1.Introduction to Pharmacology Introduction to Pharmacology By: Robert S. Cole CWI Paramedic Class 2014

2. Learning Objectives Describe pharmacological as a science and a historical perspective Differentiate chemical, generic, trade names of drug List main sources of drug products Describe how drugs are classified List authoritative sources for drug information List legislative acts controlling drug use, abuse in U.S. Differentiate Schedule I, II, III, IV, V substances; list examples Discuss standardization of drugs Discuss paramedics s responsibilities and scope of management pertinent to administration of medications 3. Introduction What is a drug? What is pharmacology? Why is it important? 4. Introduction Drug : Substance (chemical agents) intended to diagnose, cure, relieve, treat, prevent disease Affects structure/function of body Pharmacology : Study of drugs 5. Things that make you go hmmmmm Based on Greek: pharmakon: poison in classic Greek; drug in modern Greek"; - logia: "Study of" 6. Introduction Written records of drug use date back to the ancient Egyptians Early writings on drugs were observational, and were not based on science Early pharmacologists focused on natural substances, mainly plant extracts. The theories of Humors were used for almost 2000 years. It wasnt until the19th century that Pharmacology developed as a biomedical science that applied the principles of scientific experimentation to therapeutic contexts. 7. Three Early Pharmacists Hippocrates Claudius Galen Pedanius Dioscorides 8. The Renaissance and Phamacology After Roman Empire fall, most European cultures reverted to folklore, tradition, superstition By contrast: Muslims, Greeks, Italians/Romans, Jews combined knowledge of math, science, created formularies Monasteries became some of the earliest learning centers for pharmacy, medicine 9. Modern Pharmacology Pharmaceutical laws enacted late 19th, early 20th century protecting public Drugs developed improved chronic illness treatment 1950-current, more changes in pharmacology than any other time 10. Introduction Subspecialties of Pharmacology Pharmacokinetics Pharmacodynamics Pharmacogenetics Pharmacogenomics Pharmacogenosy 11. Pharmacokinetics vs. Pharmacodynamics Pharmacokinetics describes the movement of the drug throughout the body. The bodys effect on the drug (e.g. half- life and volume of distribution), Pharmacodynamics described the effects of the drug on the body, intentional or toxic Side effects, MOA, desired effects, etc 12. Pharmacokinetics When describing the pharmacokinetic properties of a chemical, pharmacologists are often interested in LADME: Liberation - disintegration (for solid oral forms {breaking down into smaller particles}), dispersal and dissolution Absorption - How is the medication absorbed (through the skin, the intestine, the oral mucosa)? Distribution - How does it spread through the organism? Metabolism - Is the medication converted chemically inside the body, and into which substances. Are these active? Could they be toxic? Excretion - How is the medication eliminated (through the bile, urine, breath, skin)? 13. Pharmacokinetics This includes Active transport Facilitated diffusion Passive transport 14. Pharmacokinetics Active Transport Use of energy (typically ATP) across barrier (i.e. membrane) into target tissue. Also may involve other ions Typically this is against a pressure gradient (or else passive transport would work) 15. Pharmacokinetics Facilitated diffusion (also known as facilitated transport or passive-mediated transport) Passive transport with a twist Cell walls have specific properties that allow passive transport of certain molecules and not others. Polarity Size Protein assisted : Channels 16. Pharmacokinetics Pharmacokinetics considerations Molecule size and shape Solubility in water and lipids Ability to bind to tissue proteins Ionization 17. Pharmacodynamics Drugs may act in four different ways: Bind to a receptor site Change the physical properties of the cell Chemically combine with other chemicals Alter a normal metabolic pathway 18. Pharmacogenetics and pharmacogenomics Pharmacogenetics and pharmacogenomics Study unique genetic processes linked to DNA coding and genetics 19. Pharmacogenosy The study of natural drug sources Plants Animals Minerals What are some common examples of each drug source? 