Pharmacology PDF

Pharmacology Pharmacology is the study of drugs, including their actions and effects on physiological terms. It includes how the drug affects the body (pharmacodynamics) and how the body affects the drug (pharmacokinetics). Drug: Is a natural or synthetic molecule that exerts a biochemical a...

Pharmacology Pharmacology is the study of drugs, including their actions and effects on physiological terms. It includes how the drug affects the body (pharmacodynamics) and how the body affects the drug (pharmacokinetics). Drug: Is a natural or synthetic molecule that exerts a biochemical and/or physiological effect. The World Health Organisation defines a drug as: “any substance or product that is used or intended to be used to modify or explore physiological systems or pathological states for the benefit of the recipient” Drugs are derived from a variety of sources: Microorganisms Plants Animals Minerals Synthesised in labs Eg. The antibiotic penicillin is produced by a fungus 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 poppy plant (Papaver somniferum) for pain management Digoxin – derived from pruple fox glove (Digitalis purpurea) plant used to slow heart rate and treat congestive heart failure Caffeine – derived from the Caffea arabica plant 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 Inorganic Aluminium – antacids to settle stomachs salts Fluoride – to treat dental and prevent dental cavities  Iron – to treat anaemia Gold - treatment of rheumatoid arthritis to relieve joint pain and stiffness Drugs have several names Generic name Trade Chemical name The generic (non-proprietary) is The trade (proprietary) or brand Is a description of the chemical the abbreviated and approved name is selected by the drug composition of the drug and name given to a drug by the company selling the drug. identifies the drugs atomic and manufacturer to first develop Protected by a trademark. molecular structure, e.g. para- it, e.g. Paracetamol acetyl-amino-phenol C8H9NO2 The same drug can have several A generic name set by the TGA trade names when produced by a for use in Australia is an number of different Australian Approved Name manufacturers, e.g. Panadol, (AAN) Panamax, and tylenol Routes of administration The enteral (oral Medications absorbed via the gastrointestinal (GIT or enteral) system. route) 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 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 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) Sublingual and Sublingual administration-drug placed under tongue to dissolve(disperse) Buccal 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 The parenteral Any method of drug administration that avoids the gastrointestinal tract route 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 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) 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 or prongs and tubing, plus programmable infusion pump) Other routes of Inhalation (pulmonary route) administration Drugs administered by gas or fine mist. The lungs provide a large surface area for absorption.  Respiratory membrane and its rich capillary network allow 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. 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 Excreted from the body Absorption Distribution Metabolism Excretion 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 and must be absorbed before having any effect 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. 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 supply liver) → then into systemic circulation 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 o 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 o Highly vascularised area (e.g. the sublingual route) →more rapid absorption vs. poorly vascularised area (e.g. subcutaneous injection) → slower absorption o Patients with cardiovascular disease may have reduced blood circulation → slows absorption rate The solubility of a drug o 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 o lipid-soluble drugs → easily cross the plasma membrane via simple diffusion → rapid absorption o water-soluble drugs → cross the plasma membrane via facilitated diffusion or active transport → slower absorption 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 target 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 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. 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. Metabolism Metabolism, or biotransformation, is the process where drugs are broken down into substances that can be more easily excreted. These chemicals are called metabolites. Primary site: 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 Other medications, diet, alcohol, activity. Age and gender o Infants have immature liver function o The elderly show delayed metabolism of drugs o Pregnancy can alter drug metabolism Disease states o Heptic, renal or cardiovascular disease will slow metabolism 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 o Oral: Drugs administered orally undergo first-pass metabolism → bioavailability much lower than originally administered drug dose. o Intravascular: Drugs administered intravascularly do not undergo first- pass metabolism → bioavailability is 100% of originally administered dose of medication. Hepatic first-pass metabolism The oral dose of a medication is often higher than would be given intravascularly Process:  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. Example: A patient takes a 100mg dose of a drug 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 (eliminated) Only 20 % of the original dose reaches the systemic circulation This proportion that reaches systemic circulation is the remaining amount of drug available to exert a pharmacological effect – known as the BIOAVAILABILITY of the drug 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 Renal excretion The kidneys are the primary site of drug excretion from the body. o Free unbound drug can be filtered from the blood into the renal filtrate  o Lipid soluble drugs may be reabsorbed from the renal filtrate back into systemic circulation o 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 function cardiovascular function. Pharmacokinetics – how the body affects the drug (summary) Rational drug use: developing a drug 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. o Achieved by a drug dosage regime which includes o the amount of drug administered and o how often the drug is administered o Derived from information about populations of individuals and pharmacokinetic profile of the drug. o Important to remember not everyone responds to the same drug in the same way The therapeutic range lies between 2 concentrations: 1. The minimum effective concentration a. Minimum amount of drug required to cause a pharmacological effect 2. The minimum toxic concentration a. 