Paramedic Medication Administration PDF

Introduction Medication administration is a defining element of paramedic clinical practice. When given appropriately, medications have the unique ability to correct or decrease the severity of an illness or injury, treat many life-threatening conditions, and substantially reduce patient discomfort....

Introduction Medication administration is a defining element of paramedic clinical practice. When given appropriately, medications have the unique ability to correct or decrease the severity of an illness or injury, treat many life-threatening conditions, and substantially reduce patient discomfort. Conversely, if you administer the incorrect medication, use the incorrect route, select an inappropriate dose, or fail to follow the correct technique for administration, severe and often life-threatening consequences are possible in many situations. This chapter will assist you in minimizing the risks associated with medication administration while providing patients with a large variety of benefits available from pharmacologic interventions. Throughout this chapter, the terms medications and drugs are used interchangeably. When commercial medications, illicit drugs, and other chemicals enter the human body, they may share common characteristics and produce similar clinical effects, despite entering the body under vastly different circumstances. Words of Wisdom The terms medication and drug are often used interchangeably but have differing meanings. A medication refers to a substance used to treat an illness or condition. A drug, generally speaking, is any substance that produces a physiologic effect, whether therapeutic or not; when used in a clinical sense, this term is understood to refer to a substance that produces a therapeutic effect when given in the appropriate circumstances and in the appropriate dose. Therefore, every medication is a drug, but not every drug is a medication. Pharmacology is the scientific study of how various substances interact with or alter the function of living organisms. As a paramedic, you will use the science of pharmacology in various ways, such as when treating patients who already receive medications on an intermittent or long-term basis. You will also encounter patients who are experiencing adverse effects of medications taken at home, so it is crucial to obtain a medication history during the patient assessment. It is also essential to understand pharmacology when administering medications to treat patient symptoms during an EMS response or while treating a patient who has been exposed to a potentially toxic chemical, drug, or medication. Historical Perspective on Medication Administration For centuries, chemicals, primarily derived from plants or animals, have been used to cure disease or relieve symptoms. Early Chinese, Mesopotamian, and Egyptian societies used chemical remedies to treat everything from pain to baldness. Diseases were poorly understood, and natural remedies were directed toward relieving various symptoms rather than ending the disease process itself. Formal scientific study of the effects of medication on the body began to emerge during the late 17th century and into the 18th century. Today, the science of pharmacology has evolved into large-scale commercial pharmaceutical production— a highly profitable and tightly regulated industry. Many unique subspecialties, such as genetic manipulation and toxicology, continue to blur the line between pharmacology, medicine, and a variety of other scientific fields. Although the science of pharmacology has evolved into a sophisticated area of health care, certain medications discovered in ancient times are still in use. The process of medication selection and administration is no longer random or anecdotal as it was in previous centuries Evidence-based guidelines assist clinicians in using pharmacologic interventions across the spectrum of medical specialties Medications now undergo extensive testing and numerous clinical trials before their widespread use is permitted. Yet despite the advanced science of pharmacology, adverse reactions to medications remain commonplace. Medication and Drug Regulation The United States has implemented a comprehensive system of medication and drug regulation. The first significant regulation was enacted in 1906, with the passage of the Pure Food and Drug Act. As its name implies, this act prohibited altering or mislabeling medications. In 1909, the importing of opium was prohibited under the Opium Exclusion Act. The Harrison Narcotics Act, which restricted the use of various opiates and cocaine, became law in 1914. Under the Food, Drug, and Cosmetic Act (1938), the US Food and Drug Administration (FDA) was given authority to enforce rules requiring that new drugs be safe and pure. The FDA remains the federal agency responsible for approving new medications and removing unsafe medications from the market. Approval of a new medication typically takes several years, and only a small fraction of medications submitted to the FDA ultimately receive marketing approval. Occasionally, breakthrough medications for life-threatening conditions may receive preferential expedited consideration or emergency approvals (eg, the COVID-19 vaccines). Notably, many medications, once approved and available commercially, are use.d "off-label" —that is, for a purpose not approved by the FDA, at doses different from the recommended doses, or by a route of administration not approved by the FDA. Off-label use is widespread in health care, but a physician medical director, or paramedic may have an increased risk of liability for ill-advised off-label use of a medication that results in a bad outcome for a patient. Medications should be administered off-label only when they are specifically approved for this use by the service's medical director or by agency/regional protocol. The use of intravenous (V) tranexamic acid in patients who have experienced trauma, discussed later in this chapter, is an example of off-label medication use in EM.S As an EMS provider, you must be familiar with the rules and regulations implemented under the Controlled Substances Act (also known as the Comprehensive Drug Abuse Prevention and Control Act) of 1970. This act classifies certain medications with the potential of abuse into five categories (schedules), with corresponding security, dispensing, and record-keeping requirements Table 13-1. The US Drug Enforcement Agency is responsible for enforcing this act. Classification of Medications Considered Controlled Substances Schedule Description Examples High abuse potential; no recognized medical purpose Heroin, marijuana (cannabis), LSD, peyote High abuse potential; legitimate medical purpose  Opioids: codeine, fentanyl (Sublimaze), hydrocodone, hydromorphone (Dilaudid), morphine Stimulants: amphetamine (Adderall), cocaine, methylphenidate (Ritalin) medications Lower potential for abuse than Schedule Opioids: acetaminophen with codeine (Tylenol with codeine 3) Nonopioids: anabolic steroids, ketamine IV drugs Lower potential for abuse than Schedule III Alprazolam (Xanax), diazepam (Valium), lorazepam (Ativan) Lower potential for abuse than Schedule IV Opioid cough medicines drugs Abbreviation: LSD, lysergic acid diethylamide Schedule medications may not be prescribed, dispensed, used, or administered for medical use, Mariuana, which is Nancy Carolines Emergency Care in the Streets Flipped Classroom, 9... Schedule I medications may not be prescribed, dispensed, used, or administered for medical use. Marijuana, which is sometimes prescribed for medical purposes, remains a controversial Schedule I controlled substance. Various states permit prescription marijuana for specific medical conditions, and some allow both medical and recreational use. YOU are the Paramedic Part 1 The communications center dispatches you and your partner to a skilled nursing facility for an 88-year-old woman reported to have altered mental status. Additional dispatch information advises that the patient has a pulse and is breathing, but has a decreased level of consciousness. 