20. Did you know? Crude Drugs: A crude drug is any naturally occurring, unrefined substance derived from organic or inorganic sources such as plant, animal, bacteria, organs or whole organisms intended for use in the diagnosis, cure, mitigation, treatment, or prevention of disease in man or other animals. Crude drugs are unrefined medications in their raw or natural forms. Prior to the 1950s, every pharmacy student learned about crude drugs in pharmacognosy class. Pharmacognosy is the study of the proper horticulture, harvesting and uses of the raw medications found in nature. By the 1980s, this practice was discontinued in most western pharmacology programs, increasing the reliance of pharmacist on drug companies. Raising, harvesting and selling crude drugs was how many large pharmaceutical companies started out. Companies such as Eli Lilly and Company sold crude drugs to pharmacists to save them time and money, but the early pharmacy graduate would know how to raise their own crude drugs if need be. 21. Plant Sources of Drugs Oldest source of medications Drugs may consist of using the entire plant, leaves, roots, bulbs, stems, seeds, buds, or blossoms 22. Where do Drugs come from? 23. Animal Sources of Drugs Body fluids or glands from animals can act as sources for drugs Hormones Oils and fats Enzymes 24. Mineral Sources of Drugs Metallic and nonmetallic minerals provide various inorganic materials Occur naturally or are combined to form acids, bases, or salts 25. Orphan Drugs An orphan drug is a pharmaceutical agent that has been developed specifically to treat a rare medical condition, the condition itself being referred to as an orphan disease. Development, production, and marketing of an orphan drug is not considered profitable under traditional pharmaceutical business models, and therefore would likely not occur without incentives. The assignment of orphan status to a disease and to any drugs developed to treat it is a matter of public policy in many countries and the World Health Organization (WHO), and has resulted in medical breakthroughs that may not have otherwise been achieved due to the economics of drug research and development. In the US and EU it is easier to gain marketing approval for an orphan drug, and there may be other financial incentives such as extended exclusivity periods. 26. Introduction Laboratory-produced drug sources New drugs may be a more pure form of a naturally occurring drug or they may be a synthetic form Or a combination i.e. Morphine vs. Fentanyl 27. Routes of Administration 28. Routes of Administration Routes of Administration Enteral Route Parenteral Route Topical Route 29. Routes of Administration Subroutes of administration Ingestion Injection Absorption Inhalation 30. Route of Administration Depends of many factors Accessibility Rate of absorption Deactivation by enzymes or acids Toxicity to tissues 31. Routes of Administration Enteral Orally (PO) Parenteral (just a few) Intramuscular (IM) Subcutaneous (SC or SQ) Intravenous (IV) Inhalation Sublinqual 32. Local vs. systemic effects Local effect Affects specific body part Systemic effect Affects entire body 33. Common Routes Oral (PO) Slow Intra-Dermal (ID) Slow Subcutaneous (SQ) Slow Topical /Trans Dermal (TD) Moderate Intramuscular (IM) Moderate Rectal (PR) Rapid Sublingual (SL) Rapid Endotracheal (ET) Rapid Inhalation Rapid Intra-Nasal (IN) Rapid Intraosseous (IO) Immediate Intavenous (IV) Immediate 34. Drug Absorption Drugs progress from its pharmaceutical dosage form to a biologically available substance Several factors affect drug absorption 35. Basic Principles of Pharmacology 36. Factors 1. Solubility 2. Concentration 3. pH 4. Site of absorption 5. Blood supply 6. Bioavailability 37. Bioavailability Bioavailability (BA) is a subcategory of absorption and is used to describe the fraction of an administered dose of unchanged drug that reaches the systemic circulation By definition, when a medication is administered intravenously, its bioavailability is 100%. However, when a medication is administered via other routes (such as orally), its bioavailability generally decreases 38. Bioequivalence The absence of a significant difference in the rate and extent to which the active ingredient or active moiety in pharmaceutical equivalents or pharmaceutical alternatives becomes available at the site of drug action when administered at the same molar dose under similar conditions in an appropriately designed study The US FDA 39. Biotransformation Biotransformation has two effects: It can transform the drug into a more or less active metabolite It can make the drug more water soluble (or less lipid-soluble) to facilitate elimination 40. Biotransformation Can activate metabolites to make the drug active (prodrugs) Many processes occur in the liver First-pass effect Body detoxifies and disposes of toxins and excess drug by increasing water solubility 41. First Pass Metabolism The first-pass effect (AKA first-pass metabolism or presystemic metabolism) is a phenomenon of drug metabolism whereby the concentration of a drug is greatly reduced before it reaches the systemic circulation. It is the fraction of lost drug during the process of absorption which is generally related to the liver and gut wall. Notable drugs that experience a significant first-pass. After a drug is swallowed, it is absorbed by the digestive system and enters the hepatic portal system through the portal vein to the liver. The liver metabolizes many drugs, sometimes to such an extent that only a small amount of active drug emerges from the liver to the rest of the circulatory system. This first pass through the liver thus greatly reduces the bioavailability of the drug. Alternative routes administration like suppository , intravenous, intramuscular, inhalational aerosol and sublingual avoid the first-pass effect because they allow drugs to be absorbed directly into the systemic circulation. 