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 3. Characteristics of an individual to consider o Age o Gender o Health/disease status o Cardiovascular, liver and kidney function 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 o e.g. IV administration of 100 mg of a drug that has a half life of 4 h: o After 4 h, 50 mg will remain in plasma o After another 4 h (or 8 h in total), 25 mg will remain... o The drug should be administered at regular time intervals to keep the plasma concentration within the therapeutic range 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 Pharmacodynamics The study of how the drug effects the body is called pharmacodynamics. It 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) o carrier proteins o ion channels o enzymes/chemical reactions o receptors DNA, i.e. chemotherapy drugs https://mhcbiofeedback.files.wordpress.com/2015/01/target.jpg 42 4 protein targets:  Effects on drugs on 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 Effects on drugs on 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 E.g. local anaesthetics block voltage gated sodium channels and inhibit the transmission of pain Effects on drugs on 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. Penicillin (acts on peptidoglycan wall in bacterial cells), Cyanide (toxic to humans) Effects on drugs on receptors Receptors are: present on the cell membrane and within the cytoplasm involved in signalling 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 Various drugs will bind cholinergic or adrenergic receptors and effect ANS function e.g. drugs that affect sympathetic functions Medication problems 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. 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 Prolonged illness Increased length of hospital stay Increased costs Higher mortality rates 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  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 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 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 Pharmacology foundation The nine rights of medication administration 1. Right patient 2. Right drug 3. Right route 4. Right time 5. Right dose 6. Right documentation 7. Right action 8. Right form 9. Right response Australian Medication Scheduling  Purchased off the shelf from a pharmacy (i.e. antihistamines). May be registered nurse or midwife initiated depending on hospital policy Schedule 2 (Pharmacy Medicine) Purchased from a pharmacy but requires advice from a pharmacist prior to administration (i.e. salbutamol). May be registered nurse or midwife initiated depending on hospital policy Schedule 3 (Pharmacist only Medicine) Medications that require a prescription from a doctor, nurse practitioner or certified midwife (i.e. antihypertensives, antibiotics, sleeping tablets, isotretinoin). Schedule 4 Storage: stored in a locked facility e.g. medication room, (Prescription only cupboard, trolley or patient bedside draw Medicine) Supply, storage, prescription and disposal are controlled by law (i.e. morphine, methadone, pethidine, fentanyl, oxycodone, cocaine mouthwash) Schedule 8 Storage: locked in a medication safe on wall or (Controlled Drug) floor to prevent theft Usage is restricted to analytical laboratories and trials Schedule 9 (i.e. heroin, cannabis, MDMA). (Prohibited substance) Includes some S4 and S8 medications that have the potential for abuse and dependence (i.e. midazolam, temazepam, tramadol). Schedule 11 Storage: locked in a medication safe on wall or (Drugs of Dependence) floor to prevent theft Record keeping Storage Medication name Generic name – abbreviated scientific name Trade name – brand or marketing name Drug learning websites: https://www.mimsonline.com.au/Search/Search.aspx Medication orders Medication orders are written on a medication drug chart or drug prescription pad Medication orders can also be given verbally from a prescriber to a nurse or midwife and confirmed in writing at a later stage A student nurse or midwife is not permitted to accept a verbal medication order form a prescriber Standing order: medication is administered according to this order until it is cancelled by another order/ceased Pro re nata (PRN) order: medication is administered as needed or requested according to the limits set in the med order STAT order: a single medication order that is carried out immediately, often during an emergency Verbal or telephone order: medication order is provided verbally by the prescriber when they are unable to attend to the patient directly Components of a valid legal prescription  Patients full, name, DOB, and UR number  Date and time the order was written  Generic name of medication to be administered  Dosage  Route of administration  Frequency of administration  Name, signature and contact number or prescriber  Indication (reason for prescription)  Legible and clear with no errors or omissions Medication administration Medication administration should be recorded on the drug chart as soon as possible after medication is given o Medication should never be signed as being administered until the full dose has been administered to the patient Route of administration should be recorded if variable routes were available on the prescription  If an injection is administered or a patch is applied at the site of the administration, then it should be recorded Relevant assessments may need to be documented on the medication chart or in the patient notes o Cardiovascular medications that are given when the patient’s pulse is higher than predetermined rate Common abbreviations UNITS OF MEASUREMENT FREQUENCY OF ROUTE OF ADMINISTRATION ADMINISTRATION g = gram PO = by mouth mg = milligram BD = twice a day Subcut = subcutaneous microg = microgram TDS = three times a day Subling = sub lingual L = litre PRN = as required Buccal = buccal mL = millilitre QID = four times a day IV = intravenous units = units Mane = morning IM = intramuscular tab = tablet Nocte = at night PV = per vagina caps = capsules Midi = midday PR = per rectum AC = before meals PC = after meals