Lecture Outline • Introduction • Legislation • Medication stability • Security • The cold chain • Naming, sources and formulations of drugs • Pharmacokinetics and pharmacodynamics • Responses to drug admin • Special considerations • Drug information • Safe and effective patient care Introduction • Drug expenditures in Canada is presumed to reach 33.9 million or 16% of Canada’s health care budget in 2014 • Paramedics are responsible to provide appropriate drug therapy to patients • What other roles can the paramedic play in a patients medication management? Determining adherence? Educator? – Utilize the time spent with the patient • Medication management – “Medication management is defined as patient-centred care to optimize safe, effective and appropriate drug therapy. Care is provided through collaboration with patients and their health care teams.” • Drug therapy Legislation • Government creates acts • Health Canada develops regulations based on Acts – Drugs are assigned drug identification numbers (DIN) – Natural health products are assigned a natural product number (NPN) or drug identification number-homeopathic medicine (DIN- HM) – Controlled Drugs and Substances Act Legislation Health Canada Health Canada Food and Drug Act 1. Therapeutics Health Products Directorate Drug and Health 2. Natural and Non-prescription Health Products Directorate Products Legislation Schedules A-H Canadian Food and Drug Act A List 36 diseases that no item can be advertised or sold as a CURE (cancer, gangrene, alcoholism…) B Lists the books of standards (CPS, US Pharmacopoeia) C Lists liver extract products D Lists drugs prepared from microorganisms and antibiotics for parenteral use E Lists sensitivity disc or tablets that cannot be sold unless each lot produced has been governmentally F Lists over 200 drugs that may not be used except after professional consultation Lists non-narcotic drugs that require prescription for use G Lists drugs that affect the CNS (Sedatives and Narcotics), controlled because of abuse potential H Lists drugs with no recognized medical use with significant danger (LSD) Medication labelling Pr = Schedule F drug, for Human use Other targeted substance Narcotic, Schedule G Medication Stability • Drugs do not spontaneously degrade, they generally need a catalyst in the form of heat, vibration and light; all of which EMS provide in sufficient quantity • Stability: the extent to which a pharmaceutical product possessed the same physical and chemical properties and characteristics that was possessed at the time of its manufacture. Generally we are looking for 90% retention of the active ingredient • What can we do in EMS to prevent degradation and potentially negative patient outcomes? Security • No drug act regulation stating specific security requirements above generic “take all reasonable requirements to ensure security of narcotics and controlled substances” • Due diligence would stipulate a need for record keeping to ensure stock does not go missing • If a theft, loss or forgery occurs it must be reported to the local police immediately and to the Office of Controlled Substances no later than 10 days after its discovery • The Office of Controlled Substances (OCS) works to ensure that drugs and controlled substances are not diverted for illegal use Security The Cold Chain • Many medications and vaccines require a cold chain to exist between the manufacturer and the end user • These medications must be refrigerated which the USP defines as a temperature between 2-8˚C • If products requiring refrigeration are exposed to temperature flux outside of this range it can lead to loss of stability and denaturation • The health care team and the confidence in the medications and vaccines they use can be lost if the cold chain is broken and the medication is not effective (anti-vaxxers) CDHA Cold Chain Policy • Manufacturer, distributor, policy makers, medical staff all have role to play Pharmacological Terminology and Abbreviations • Transcription a.k.a. SIG – SIG = Signa = Signature = label or mark them. – The SIG represents the instructions that will be placed on the Rx label Naming of Drugs • Chemical – States its chemical composition and molecular structure • Generic – Often abbreviated form of chemical name • Brand – The trade or proprietary name • Official Name – Followed by abbreviation to which drug standard conforms to – USP, NF Names of Drugs 7-chloro-1, 3-dihydro-1 Chemical Name methyl-5-phenyl-2h-1, 4-benzodiazepin-2-one Generic Name Diazepam Brand Name Valium® Diazepam, USP Official name Chemical name Diazepam Midazolam 7-chloro-1, 3-dihydro-1 methyl-5-phenyl-2h-1, 4- 8-chloro-6-(2-fluorophenyl)-1-methyl-4H-imidazo[1,5- benzodiazepin-2-one a][1,4]benzodiazepine Sources of Drugs • Drug are chemical agents used in the diagnosis, treatment, or prevention of disease and come from a variety of sources • Plants – Possibly the oldest source of medications • Atropine from the “deadly nightshade” • Digoxin from foxglove • ASA from the bark of willow trees • Animals – Hormones, enzymes, fluids • Insulin, glucagon, cod liver oil, pepsin, pancreatin Sources of Drugs • Minerals – Metallic or nonmetallic minerals provide various inorganic material not available from plants or animals • Magnesium sulphate and calcium chloride • Laboratory (synthetic) – Many new drugs produced in the laboratory – Recombinant DNA technology • Reordering genetic information allows researchers to develop bacteria that produce human hormones