1. What medical conditions would you expect to encounter in a skilled nursing facility or long-term care facility? Paramedics are likely to carry and administer Schedule Il medications such as fentanyl (Sublimaze) and morphine sulfate, and Schedule IV medications such as midazolam (Versed), diazepam (Valium), and lorazepam (Ativan). All Schedule I through V medications require locked storage, detailed record keeping, and controlled wasting procedures. State EMS pharmacy, or law enforcement agencies may impose additional requirements for the security and accountability of these controlled substances. Words of Wisdom Maintaining careful accountability of controlled substances can protect both the paramedic and the EMS organization. Failure to adequately control and waste controlled substances may jeopardize your job, your reputation, and your professional certification or licensure. Sources of Medication Medications can be derived or manufactured from a variety of sources. Ancient societies used medications isolated from the roots, leaves, seeds, fruit, flowers, or bark of certain plants. Animals, particularly animal endocrine systems, are used as the source of other medications. Minerals represent yet another source of many medications used for a wide variety of clinical conditions. Microorganisms such as bacteria, fungi, and mold also are used for the manufacture of medication. Table 13-2 lists sources of many common medications. TABLE 13-2 Sources of Medications Examples Plant Atropine, aspirin, digoxin, morphine Animal Heparin, antivenom, thyroid preparations, insulin Microorganism Streptokinase, numerous antibiotics, dextran Mineral Iron, magnesium sulfate, lithium, phosphorus, calcium Nancy Carolines Emergency Care in the Streets Flipped Classroom, 9... © Jones & Bartlett Learning. Many other medications are either synthetic (made entirely in a laboratory setting) or semisynthetic (made from chemicals derived from plant, animal, or mineral sources that have been chemically modified in a laboratory setting). Genetic engineering is also used to manufacture certain medications that cannot otherwise be obtained from natural sources. Pharmaceutical companies tightly control the concentration, purity, preservatives, and other ingredients present in medications during the manufacturing process. The United States Pharmacopeia-National Formulary ([USP-NF] discussed 72 later) is an excellent source of information regarding the manufacturing details of a particular medication. On the packaging of each medication, you will notice a manufacturing lot number and expiration date. Forms of Medication You will manage and administer medications in various forms. The vast majority of medications administered in EMS practice are sterile injectable solutions. These solutions require careful handling and aseptic technique during administration to avoid contamination with microorganisms or other harmful substances. These solutions are supplied in larger IV bags, vials, and Table 15-3ana occasionally in glass bottles (eg, nitroglycerin and ethanol). Other forms of medication are outlined in TABLE 13-3 Forms of Medication Form Description Examples Capsule Powdered or solid medication enclosed in a dissolvable cylindrical gelatin shelf.l Acetaminophen (Tylenol), ibuprofen (Motrin), diphenhydramine (Benadryl) Tablet Solid medication particles are bound into a shape designed to dissolve or be swallowed. Aspirin (ASA), nitroglycerin SL Powder Small particles of medication designed to be dissolved or mixed into a solution or liquid Glucagon, vecuronium (Norcuron) Droplet Sterile solution or nonsterile liquid intended for direct administration into the nose or ear Phenylephrine (Neo-Synephrine, Afrin), tetracaine, naloxone (Narcan) Parenteral solution Sterile solution for direct injection into a body cavity, tissue, or organ Fentanyl (Sublimaze), epinephrine Skin preparation Gel, ointment, or paste substance designed to permit transdermal (through the skin) absorption Nitroglycerin paste, fentanyl (Sublimaze) patch Suppository Medication in a wax-like material that dissolves in the rectum or other body cavity Promethazine (Phenergan), acetaminophen (Tylenol) Liquid Medication dissolved or suspended in liquid intended for oral consumption Infant acetaminophen (Tylenol), cough syrup Inhaler/spray Medication in gas or fine mist form intended for inhalation and absorption through the lung, airway, or oral tissues Albuterol (Ventolin), nitroglycerin spray Abbreviations: ASA, acetylsalicylic acid; SL, sublingual Medication Management for Paramedics Medication Names Every medication in the United States is given three distinct names: a chemical name, a generic or nonproprietary name, and a brand or proprietary name. During their initial development, medications are given a chemical name, which is often long and difficult to pronounce and may contain specific letters or numbers that indicate the medication's chemical composition. The chemical name is rarely used in clinical practice. Sodium bicarbonate, potassium chloride, and some other medications are among the few exceptions in which the chemical name is used in clinical practice. Most medication reference sources used by paramedics do not publish the chemical name or structure of a medication Every medication also receives a nonproprietary, or generic, name. The manufacturer proposes the generic name, which must be approved by the US Adopted Names Council and the World Health Organization. The generic name is regulated 730 internationally to promote consistency and avoid duplication in drug names. Generic names typically include a "stem" that links them to other medications in the same drug class (the grouping to which a medication belongs). Often the stem is found at the end of the name, but it may also appear at the beginning or within the drug name. For example, many benzodiazepine medications, such as midazolam, diazepam, and lorazepam, have the stem "am." The stem "pril" signifies that medication is a member of the angiotensin-converting enzyme (ACE) inhibitor medication class, such as enalapril (Vasotec), captopril (Capoten), and lisinopril (Prinivil, Zestril). Several other examples of stems exist. In addition to knowing that stems provide information about the class of drugs, you need to know the specific names of and indications for all drugs that you administer. SAFETY Do not rely solely on the stem when attempting to determine the medication class to which a drug belongs, because different classes might have the same stem. The names for tricyclic antidepressants, such as amitriptyline (Elavil) and desipramine (Norpramin), have the same stem as the names for some selective serotonin reuptake inhibitors (SSRIs), such as fluoxetine (Prozac) and paroxetine (Paxil). An overdose of a tricyclic antidepressant is often life threatening, whereas an overdose of an SSRI does not typically pose the same risk. The final type of medication name is the brand name, which is chosen by the manufacturer and approved by the FDA. The brand name does not have the same functional requirements as the generic name, but it must meet certain minimum criteria set by the FDA. Brand names are often selected for marketing purposes. Creative examples are sometimes linked to a particular condition. Metoprolol, a beta-adrenergic blocking agent, has the brand name Lopressor, which may be a subtle reference to lowering pressure (of the blood). Oseltamivir has the brand name Tamiflu and is used to treat influenza. The three distinct types of medication names can be illustrated with an example. The following medication is commonly administered by