/05/drugs-kill-you.png 47  Hypersensitivity § Substances foreign to the body act as antigens and can stimulate the bodies immune system. § The body’s immune system showing an exaggerated response to a drug perceived as a foreign substance is known as drug hypersensitivity i.e. an allergic reaction § The most dramatic form is anaphylaxis where sudden onset of bronchospasm, vasospasm and severe hypotension can rapidly lead to death. Rare. § Some involve altered reactions to medications. § Rashes commonly seen. 48 https://meded.ucsd.edu/clinicalimg/drug_skin3.jpg  Adverse drug reaction (ADR) § An unintended and/or undesirable effect of a drug Many drugs will cause some adverse effect in patients Includes drug hypersensitivity Requires alteration of the dosage regime or withdrawal of the medication § Consequences: Decreased effectiveness of treatment Poor therapeutic outcomes Ø Prolonged illness Ø Increased length of hospital stay Ø Increased costs Ø Higher mortality rates 49 https://image.slidesharecdn.com/vernon-140122151850-phpapp01/95/the-pieces-of-the-puzzle-in- optimizing-medications-polypharmacy-in-the-elderly-9-638.jpg?cb=1390410585  Adverse drug reaction (ADR) § Predisposing factors for ADR: Age – elderly and neonates Twice as common and more severe in elderly Gender – more common in females (size?) Dose – many are dose related Polypharmacy (taking multiple, different medications) – increases risk, especially in elderly History – frequent presenter/chronic condition at higher risk Genetic factors – possible liver enzyme deficiency 50 http://netdoctor.cdnds.net/15/51/1600x800/landscape- 1450186023-g-different-medicines-171626219.jpg  Drug interactions § A drug-drug interaction (DDI) occurs when the pharmacological effect of one drug is altered by another drug The effect could be an enhanced therapeutic effect of the drug, or A decreased therapeutic effect of the drug, or An ADR § May occur for both prescription and non- prescription medications § DDI occur frequently and result in a significant number of hospital admissions 51 https://static.diabetesaustralia.com.au/s/images/diabetes- australia/332cc965-7d7b-457b-b1cb-7f5b913ef3f9.jpg?w=1200  Drug contraindications Contraindication - a factor that makes the administration of a drug undesirable or even dangerous. Factors may include: § patient statis Premature infants, neonates and the elderly - liver and kidney function may be inefficient Pregnant women - medications that can cross the placenta and effect the growing fetus § a current disease state Kidney disease - clearance (excretion) will be reduced Liver disease - metabolism and clearance (elimination) will both be affected § drug therapy with potential for interaction or adverse reaction Digoxin and Amiodarone Digoxin in bradycardia These conditions determine when a drug should NOT be prescribed 52  Drug transfer Any drug given to a pregnant woman may reach the growing fetus via the circulation or be transferred to a neonate via breast milk during feeding e.g. codeine, aspirin, antibiotics, caffeine § Factors contributing to potential harm: Drug properties and dosage Gestational age of the fetus 1st trimester – organ systems developing 3rd trimester – greatest placental blood flow § Drugs known to have the potential to cause harm to the fetus are referred to as teratogenic § Many healthcare providers recommend that no drug should be used during pregnancy because of potential risk to the developing fetus. § Certain conditions may require drug therapy e.g. hypertension, epilepsy, diabetes, infection. Need to balance benefit & risk. 53 Check your understanding... True or False... 1. A contraindication is a condition when a drug should not be prescribed. 2. Polypharmacy is not a predisposing factor for adverse drug reactions. 3. Hypersensitivity is a type of adverse drug reaction. 54 http://i2.wp.com/avoidadr.citywide.tv/wp- content/uploads/sites/7/2015/06/2007_07_adverse_effect1.jpg?fit=356%2C276