Drug Forms • Solid Forms: – Such as pills, powders, suppositories, capsules and tablets • Liquid Forms: – Such as solutions, tinctures, suspensions, emulsions, spirits, elixirs and syrups – Emergency medication packaging • Vials, ampules, self-contained systems or syringes, nebules Solid Forms • Pills – Drugs shaped spherically to be swallowed. • Powders – Not as popular as they once were. • Tablets – Powders compressed into disk-like form. • Suppositories – Drugs mixed with a wax-like base that melts at body temperature. • Capsules – Gelatin containers filled with powders or tiny pills. Liquid Forms • Solutions – Water or oil based. • Tinctures – Prepared using an alcohol extraction process. • Suspensions – Preparations in which the solid does not dissolve in the solvent. • Emulsions – Suspensions with an oily substance in the solvent. Liquid Forms • Spirits – Solution of a volatile drug in alcohol. • Elixirs – Alcohol and water solvent; often with flavoring. • Syrups – Sugar, water and drug solutions. Emergency Packaging Styles nebule ampules Single dose Multi dose Pharmacokinetics vs Pharmacodynamics • Pharmacodynamics – Refers to how the drug affects the body • Pharmacokinetics – Refers to how the body affects the drug Pharmacokinetics • Absorption • Distribution • Metabolism • Elimination Pharmacokinetics Absorption, Distribution, Metabolism (biotransformation), Elimination = ADME Slope representing absorption Slope representing elimination AUC = Bioavailability Absorption • The movement of a drug from its site of administration towards its site of action, if a drug is given PO or injected into any other place other than the bloodstream, entering into the bloodstream is the Plasma concertation vs time profiles of Alfentanil and Midazolam after administering first step in the process (A) IV Midazolam, (B) IV Alfentanil, (C) PO Midazolam, (D) PO Alfentanil Absorption • Factors affecting absorption Solubility The ability of the medication to dissolve. Fat soluble drugs can cross blood brain barrier but water soluble drugs, like penicillin, cannot PH Acidic drugs better absorbed in acidic environment and basic drugs better absorbed in basic environment Surface area The larger the surface area the more absorption Blood supply Medications absorb more rapidly from areas with a rich blood supply Concentration Simple diffusion Molecular size of drug Larger drugs not absorbed as efficiently Enteral vs Parenteral • Enteral are medications absorbed via the gastrointestinal tract – Does not mean they all go through first pass metabolism • Parenteral are medications entering via all other routes Enteral Parenteral Parenteral (Topical) • Per Os (PO) - is Latin for by mouth • Intravenous (IV) • Percutaneous • Sublingual (SL) • Intramuscular (IM) • Ocular • Rectal (PR) • Subcutaneous (SQ) • Nasal • Orogastric • Intraosseous (IO) • Respiratory (OG)/Nasogastric (NG) • Umbilical • Buccal (BUC) Rectal Drug Absorption A • Example of the contrast between circumventing and entering portal B circulation – Hence, rectal absorption can be erratic C • Drugs can be utilized via this route to treat local (hemorrhoids) or systemic (diazepam for seizures) A. Superior rectal vein drains into the mesenteric conditions vein which drains into portal vein B. Middle rectal vein drains into vena cava C. Inferior rectal vein drains into vena cava Distribution • The process by which a medication is transported from the site of absorption to the site of action • Must permeate physiological barriers • Depends on physiochemical properties of drug – Meningitis, must have a drug that distributes to cerebrospinal fluid – Skin/soft tissue infections, medication the can distribute to the dermis • Volume of distribution (Vd) – the apparent volume a drug could occupy – Chloroquine • 15000L • Plasma =4-6L – High Vd means drug distributes extensively into and retained within plasma and tissues Distribution Several factors can affect medication distribution • Cardiovascular function • In the body medications can be stored • Regional blood flow at various sites • Medication storage reservoirs • Drugs can be transported on plasma • Physiological barriers proteins – Albumin, Alpha1-acid glycoprotein – Blood-brain barrier – Blood-retinal barrier Free Drug Bound drug – Placental barrier Can be eliminated Cannot be eliminated Can exert pharmacological Cannot exert pharmacological effect effect Can bind to receptors Bound to protein Can distribute Concentration in tissues limited Metabolism (Biotransformation) • First pass metabolism – Portal circulation • Circulatory circuit connecting two different tissues but not going to the heart in between • Hepatic portal circulation – nutrient rich blood (also carrying medication) is absorbed in intestine and brought to liver before entering systemic circulation • Hepatic and intestinal enzymes (cytochrome P450) • The liver (and to a lesser degree the intestine) can affect how much of a medication that was absorbed in the intestine will enter circulation, resulting in reduced concentration of drug NTG Understanding Metabolism Via the Prodrug • Pharmacogenetics is an emerging • A prodrug is a drug that needs to be science, certain people are fast, activated by being metabolized normal or poor metabolizers in certain – Codeine is not an active drug but the liver enzyme pathways turns it into its active form, morphine. Most drugs are deactivated by metabolism Slow metabolizer Active = +++ codeine Fast metabolizer = +++++ morphine