paramedics: Chemical name: 4-chloro-N-furfuryl-5-sulfamoyl anthranilic acid Generic name: furosemide Brand name: Lasix Many reference sources now use "tall man" lettering to print the names of certain medications. This approach is intended to avoid confusion of medications with similarly spelled names. The capitalized letters highlight a portion of the name in medications with similar names. Examples include DOBUTamine and DOPamine, and diphenhydrAMINE and dimenhyDRINATE SAFETY Many medication names look and sound the same. Minimize the risk of medication errors by double-checking the medication container label every time you are preparing to administer a medication. Concentrations and packaging may change unexpectedly. Medication Reference Sources A vast array of medication reference sources are available to assist you in clinical practice. When selecting a reference source to use or purchase, consider a variety of factors, including the reliability of the reference source; whether the source is printed, electronic, or both; the depth of information needed or provided; accessibility; cost; availability of updates; and size of materials used (if a printed product). Medication information is typically compiled in a format called a medication monograph or medication profile. The details may vary dramatically between reference sources, but the basic structure remains consistent. Table 13-4 highlights common components of medication profiles TABLE 13-4 Components of Medication Profiles Component Description Medication names Sources typically include both the brand name and the generic name. Print sources often alphabetize entries by generic name. Electronic sources can typically be searched by either brand name or generic name. Category or class of medication The grouping to which a medication belongs. Medications are grouped according to their characteristics, traits, or primary components. Use/indication A sign, symptom, or condition that would potentially benefit from a particular medication; the reason for giving a medication. Mechanism of action (pharmacodynamics) The way in which a medication produces the intended response. Pregnancy risk factor A scale indicating the likelihood of potential harm to the fetus if the medication is administered to a pregnant patient. Contraindications Any condition, but especially a disease, that is known to render some particular line of treatment improper or undesirable. Available forms (how supplied) The manner in which the manufacturer packages the medication for distribution and sale. Typical methods of packaging are prefilled syringes, vials, or ampules. Dosage (often differentiated based on age or indication) The typical or average volume or dose of medication that is to be administered to the patient and the route by which the medication should be introduced to the patient. Administration and monitoring considerations Any additional information needed to safely administer the medication and any important parameters that should be observed following administration. Potential incompatibilities Problems that may occur when two or more medications are administered together, which could be at the same time, in the same solution, or through the same intravenous tubing or delivery device (nebulizer, syringe, etc). Adverse effects Any abnormal or harmful effects caused by exposure to a chemical. An effect may be classified as adverse if it causes functional or anatomic damage, causes irreversible change in the person's homeostasis, or increases the person's susceptibility to other chemical or biological stress. Pharmacokinetics The medication's effects on the body, as described by the following terms: Onset. The estimated amount of time it will take for the medication to enter the body/system and begin to take effect Peak. The estimated amount of time it will take for the medication to have its greatest effect on the patient/system. Duration (of action). The estimated amount of time that the medication will have an effect on the patient/system. Special Populations Pediatric and older patients often have slower medication absorption and elimination times, necessitating modification of the doses of many drugs administered to these patients. Pregnant patients are limited in terms of the medications they can take because of the potential risk to the fetus. The USP-NF and the Prescriber's Digital Reference (PDR, formerly called the Physicians' Desk Reference) provide a wealth of reliable, detailed information about thousands of medications. The information includes graphic diagrams of the chemical structure and other specific chemical properties of the medications. Electronic versions of these resources, such as those available through smartphone apps, have improved their accessibility in the field. The earlier printed forms were impractical to use in prehospital settings because of their size and amount of information. Despite the improved form factor, many of the details in these sources are not needed in prehospital settings, making it difficult for paramedics to locate needed information rapidly. The electronic versions of the USP-NF and PDR may be helpful to EMS educators and administrators in developing agency-specific medication protocols or creating training materials. Manufacturers provide written materials with every package of medication distributed. These "package inserts" are written by the manufacturers and approved by the FDA. Such package inserts include information on dosing, route of administration, contraindications, adverse effects, and various other characteristics of a particular medication. Hospital pharmacies often compile medication information into formularies that are specific to the information needs of the specific hospital. The hospital formulary typically includes much of the same information that is included in the medication package insert, USP-NF, or PDR, but it is tailored to the needs of prescribers in the hospital. Paramedics in hospital-based or hospital-affiliated EMS systems may have access to the hospital formulary. You have many other choices for commercially published medication information references. Some resources are specifically geared toward prehospital or critical care transport providers, emphasizing medication selection, dosing, and administration for patient conditions encountered in these settings. Other references focus exclusively on IV medications or emphasize only information needed during hands-on patient care. As mentioned, advancements in portable electronic devices and smartphones mean that many medication references are now accessible electronically, making an entire library of information available within the limited confines of the emergency vehicle. State EMS agencies and individual fire and EMS organizations frequently develop specific protocols or medication formularies, which compile information on approved medications given by paramedics in a particular setting of Wisdom. Find a pocket-size medication reference source (print or electronic, such as a smartphone app) that works well for you, and always keep it, along with a copy of your regional protocols, with you while on duty. AHA Classification of Recommendations and Level of Evidence In most EMS settings, you will follow guidelines established and distributed by the American Heart Association (AHA). These guidelines may be referenced directly, or they may be incorporated into more extensive department or agency policies or protocols. The medications and interventions listed within the AHA guidelines have varying degrees of support from reliable scientific evidence. Chapter 1, _EMS Systems, discusses the distinction and relationship between a class and a level of evidence. You can generally infer the level of evidence by the assigned class for a proposed intervention. To provide greater clarity to healthcare providers regarding