42. Distribution Several factors affect distribution: Cardiovascular function Regional blood flow Drug storage reservoirs Physiological barriers 43. Physiologic Barriers Blood Brain Barrier/Placental barrier 44. BLOOD BRAIN BARRIER The blood- brain barrier is located in endothelial cells of capillaries of the brain. The blood brain barrier is both a physical barrier and a system of cellular transport mechanisms. It maintains homeostasis by restricting the entrances of potentially harmful chemicals from the blood, and by allowing the entrance of essential nutrients. 45. BLOOD BRAIN BARRIER Lipid soluble molecules, (i.e. ethanol , most opioids, and caffeine) are able to penetrate through the barrier relatively easily via the lipid membranes of the cells. In contrast, water soluble molecules such as sodium and potassium ions are unable to transverse the barrier without the use of specialized carrier- mediated transport mechanisms. 46. BLOOD BRAIN BARRIER These endothelial cells of capillaries in the brain are different to those found in peripheral tissues in various ways: Brain endothelial cells are joined by tight junctions of high electrical resistance providing an effective barrier against molecules. In peripheral endothelial cells there is good transcellular movement of molecules. There is no such movement in brain endothelial cells. Brain capillaries are in contact with foot processes of astrocytes which essentially separate the capillaries from the neurones. 47. Astrocyte Feet? 48. 3 places w/ no BBB Incomplete until 1-2 yrs Hypothalamus/ 49. Therapeutic Index Medication must reach a certain concentration at the target tissue to be effective Therapeutic index Therapeutic threshold 50. Therapeutic Index Dose calculation ED50 LD50 TD50 51. Elimination Can be affected by Drug half-life Accumulation Clearance Onset, peak, and duration 52. Accumulation Accumulation: a drug that is not re- administered is eliminated almost completely over time, but a regularly administered remains constant. When elimination is altered, accumulation increases. In some cases this results in a drug exceeding its therapeutic window. Tylonol is a common drug with this problem. Opioids as well. 53. Half Life Technically a biological half life or elimination half-life In a medical context, half-life may also describe the time it takes for the blood plasma concentration of a substance to halve ("plasma half-life") its steady-state. The relationship between the biological and plasma half-lives of a substance can be complex, due to factors including accumulation in tissues, active metabolites, and receptor interactions. 54. Question Is the Half Life of a drug is 6 hours, how long does it take to eliminate 98% the drug from the body? 55. KEY POINT IT TAKES SIX HALF LIVES TO REACH 98% ELIMINATION So it would take 36 hours for the hypothetical drug to be (mostly) eliminated 56. Basics Drugs are eliminated in either their original form or as metabolites Drug excretion is the movement of a drug or its metabolites from the tissues back into circulation and from secretion into organs of excretion 57. Drug Forms 58. Drug Forms Usually consist of a powder dissolved in a liquid Solute: drug Solvent: liquid in which it is dissolved, typicaly water Primary difference between one preparation and another is the solvent What is a solution? 59. Drug Forms Liquids Solids Suppositories Inhalants Sprays Creams/lotions Patches Lozenges 60. Liquid Drugs Solutions: preparations that contain a drug dissolved in a solvent, usually water. Tinctures: drugs chemically extracted from alcohol. Suspensions: drugs that do not remain dissolved in a solution. Spirits: drugs that contain volatile chemicals dissolved in alcohol. Solutions: preparations that contain a drug dissolved in a solvent, usually water. Tinctures: drugs chemically extracted from alcohol. Suspensions: drugs that do not remain dissolved in a solution. Spirits: drugs that contain volatile chemicals dissolved in alcohol. 61. Liquid Drugs Emulsions: an oily substance is mixed with a solvent into which it doesnt dissolve. Elixirs: a drug in an alcohol solvent. Syrups: drugs suspended in sugar and water to improve the taste. 