Elimination • Half life (T½) – Rate of elimination of drug, time required to eliminate 50% of drug – Drug is said to be cleared after 5 half lives • Clearance – The bodies ability to remove a medication from systemic circulation • Medications are eliminated from the body in their original form or more often as metabolites • What organs are responsible for elimination and the medium of elimination? • What happens to T½ if your patient receives a drug eliminated by the kidney and they have renal failure? Pharmacodynamics • How does the drug work on the body • When we talk about pharmacodynamics we generally use a reversible drug-receptor model (lock and key) – The relationship between drug and receptor is due to molecular weight, shape, and electrical charge of a drug – Drugs binding to receptors the most common means of inducing pharmacological effect • Receptors responsible for selectivity of action • Once medications reach their targeted tissues, they begin a chain of biochemical events that ultimately leads to the physiological changes desired. These biochemical and physiological events are referred to as the mechanism of action. Agonist & Antagonist Partial agonist Non-competitive inhibitor • The force of attraction between a medication and its receptor is called their affinity. • The greater the affinity the stronger the bond. • Different drugs may bind to the same receptor site but with different strengths or affinity. Dose-Response Curve, Potency and Efficacy More potent • Dose on X axis and response on Y axis • Efficacy is the ability of a medication to product a clinical response Same – Efficacy more important clinically than efficacy potency • Medication potency refers the relative amount of medication required to product the desired response – The potency of a drug is when the concentration of drug induces 50% of maximal response More efficacious Pharmacodynamics • Therapeutic Index (TI): • TI = LD50 / ED50 • Lethal Dose (LD) in 50% of lab animals/Effective Dose (ED) in 50% of human trial subjects • Measures the drugs safety. TI’s close to 1 have a small margin of safety ie: digoxin Therapeutic Window • The relation of the therapeutic window of drug concentrations to the therapeutic and adverse effects in the population. The ordinate is linear; the abscissa is logarithmic. Wide Therapeutic Index Narrow Therapeutic Index • Other commonly encountered drugs: • Warfarin • Digoxin • Phenytoin Therapeutic Index • Calculate the TI: • If the standard dose of the drug Dilantin is 100 mg and if 3000 mg has been deemed as the expected lethal dose, what is the TI of this drug considered to be ? Factors Affecting Drug Response • Age • Time of Administration • Body Mass • Pathology • Sex • Genetics • Environment • Psychology Responses to Drug Administration • Side Effect – Unintended response to a drug. • Allergic Reaction – Hypersensitivity. • Idiosyncrasy – Drug effect unique to an individual. • Tolerance – Decreased response to the same amount Responses to Drug Administration • Cross Tolerance – Tolerance for a drug that develops after administration of a different drug. • Cumulative effect – Increased effectiveness when a drug is given in several doses • Tachyphylaxis – Rapidly occurring tolerance to a drug • Drug dependence – Psychological vs physical – Patient becomes accustomed to the drug’s presence in his body. Cross Tolerance Responses to Drug Administration • Summation – Also known as additive effect, two drugs with the same effect are given together (1+1=2) • Synergism – Two drugs with the same effect are given together and produce a response greater than the sum of their individual responses (similar to 1+1=3) • Potentiation – One drug enhances the effect of another. • Interference – The direct biochemical interaction between two drugs; one drug affects the pharmacology of another drug. Drug Interactions • Drug interactions have the possibility to occur whenever two or more drugs are available in the same patient • The interaction can increase, decrease, or have no effect on their combined actions. Special Considerations • Pregnant and breast feeding patients • Pediatric patients • Geriatric patients Pregnant Patients • Ask the patient if there is a possibility that she could be pregnant. • Teratogen is a substance that has the potential under certain exposure conditions to cause abnormal development in the fetus • Physiological changes in pregnant women: – Increased cardiac output – Increased HR – Increased blood volume – Decreased protein binding – Decreased hepatic metabolism – Increased renal excretion Pregnant Patients Breastfeeding Pregnancy categories • Breast milk has been identified as the optimal source of nutrition for infants, but with benefits conferred to mothers, families, and societies. • Passive of drug occurs through passive diffusion – Less likely with protein bound, large, water soluble drugs – Heparin, insulin – high molecular weight drug not likely to cross More data on older medications Pregnant Patients • New pregnancy categories – Dec. 2015 - “The U.S. Food and Drug Administration published a final rule today that sets standards for how information about using medicines during pregnancy and breastfeeding is presented in the labeling of prescription drugs and biological products. The new content and formatting requirements will provide a more consistent way to include relevant information about the risks and benefits of prescription drugs and biological products used during