the level of evidence, the AHA uses the following system to describe the relative importance of certain medications or interventions: Class / indicates that strong evidence supports the use of the procedure/medication, the benefit is greater than the risk, and the intervention should be performed or administered Class Ila indicates moderate evidence that the benefit is greater than the risk, the intervention is reasonable, and the intervention may be useful. Class Ilb indicates weak evidence that the benefit is greater than the risk; the intervention may be considered Class Ill no benefit indicates the evidence is weak, the benefit equals the risk, and the intervention should not be performed/administered Class Ill harm indicates there is strong evidence that the risk is greater than the benefit, and the intervention should not be performed/administered. Medication Storage Medication storage is an essential consideration for paramedics. The uncontrolled prehospital environment is a difficult place to maintain the safety and integrity of medication packages. Medications must be kept in a location that provides adequate protection for medication supplies, yet is convenient enough to allow quick access in emergency situations. A fundamental concern regarding medication storage is the integrity of the medication container. Medication should be stored in a manner that prevents physical damage to the medication vial, ampule, solution, or tablets. It is often necessary to remove most of the packaging provided by the manufacturer, leaving only the medication container in the vehicle or response bag. Because drug boxes or bags may be dropped accidentally during a call, medication containers should be placed in protective bins or surrounded by enough padding to prevent damage to them during a response or while performing patient care at the scene. Organize medication containers in a manner that facilitates quick, accurate identification of the medication during emergency situations. The needs of individual EMS organizations dictate the type and quantity of medications that are available on a particular response vehicle or in a provider's bag. Carrying excessive medication quantities may make storage difficult or cause unnecessary waste due to expiration. Conversely, having insufficient quantities on hand may undermine patient care or necessitate frequent restocking. State EMS regulations require that EMS agencies have policies in place that define appropriate storage, maintenance, and replacement of medications and IV fluids. Direct sunlight, extremes of heat and cold, and physical damage to medication containers can hasten the degradation of many medications, making them ineffective or unsafe for use. Many EMS agencies use medication heaters, coolers, or refrigerators in their emergency vehicles to control the temperatures at which medications are stored and ensure the safety and integrity of the medications they carry. Words of Wisdom Take steps to ensure medications are stored at the proper temperature. Paramedics working in locations subject to extreme temperatures may be administering medications that have reduced effectiveness due to the environment in which they are stored.? Medication Security Controlled substances (as described in Table 13-1) require additional security, record-keeping, and disposal precautions. These medications must be kept in locked storage cabinets or continuously held by an on-duty EMS provider responsible for administration. Disposal of partially used or damaged medication containers requires verification by a witness or return of the damaged or unused portion to the department responsible for dispensing the medication EMS agencies and individual paramedics are jointly responsible for adhering to all federal, state, and local regulations regarding the security and accountability of controlled substances. These regulations vary slightly from region to region. In general, every last milliliter or milligram of a controlled substance needs to be documented from ordering to receipt by the EMS agency to administration by the EMS provider (or discarded as waste). The particular forms and procedures may vary from place to place, but the standard for accountability remains constant. Controlled substances are often the target of tampering or diversion Inspect medication vials, ampules, and the like for subtle signs of tampering, which may be as small as a pinhole. Suspect tampering in situations in which appropriate doses of analgesic or sedative medications seem ineffective, especially when patient tolerance is unlikely. The Physiology of Pharmacology The purpose of medications is to produce a desired effect in the body, usually in response to a particular illness, injury, or medical condition, but occasionally to prevent a specific harmful situation. As a medication is administered, it begins to alter a function or process within the body. This action is known as pharmacodynamics. Any medication capable of beneficial clinical effects can cause toxic effects when given at an excessive dose. Toxic effects may also occur if a medication is given by an incorrect route or when a delivery device, such as an IV catheter or intraosseous (10) needle, malfunctions. In other cases, medications may become ineffective when given at an inadequate dose or through the incorrect route. Even in the absence of error, many factors related to the patient, the patient's condition, and the particular medication may cause toxicity or adverse effects. The human body simultaneously begins the process of absorption, distribution, possibly biotransformation, and, ultimately, elimination of a medication or chemical following administration. The body's action on a medication is 734 known as pharmacokinetics. You must always consider the principles of pharmacodynamics and pharmacokinetics when deciding whether to administer a particular medication. Principles of Pharmacodynamics Research has demonstrated the presence of receptor sites in proteins connected to cells throughout the body. Various receptors are activated by endogenous chemicals, those occurring naturally within the body, and by the presence of medications and chemicals absorbed into the body. Activation of these receptors produces a specific response by individual cells, tissues, organs, and, ultimately, body systems. When a medication binds with a receptor site, one of four possible actions will occur: 1. Channels permitting the passage of ions (charged particles) in cell walls are opened or closed. 2. A biochemical messenger becomes activated, initiating other chemical reactions within the cell. 3. A normal cell function is prevented. 4. A normal or abnormal function of the cell begins. For purposes of this chapter, exogenous (from outside the body) chemicals will be referred to as medications, even though exposure to chemicals in the environment can cause effects similar to those of medications, including adverse effects. Clandestine methamphetamine laboratories are an excellent example of environmental exposure to a chemical. Law enforcement officers and other emergency responders may experience accidental inhalation or dermal exposure to methamphetamines during an emergency response and demonstrate clinical effects identical to those of people who intentionally abuse these substances. In another example, toddlers who accidentally ingest certain mouse poisons will exhibit clinical effects identical to those experienced following the therapeutic administration of warfarin (Coumadin). The exposure is different from normal therapeutic administration in each of these instances, yet the clinical effects are identical. Later sections of this chapter will discuss specific medications and chemicals used by paramedics and introduce the properties of various classes of medications pertinent to prehospital care. Chapter 28, Toxicology, discusses