62. Packaging Packaging and preparations Vials Ampules Self-contained systems or syringes Nebules 63. Solid Drugs Administered orally or rectally Pills: shaped into a form Powders: dry, particulate form of drug Capsules: gelatin container filled with powder Tablets: compressed powder covered with sugar coating Suppositories: carried in a solid base that melts at body temperature Administered rectally or vaginally Produce local and systemic effects 64. Inhalants Both powdered or liquid forms of a drug given via the respiratory route and absorbed by the capillaries in the lungs. Nebulizers Metered-dose aerosols Turbo inhalers Vaporizers 65. Take a Break. 66. Receptors 67. Receptors Mechanism of Action: how a drug works Drug action Drug effect 68. Receptors Drug receptors: proteins present on cell membrane to which a drug must bind in order to elicit a desired response 69. Receptors Receptors are classified based on effects Agonist AKA Memetic Antagonist Competitive antagonist Noncompetitive antagonist AKA -lytic A drug attached to a receptor site displays affinity 70. Receptors 71. Receptors Efficacy: the power of a drug to produce a therapeutic effect Agonists have affinity and efficacy Antagonists have affinity but not efficacy Drug potency: relative amount of drug required to produce the desired response 72. Receptors How do drugs bind to receptor sites? Ionic bonds: chemical bonds in which ions are transferred from one molecule to another so that one end is positive and the other negative Hydrogen bonds: bonds that share a hydrogen ion between molecules Hydrophobic bonds nonpolar bonds created between molecules Van der Waals forces: transient, weak electrical attraction of one atom for another that allows a molecule to change shape Covalent bonds: chemical bond between two atoms achieved by sharing pairs of electrons 73. Receptors Receptor sites Several drugs may bind to the same receptor site, thus creating different responses by the cells Two main functions Ligand binding Message propagation 74. Neurotransmitters 75. Neurotransmitters The nervous system is the bodys control system, regulating all bodily function via electrical impulses What are the two main parts of the central nervous system that drugs can affect? 76. Neurotransmitters Two divisions: Central Nervous System (CNS) Peripheral Nervous System (PNS) 77. Neurotransmitters 78. Neurotransmitters Organ Sympathetic stimulation Parasympathetic stimulation Heart Increased rate, force Decreased rate, force Lungs Bronchodilation Bronchoconstriction Kidneys Decreased output None Systemic blood vessels Constricted a dilated b None Liver Glucose release Glycogen synthesis Blood glucose Increased None Pupils Dilated Constricted Basal metabolism Increased up to 100% None Skeletal muscle Increased strength None 79. Neurotransmitters Nerves of the autonomic nervous system exit the CNS and enter autonomic ganglia 80. Neurotransmitters No connection exists between two nerve cells or a nerve cell and its target organ; instead there is a space called a synapse Neurotransmitters are specialized chemicals that conduct impulses between nerve cells or between a nerve cell and an organ 81. Neurotransmitters Neurotransmitters of ANS: Acetylcholine (Ach) Norepinephrine (NE) Synapses: Cholinergic synapses: use acetylcholine Adrenergic synapses: use norepinephrine 82. Neurotransmitters What is the action of an adrenergic drugs? What is the action of a cholinergic drug? 83. Neurotransmitters Cholinergic receptors Acetylcholine Interacts with receptors, physiologic response Sympathetic receptors (Adrenergic receptors) When sympathetic division stimulated, adrenal medulla stimulated, releases epinephrine into circulatory system Sympatho-mimetic Sympatho-lytics 84. Neurotransmitters Sympathetic Nervous System Arises from the thoracic and lumbar regions of the spinal cord Results in direct stimulation of adrenal medulla and release of norepinephrine (noradrenaline) and epinephrine (adrenaline) 85. Neurotransmitters Sympathetic Nervous System Stimulation ultimately results in release of norepinephrine from postganglionic nerves Sympathetic stimulation also results in release of epinephrine and norepinephrine from the adrenal medulla What is/are the chemical mediators of the SNS? 86. Neurotransmitters Types of sympathetic receptors What is the action of adrenergic receptors? Alpha1 (a1) Alpha2 (a2) Beta1 (b1) Beta2 (b2) Of dopaminergic receptors? 