pregnancy and breastfeeding.” – “The final rule replaces the current product letter categories – A, B, C, D and X – used to classify the risks of using prescription drugs during pregnancy with three detailed subsections that describe risks within the real-world context of caring for pregnant women who may need medication” Pediatrics • Pediatric medication dosages are typically based on the child’s body weight or body surface area (BSA) • Important to ascertain pediatric patients weight or use a Broselow Tape • Absorption in altered and does not reach adult levels until several months – Stomach acid PH is higher meaning increased absorption of acid labile drugs • Gastric emptying is delayed – Adult levels not reached until up to 8 months • Decreased circulating plasma albumin, which leads to what? • The development of liver metabolic enzyme function continues during the first years of life and does not appear to be at adult levels until after puberty • Renal filtration, absorption, and secretion not fully functional until 1 year of age Geriatric Patients • More apt to suffer from comorbidities – Growing segment of population • Physiological effects of aging: – Decreased cardiac output (decreased distribution) – Decreased total body water, decrease lean body mass • Drugs that distribute into these tissues can result in higher levels (digoxin) – Increase in total fat • Lipid soluble drugs such as diazepam can accumulate, and result in lower blood concentrations – Decreased serum albumin (decreased distribution) – Decreased renal function • Causes more adverse drug reactions than other physiological changes • Increases half life of drug • Greatest concern with drugs 100% renally cleared – Decreased respiratory capacity • As a general rule no change in absorption of drugs via GI tract Drug Information, Components of a Drug Profile • Name • Routes of • Classification administration • Mechanism of • Contraindications action • Dosage • Indications • How supplied • Pharmacokinetics • Special • Adverse drug reactions considerations Sources of Drug Information • Monographic resources – Compendium of Pharmaceuticals and Specialties (CPS), now electronic (e-CPS) • 6 sections – Lexicomp, Micromedex, Martindale • Health Canada Drug Product Database – DIN, drug identification number • Gives manufacturer, routes of admin, schedule, strength • Natural Health Products Directorate – Now Non-prescription Health Products Directorate (NNHPD) Sources of Drug Information • Special patients – Pregnancy and lactation • Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk by Briggs • Drugs During Pregnancy and Lactation: Treatment Options and Risk Assessment by Schaffer • Motherisk, from The Hospital for Sick Children, www.motherisk.org • Drugs and Lactation, LACTMED, http://toxnet.nlm.nih.gov/newtoxnet/lactmed.htm • Compatibility of injectable drugs – Trissel’s stability of compounded formulations, which can be accessed from lexicomp OR available as a hard copy by Lawrence A. Trissel – Kings Guide to parenteral admixtures, which can be accessed from Micromedex • Medication standards – United States Pharmacopeia (USP) and National Formulary (NF) • Electronic – British Pharmacopeia Monographs Drug Product Database E-CPS Sources of Drug Information Vitamins & Natural Health Products Science vs home remedies vs Facebook. More than meets the eye “The failure of vitamin C supplementation to reduce the incidence of colds in the general population indicates that routine vitamin C supplementation is not justified, yet vitamin C may be useful for people exposed to brief periods of severe physical exercise.” Toxic upper limit of vitamin C is 2000 mg/day Safe and Effective Patient Care • Know the precautions and contraindications for all medications you administer. • Know how to observe and document drug effects. • Maintain a current knowledge in pharmacology • Establish and maintain professional relationships with other healthcare providers. • Understand pharmacokinetics and pharmacodynamics • Have current medication references available Safe and Effective Patient Care • As a PCP you may be called upon by your ALS partner to administer medications under their supervision • This will require you to have an understanding of medications outside of your scope • Ensure you verify what you are doing with your ALS partner who is authorizing you to administer a medication out of your scope of practice – Closed loop communication • Do not hesitant to ask questions or for partner to clarify Safe and Effective Patient Care • Take careful drug histories including: – Name, strength, dose of prescribed medications; • Ask about Abx used within last 3 month, excellent information to give hospital staff if patient has an infection – Over-the-counter drugs • Look at the active ingredients, you may be surprised – Vitamins – Herbal medications/folk remedies – Allergies • Evaluate the patient’s adherence, dosage and adverse reactions • Consult with medical direction as needed Documentation • The drugs you administer in the field do not stop affecting your patients when those patients enter the hospital. • As a result, you must completely document all of your care, especially any drugs you have administered, so that long after you have left for your next call, other providers will know what drugs your patients has been administered • Include the medication, time administered, dose, route, amount discarded, effect (therapeutic or adverse), sign/initial and include medic number