the adverse properties of commonly abused drugs. Functionally, the distinction between the terms therapeutic medications, exogenous chemicals, and illicit drugs is largely irrelevant. These terms reflect substances that follow similar (and often predictable) patterns when interacting with the body. Medications are developed to reach and bind with particular receptor sites of target cells. Newer medications are designed to target only specific receptor sites on certain cells to minimize their adverse effects. In contrast, many older medications, including those used by paramedics, affect cells and tissues unrelated to the condition being treated, causing adverse effects throughout the body. Two types of medications or chemicals directly affect cellular activity by binding with receptor sites on individual cells. Agonist medications initiate or alter cellular activity by attaching to receptor sites, prompting a cell response. Antagonist medications prevent endogenous or exogenous agonist chemicals from reaching cell receptor sites and initiating or altering a particular cellular activity Figure 13-1. Specific notable agonist-antagonist pairs are discussed at various points later in this chapter. For example, opioids such as morphine sulfate and fentanyl are agonist chemicals that cause analgesia and respiratory depression. The effects of these chemicals can be reversed by the opioid antagonist naloxone (Narcan).Agonist Medications The dose of a particular medication, the route of administration, and many other factors determine the concentration of a medication present at target cell receptor sites. Affinity is the ability of a medication to bind with a particular receptor site. Together, medication concentration and affinity determine the number of receptor sites bound by that medication. As noted earlier, agonist medications bind with receptor sites, initiating or altering an action by the cell. A certain minimum concentration of the agonist medication must be present for cellular activity to be initiated or altered. As the concentration of the medication increases and crosses the threshold level, initiation or alteration of cellular activity begins. Increasing concentrations of medication cause increased effects until all receptor sites become occupied or the maximum capability of the cell is reached. The concentration of the medication required to initiate a 735 cellular response is known as the medication's potency. As the potency of a medication increases, the concentration or dose required for a particular cellular response decreases. Conversely, a higher concentration is required when the potency of a medication is low. The ability to initiate or alter cell activity in a therapeutic or desired manner is referred to as efficacy. Once all the cellular receptor sites become bound with the agonist medication, cellular activity plateaus and no increase or further change in activity is possible. At this point, the effect of the medication has peaked, and additional doses or higher concentrations of the medication will not cause additional cellular action. The dose-response curve illustrates the relationship between medication dose (or concentration) and efficacy. The relative potency of two different medications causing the same effect can be demonstrated by comparing their dose-response curves. The threshold dose is lower for medications with a higher potency Figure 13-2.Antagonist Medications As mentioned earlier, antagonist medications bind with receptor sites to prevent a cellular response to agonist chemicals. Antagonists may be used to inhibit normal cellülar activation by naturally occurring agonist chemicals within the body. Antagonist medications may also be used to treat the harmful agonist effects of exogenous medications or chemicals, possibly following an overdose or a toxic exposure. Antagonists may be competitive or noncompetitive. Competitive antagonists temporarily bind with cellular receptor sites, displacing agonist chemicals. The efficacy of a competitive antagonist medication is directly related to its concentration near the receptor sites. As the concentration of a competitive antagonist increases near the receptor sites, it can prevent additional agonist chemicals from reaching the receptor, thereby decreasing cellular action. This effect can apply to a large quantity of one particular agonist chemical or the presence of multiple chemicals with similar agonist effects. As the concentration of the competitive antagonist decreases (due to the elimination of the drug or substance, such as through the kidneys) or when the concentration of agonist chemicals increases, more agonist chemicals can bind with receptor sites and continue or resume cellular activation. The efficacy of a competitive antagonist medication is also related to the strength of its affinity (ability to bind at a receptor site) compared with the affinity of the agonist chemicals present. Competitive antagonist medications with a lower affinity require a higher concentration to be effective. Noncompetitive antagonists permanently bind with receptor sites and prevent activation by agonist chemicals. Effects of noncompetitive antagonist medications continue until new receptor sites or new cells are created, which may be a long time after the last dose of antagonist medication is given. Ketamine (discussed later) is a noncompetitive antagonist of the agonist glutamate on N-methyl- D-aspartate receptors in the central nervous system. (CNS). The effects of ketamine last for only 10 to 15 minutes. Aspirin (also discussed later) is a noncompetitive antagonist that binds to the enzyme cyclooxygenase, causing antiplatelet effects that last up to 10 days when platelets are regenerated. Even increased doses of agonist chemicals will not overcome the presence of noncompetitive antagonist chemicals on cellular receptor sites. Partial Agonist Chemicals It is also possible to have a partial agonist chemical attached to cellular receptor sites. Partial agonists bind to the receptor site but do not initiate as much cellular activity or change as other agonists. In essence, partial agonists effectively lower the efficacy of other agonist chemicals that may be present in the cells. Buprenorphine (Buprenex, Subutex) is a partial agonist medication used for both analgesia and the treatment of opioid addiction. Buprenorphine has a high affinity for the mü (p) opioid receptors (described in Table 13-10), and its binding to them prevents agon.sm by other opioid chemicals. Although buprenorphine provides some degree of agonism, causing analgesia and euphoria, it has a "ceiling effect" that allows only partial activation of the opioid receptors, minimizing the risk of toxicity and physical dependence. The maximum effects possible from buprenorphine are much weaker than the effects from other opioid chemicals. Alternative Mechanisms of Drug Action Some medications can alter cell, tissue, organ, and system function in the body without directly interacting with receptors on individual cells. For example, medications may be engineered to target other sites throughout the body, including microorganisms, lipids, water, and exogenous toxic substances. Antimicrobials, such as antibiotics and antifungals, may be designed to target specific substances present in the cell wälls of a particular bacterium or füngus. Öther medications, known as chelating agents, bind with heavy metals such as lead, mercury, and arsenic in the body and create a compound that can be eliminäted. Sodium bicarbonate (discussed in detail later in this chapter), a medication used for a wide variety of medical conditions, breaks down after administration, producing bicarbonate ions. Bicarbonate ions can bind with excess hydrogen ions, raising the pH and decreasing the acidity of various body fluids. Mannitol (Osmitrol) is a diuretic medication, designed