87. Neurotransmitters alpha1 (a1) Peripheral vasoconstriction, increased contractile force, decreased rate alpha2 (a2) Peripheral vasoconstriction beta1 (b1) Increased heart rate, contractile force and automaticity beta2 (b2) Peripheral vasodilation, bronchodilation, uterine smooth muscle relaxation dopaminergic Renal vasodilation and mesenteric vasodilation Receptor Actions 88. Neurotransmitters Sympathomimetics: medications that stimulate the sympathetic nervous system Sympatholytics: medications that inhibit the sympathetic nervous system 89. Neurotransmitters The Parasympathetic Nervous System Arises from the brain stem and sacral segments of the spinal cord Synapse in parasympathetic ganglia What is/are the chemical mediators of the PNS? 90. Neurotransmitters Stimulation of the parasympathetic nervous system results in: Pupillary constriction Secretion by digestive glands Increased smooth muscle activity along GI tract Bronchoconstriction Reduction in heart rate and contractile force 91. Neurotransmitters Parasympatholytics: medications that block the actions of the parasympathetic nervous system Parasympathomimetics: medications that stimulate the parasympathetic nervous system 92. Homeostasis and Balance 93. Homeostasis and Balance Our bodies require constant regulation in order to maintain balance and control 94. Legal Concerns and Drugs 95. Legal Concerns Legal regulations, standards, and legislation International controls United Nations World Health Organization provides technical assistance and encourages new research for drug use US Controls The FDA and the DEA share responsibility and enforcement 96. The FDA In the United States, the Food and Drug Administration (FDA) is responsible for creating guidelines for the approval and use of drugs. The FDA requires that all approved drugs fulfill two requirements: The drug must be found to be effective against the disease for which it is seeking approval. The drug must meet safety criteria by being subject to extensive animal and controlled human testing. Gaining FDA approval usually takes several years to attain. Testing done on animals must be extensive and must include several species to help in the evaluation of both the effectiveness and toxicity of the drug. The dosage of any drug approved for use is intended to fall within a range in which the drug produces a therapeutic effect or desired outcome. The safety and effectiveness of prescription drugs in the U.S. is regulated by the federal Prescription Drug Marketing Act of 1987. 97. Legal Concerns Legal regulations, standards, and legislation Controls in the U.S. Testing (animals studies and clinical patient trials) Legislative control 98. Legal Concerns Legal regulations, standards, and legislation Truth in labeling Why might truth in labeling be important? 99. Legal Concerns Legal regulations, standards, and legislation Narcotics Harrison Narcotic Act, 1914 Comprehensive Drug Abuse Prevention and Control Act, 1970 100. Schedule of Controlled Drugs Category Examples Schedule I No recognized medical use; high abuse potential Opiates (heroin), hallucinogens (LSD), depressants (methaqualone) Schedule II Written prescriptions required; no telephone renewals Opiates (codeine, morphine, meperidine), stimulants (amphetamines), depressants Schedule III Prescriptions rewritten after six months or five refills Opiates (codeine >> Risk Procedure/treatment or diagnostic test/assessment should be performed/administered Table 15-7 119. Classes of Recommendations Most previous classes retained with better clarifications and descriptions. Class Indeterminate recommendations, which were used in 2005, are not included in the 2010 AHA Guidelines for CPR and ECC. The elimination of the term Class Indeterminate is consistent with the ACCFAHA Classes of Recommendation. When the AHA writing groups felt that the evidence was insufficient to offer a recommendation either for or against the use of a drug or intervention, no recommendation was given. 120. Levels of Evidence 121. KEY POINT: A recommendation with Level of Evidence B or C does not imply that the recommendation is weak. Many important clinical questions addressed in the guidelines do not lend themselves to clinical trials. Even though randomized trials are not available, there may be a very clear clinical consensus that a particular test or therapy is useful or effective. -2010 AHA ECC Guidelines Circulation 2010;122;S657-S664 122. Patient Medication Rights 123. Patient Medication Rights What are the six rights of patient medication administration that ensure safe, proper, and effective administration? 124. Patient Medication Rights 1. Right patient 2. Right medication 3. Right dose 4. Right route 5. Right time 6. Right documentation 125. Street Smart Medic Tip Be Very Careful with multiple patients, Mutiple providers, and Multiple Drugs The complexity of ANY situation increases the chance of a critical error in medication administration. In otherwords: KEEP YOUR SH*T TIGHT! Street Smart Medic Tip Be Very Careful with multiple patients, Multiple providers, and Multiple Drugs The complexity of ANY situation increases the chance of a critical error in medication administration. In other words: KEEP YOUR SH*T TIGHT! 