to distribute into water in the body, creating osmotic changes that alter the distribution of flüids and electrölytes. The resulting diuretic effect draws excess water from certain bodyMannitol (Osmitrol) is a diuretic medication, designed to distribute into water in the body, creating osmotic changes that alter the distribution of fluids and electrolytes. The resulting diuretic effect draws excess water from certain body tissues, including the brain and eyes, while enhäncing urine excretion. Plasma expanders and bulk laxatives target water in the body and älter the distribution of various body flüids. Electrolyte-based medications such as magnesium, potassium, and calcium change the concentration and distribution of ions in cells and fluids throughout the body, affecting many cell activities. An alteration in the concentration of certain electrolytes at the cellular level affects the ability of various cells to function. Alterations of cell function occur without chemicals directly binding to cell receptor sites. Factors Affecting Response to Medications Several factors determine how a particular medication will affect a patient. These factors may influence the choice of medication, dose, route, timing, manner of administration, and monitoring necessary after a patient receives a medication. Even weight-based medication dosing, which is common in the prehospital setting, produces profound differences in how a medication affects an individual patient because of the factors described in the following sections. Age The distribution, metabolism, and elimination of medications continue to change throughout the human life span. Therefore, the responses of ölder adült and pediatric patients to various medications can be much different from the responses seen in adolescents and adults. You may encounter unusual situations that require you to consult with online medical control to adjust the dose of medication for infants, children, and older patients to obtain the desired response. Medications become distributed into three primary types of body substances (water, lipids or fat, and protein) following administration. The percentage of body fat is lowest in preterm infants, increases significantly in toddlers, decreases through adolescence, and increases in adults, including older adults. The percentage of body water is highest in newborns and steadily decreases throughout the life span. The percentage of body protein varies throughout the life span, generally peaking in preteens, adolescents, and adults. Infants and older adults have the lowest percentage of body protein. If a medication is water-solüble, higher weight-based doses must be administered to infants (who have a higher percentage of body water) than to adults and older adults. Fat- and lipid-soluble medications require higher weight-based doses in older adults because of their higher body fat percentage and increased fat distribution. When treating pediatric or older patients with altered percentages of body water, fat or lipids, and protein, consider performing careful titration of the medication selected rather than simply administering a weight-based bolus. Water-soluble and lipid-soluble medications may require increased initial doses to overcome the dilution that inevitably occurs with their widespread distribution in the body. Older adult patients, for example, generally have a lower percentage of body water. Therefore, water-soluble medications, such as digoxin, will have higher serum levels in older patients than in other patients who weigh the same and are given the same dose. Older adults have less body water for the digoxin to spread into, which leads to a higher concentration of this medication in the body water that is present, particularly in the blood (serum). Older adult patients also generally have a higher percentage of body fat. Lipid-soluble medications such as diazepam initially produce much lower serum levels for a given dose, but they take much longer for the body to eliminate, dramatically prolonging their effects. Without careful monitoring, it can be easy to exceed therapeutic serum levels when administering repeated doses, causing adverse or toxic effects that may persist for hours to days. Information on the solubility of a medication is typically included in its reference materials. Alteration of metabolism and elimination in pediatric and older patients may prolong the effects of medications or result in higher medication concentrations in various tissues. Medication metabolism in the liver is affected by the cytochrome P-450 system (discussed later in this chapter). This system works differently on different types of medications, is extremely variable in infants and children, and shows a functional decline in older adults. Hepatic metabolism is also generally impaired in older adults due to decreases in blood flow to the liver. A decline in liver or kidney function, due to aging or another cause, requires a decrease in the dosage of many medications because their patients at extremes of age are disproportionately susceptible to paradoxical medication reactions- that is, clinical effects opposite to the intended effects of the medication. For example, sedative medications can produce profound excitement or agitation rather than sedation. Barbiturates can cause unexpected excitement or agitation in older patients. Promethazine (Phenergan), diphenhydramine (Benadryl), chloral hydrate, and various benzodiazepines, such as midazolam, can cause paradoxical excitement or agitation in children. Paradoxical reactions frequently complicate an already delicate clinical situation when patients who need sedation become even more excited, agitated, or combative. Many medications used in prehospital care and critical care transport are administered using weight-based dosing. To calculate the recommended dose for the individual patient, a quantity of medication (usually grams, milligrams, micrograms, or milliliters) is multiplied by the patient's weight in kilograms. This method of medication dosing has both advantages and limitations. The major advantage of this method is that the amount of medication administered is proportional to the patient's size. Medication manufacturers and clinicians have already calculated factors affecting absorption, distribution, metabolism, rates of elimination, and desired quantity present at target cells or tissues when giving a particular medication at a weight-bäsed dose. You can use the weight-based formula to determine the appropriate medication dose for patients ranging from preterm neonates to large adults. Limitations associated with this method include the fact that the patient's weight in kilograms is needed to calculate a weight-based medication dose. A patient's weight must be estimated in emergency situations and, often, converted from pounds to kilograms. Even in controlled settings, healthcare providers might have difficulty accurately estimating patient weights. One study revealed that a significant portion of healthcare providers' estimates of patient weight were off by more than 10% to 15%. Patients generally estimate their own weight more accurately than do healthcare providers. An inaccurate estimate of a patient's weight, depending on the degree of error, could result in the administration of an incorrect dose of medication. Another limitation of weight-based dosing is the risk that multiplication of numbers in the formula during a stressful situation or at an uncontrolled scene may lead to dosing errors. Using a calculator or a preprinted medication dose chart when administering weight-based medications can help reduce these kinds of errors. Special Populations Before administering any medication to a pediatric patient, ask the parents whether the child has had a previous reaction, such as a paradoxical reaction. The weight-based method of dose calculation also does not consider the various alterations in distribution, metabolism, and elimination discussed earlier. Standard data regarding the percentages of body water, fat, and protein at various ages become less reliable as obesity and malnutrition affect patients. Weight-based medication doses can be calculated by using the patient's actual body weight or ideal body weight. For example, lidocaine, an antidysrhythmic medication, is administered based on a patient's actual body weight. In contrast, the cardiac medication digoxin is given based on a patient's ideal body weight. Unfortunately, many reference sources do not provide guidance about whether the patient's actual or ideal body weight should be used for medication dose calculations. The formulas for ideal body weight in adults are as follows: For men: Ideal weight (kg) = 50 + (2.3 times patient's height in inches over 5 feet) For women: Ideal weight (kg) = 45.5 + (2.3 times patient's height in inches over 5 feet) For example, the ideal weight for a 6-foot-tall man is 77.6 kg [50 + (23 x 12)], and the ideal weight for a 5-foot, 5-inchEnvironment Both hyperthermia and hypothermia can affect medication absorption, metabolism, and efficacy. Fever causes tachycardia that may increase hepatic blood flow, theoretically increasing the initial metabolism of drugs in the liver and reducing the amount of drug returned to circulation by the liver. Fever also suppresses the function of the 739 cytochrome P-450 system in the liver, which ultimately decreases the rate of metabolism of certain classes of medications. In consequence, individual patient responses may vary from the expected response. Hypothermia is known to impair the effectiveness of medications used in traditional advanced cardiac life support. (ACLS): The 2020 AHA ACLS guidelines state that it may be reasonable to consider the administration of epinephrine Strategies dia arrest caused by accidental hypothermia per the standard ACS algorithm concurrent with rewarming Genetic Factors Be extremely careful when deciding whether to administer medications to patients with specific genetic disorders. Primary pulmonary hypertension, sickle cell disease, and glucose-6-phosphate dehydrogenase deficiency are some notable conditions that require special consideration, and their presence in a patient may rule out the use of certain medications frensatin minored by parameters essence medications. Salicylate medications such as acne acute decompensation when they receive vasopressor medications. Medications such as (acetylsalicylic acid) May precipitate hemolysis (destruction of red blood cells [RBCs] by disruption of the cell membrane) in patients with glucose-6-phosphate dehydrogenase deficiency. Patients with sickle cell disease require adequate hydration and intravascular fluid volume. Medications that cause diuresis, such as furosemide (Lasix), or vasoconstriction, such as epinephrine or dopamine, may cause or worsen potentially fatal complications of sickle cell disease. Many other genetically linked conditions require careful consideration when administering medications in the prehospital setting. Subtle genetic variations among individuals may trigger significantly different responses to the same medication. The effects of ACE inhibitors, beta-2 agonists, antipsychotic medications, warfarin, aspirin, and glycoprotein lib/illa inhibitors are all linked to the actions of particular genes. Variations in the expression of these linked genes will cause differing responses to each of these medications or medication groups (along with many others). The profound impact of genetic variations on medication response has prompted the development of a vast array of genetic screening tests specific to certain disease states or medications. Street Smarts Patients with genetic disorders and their family members are often excellent sources of information specific to the disorder. You should take advantage of the knowledge of patients and family members about genetic conditions; admitting a lack of knowledge about an unusual genetic condition and treating patients and families as experts on the genetic condition can help build their confidence in you. 米 Pregnancy Pregnancy causes an array of physiologic changes in the body, which in turn can significantly affect medication decisions. Cardiac output and intravascular volume increase dramatically during pregnancy, with each rising by about 40% above prepregnancy levels. The hematocrit (ie, the percentage of RBs in the intravascular space) decreases in response to an increase in overall blood plasma volume. Respiratory tidal volume and minute volumes increase, while the inspiratory and expiratory reserve volümes decrease. Gastrointestinal (Gl) motility decreases as pregnancy progresses. Renal blood flow and urinary elimination increase, roughly in proportion to cardiac output, and urinary elimination increases, roughly in proportion to cardiac output and intravascular volume. Möst endocrine glands undergo some degree of change during pregnancy, leading to emotional instability, altered glucose metabolism, thyroid-generated tachycardia, and other conditions. Each of these changes can affect the absorption, distribution, or elimination of medications during pregnancy. The stress imposed on the body during pregnancy from these changes can also exäcerbate an underlying disease process, potentially threatening the life or health of the patient and fetus. In addition to accounting for alterations in the woman's body during pregnancy, you must consider potential harmful effects on the developing fetus when administering medication to a pregnant patient. To determine whether a specific medication is safe for a pregnant woman and the developing fetus, paramedics should consult the medication's label (ie, the package insert), which 740 provides FDA-approved information on the following topics®: Pregnancy, including labor and delivery Pregnancy exposure registry Risk Summary Clinical considerations Data Lactation, including nursing mothers Risk Summary Clinical considerations Data Reproductive potential effects, for both females and males Pregnancy testing Contraception Infertility As of 2018, this drug label format officially replaced the FDA's previous risk letter categories (A, B, C, D, and X), which were criticized for providing misleading or insufficient information. In general, medications and interventions that protect the life and health of the mother are usually in the best interest of the dependent fetus. Most medications given by paramedics do not pose an unacceptable risk to a fetus. Even so, you must consider pregnancy risk implications whenever you are contemplating medication administration to a potentially pregnant patient. Avoid medications known to cause harm to the fetus in all but the most extreme, life-threatening situations for the mother. In situations involving a direct threat to the patient's life, it is often necessary to administer a higher-risk medication to preserve the life of the mother, regardless of the risk to the unborn child. Online medical contröl physicians can often provide guidance in these difficult situations. Most commercial reference sources provide the FDA pregnancy risk category for each medication. A medication's pregnancy risk category is also listed within its medication monograph. Aspirin and certain benzodiazepines such as diazepam and midazolam are common prehospital medications known to cause fetal harm. special Populations 贝 Treat every female of childbearing age as though she could be pregnant. Psychosocial Factors Be aware of the role of psychosocial factors in the effectiveness of medications when selecting and administering medications. Pain, anxiety, and overall discomfort can vary dramatically among individual patients with the same illness or injury. Unlike measurable vital signs and