126. Additional stuff you HAVE to know 127. What Paramedics Need to Know About Drugs Comprehensive drug list based on protocol Be familiar with AHA Guidelines for treating cardiac patients Know local protocol and drugs used in your region 128. Some thoughts on protocols 129. Pediatric Dosages Know the pediatric doses, adult doses, and all approved routes for administration 130. Street Smart Medic: Before giving any drug, several actions must performed: Oxygen and monitor should be started as appropriate Establish IV access with appropriate fluids started 131. Need to Know Components of a drug profile Names Classification Mechanism of action Indications Pharmacokinetics 132. What Paramedics Need to Know About Drugs Components of a drug profile Side effects/adverse reactions Contraindications Dosage How supplied Special considerations 133. Need to Know Special considerations in drug therapy Pediatric patients Geriatric patients Pregnant and lactating patients 134. Need to Know Use care administering medications Follow the medication order 135. What Paramedics Need to Know About Drugs Preparation involves selecting the appropriate sized needle and syringe No compensation for dead space is necessary when drawing up medications 136. What Paramedics Need to Know About Drugs Use different needles when reconstituting medication to be drawn up Use caution when mixing drugs in one syringe ALWAYS use sterile technique 137. Need to Know Medical control As a paramedic, you operate under the licensure of a medical director who is responsible for all of your actions The medical director determines which drugs you will administer and the routes by which they are given 138. Need to Know Reduce the potential for contamination Identify allergies prior to contacting hospital Obtain vital signs Obtain and confirm/repeat order Write the order and the time 139. Need to Know Select the proper medication Inspect the medication Confirm the order and medication Six rights of administration Record drug, dose, volume, route, and time, and obtain vital signs and effects 140. What Paramedics Need to Know About Drugs Storage and handling considerations USP28-NF23, PF30 (6), p. 2118 Storage of Drugs in Emergency Medical Services (EMS) Vehicles Narcotics and controlled substances should be secured according to local protocols 141. Need to Know Important pharmacological terminology What is antagonism? What is cumulative action? What is potentiation? What is synergism? 142. Need to Know Important pharmacological terminology Contraindications Hypersensitivity Idiosyncrasy Side effects Untoward effects 143. Need to Know Important pharmacological terminology Bolus Indication Therapeutic action Tolerance 144. Need to Know Important pharmacological terminology Depressant Habituation Refractory Stimulant 145. Administration Procedures 146. Preparation Before starting each shift, make sure all medications are Stocked in the proper amount Not expired In good condition Stored properly 147. Preparation Make sure you have adequate supplies to administer them Including syringes, needles, or needleless systems 148. Narcotic Drugs Follow local, state, and federal regulations when it comes to usage and storage 149. Administration Procedures Premedication procedures Obtain a complete SAMPLE history Obtain a full set of vital signs Complete a detailed exam Contact medical control for authorization 150. Consider the whole patient Complete a thorough assessment Look for medication bottles and herbal preparations Determine if the patient has been compliant with his or her medication Consider the medications the patient already has on board before you give any more. 151. Get Good Data Get a FULL set of RELIABLE vitals before you administer a medication Be Prepared for adverse reactions Know your situation 152. Administration Procedures Prior to administration Make sure you have all necessary equipment 153. Medical Asepsis During Medication Administration Medical asepsis is keeping the environment free of pathogens Several ways to keep the environment clean include: Sterilization Medically clean Disinfectants Antiseptics 154. Disposal of Contaminated Material Use sharps container to dispose of anything capable of piercing the skin Dispose of all contaminated material in the proper biohazard container 155. Administration Procedures Post-medication procedures Document Obtain a full set of vital signs Complete a detailed exam Ongoing assessment 156. Summary 157. Summary In order to deliver exceptional patient care, the paramedic must have a basic understanding of the responsibilities and scope of management prior to administration of any drug 158. The END