readily observable clinical findings, patients' perceptions of and responses to discomfort are largely subjective. Psychological, cultural, emotional, and situational factors may influence the amount of discomfort reported by patients in relation to the underlying medical condition, patient positioning, environmental stressors, and the interventions you may perform during treatment. You should be alert to verbal and nonverbal cues when assessing for discomfort and administering medications for anxiety, pain, and sedation. Nonverbal cues may be indicated by changes in vital signs, facial expression, posture and movement changes, altered respiratory patterns, tears or crying, and other behaviors. These cues can provide potentially useful information about patient pain, anxiety, or discomfort but can have different meanings to different people, so your interpretation of the cues should be confirmed with the patient. Medication administration is further complicated by the placebo effect. Numerous studies have demonstrated that patients often experience measurable clinical improvement or have ünexplained adverse effects after receiving a medication with no pharmacologic properties. Placebos were used commonly in 17th- and 18th-century medical practice and their use continued until the early 1900s. Pharmacologically inactive medications continue to be used by healthcare researchers to validate the efficacy or adverse effects of investigational medications by quantifying the placebo effect present in the particular study. The physiölogic mechanism of the placebo effect remains under speculation. Pain relief from a placebo may come from endorphins released by the brain in anticipation of pain relief from the placebo. Adverse effects following placebo administration may somehow be linked to negative expectations or anxiety, although the mechanism remains uncertain. The efficacy of a placebo may be related to the timing of administration in relation to pharmacologically active medications. It may be tempting to exploit the placebo effect by administering inactive substances to a patient as an alternative to pharmacologic treatment. This practice is demeäning to patients and may lead to discipline or criminal prosecution if 741 the act involves the diversion of controlled substances. Placebo use by paramedics violates ethical principles, deceives patients, and undermines the credibility of the EMS profession. Types of Medication Responses Every medication capable of a therapeutic benefit also can potentially have adverse or toxic effects at excessive doses. Even at appropriate doses, many medications produce harmful or undesired effects in susceptible people. You may prevent or minimize adverse effects by properly selecting the correct medication, route, dose, method of administration, and supportive treatment necessary for each patient. SAFETY Many types of errors can occur in health care. Perhaps most notable are medication and prescription errors, but other, less common errors include wrong patient identification, transfusion errors, preventable suicides, falls, burns, wrong-side procedures, and errors in the transition of care or handoffs. Types of medical errors are listed in Table 13-5.SAFETY Many types of errors can occur in health care. Perhaps most notable are medication and prescription errors, but other, less common errors include wrong patient identification, transfusion errors, preventable suicides, falls, burns, wrong-side procedures, and errors in the transition of care or handoffs. Types of medical errors are listed in Table 13-5. Error Category Specific Errors Diagnostic Error or delay in diagnosis Failure to employ indicated tests Use of outmoded tests or therapy Failure to act on results of monitoring or testing Treatment Error in the performance of an operation, procedure, or test Error in administering the treatment Error in the dose or method of using a drug Avoidable delay in treatment or in responding to an abnormal test inappropriate care Preventive Failure to provide prophylactic treatment Inadequate monitoring or follow-up of treatment Other Failure of communication Equipment failure Other system failure TABLE 13-5 Types of Medical Errors Data from: Kohn LT, Corrigan JM, Donaldson MS, eds. To Err Is Human: Building a Safer Health System. Washington, DC: National Academy Press; 2000. 27 Therapeutic (Desired) Response Pharmacologic interventions are based on a patient's actual or anticipated illness, injury, presenting complaint, sign, or symptom. This condition should match the use or indication listed on the profile for the specific medication. EMS agencies and organizations often formulate protocols that specify which medications should or can be administered in certain situations. Medical directors may authorize off-label uses (discussed earlier) for approved medications when this use reflects accepted medical practice. When the existing protocols or guidelines do not seem appropriate for a patient's needs, in many EMS systems, you may be able to contact online medical control for advice or authorization for medication administration. Medication is administered in a dose intended to produce a desired clinical response for the patient. Sometimes this response may be a complete resolution of the problem following a single dose of medication. In other cases, you may need to administer multiple doses of the same medication to obtain the desired response. Certain medications require frequent repeated dosing, careful titration, or continuous administration to obtain or maintain the desired response. These medications are capable of demonstrating cumulative action, meaning that several smaller doses of medication produce the same desired clinical effect as a single, larger dose of that same medication. This approach can lead to the same therapeutic benefit while decreasing any risks associated with administering too much of a medication by a single, larger dose. Not every medication or situation allows for cumulative action. For instance, many medications require a minimum threshold concentration to cause a clinical effect. Metabolism and eliminationAdverse Medication Effects Adverse and toxic effects are important considerations during medication selection and administration. Pharmaceutical researchers and manufacturers attempt to develop medications that target only specific receptor sites on particular types of cells. Unfortunately, the vast number of possible receptor sites within the body makes medications selective (rather than specific) at best. Even medications that bind with a limited group of receptor sites can cause undesired responses in a variety of cells. The term side effect is often used to mean adverse effect. Although both terms are typically used to mean harmful or potentiälly harmful effects, the term adverse effect more clearly indicates the possibility of serious consequences. Some side effects can be beneficial; for example, a physician may prescribe a specific antidepressant to treat postmenopausal symptoms, such as "hot flashes," because a positive side effect of the drug was identified. Also, a side effect of a medication can be desirable in certain situations and harmful in others. For example, benzodiazepines are used to treat seizure activity and are known to cause sedation. Sedation may be desirable for a combative patient with a head injury but could also jeopardize the life of the same patient if they are vomiting. Various sources may also refer to adverse effects as untoward effects. Both adverse and untoward effects are clinical changes caused by a medication that is not desired and causes some degree of harm" or discomfort to the patient. SAFETY The process of a patient receiving a medication is complex and fraught with opportunities for error, including prescribing, dispensing, administering, and monitoring errors. The uncontrolled prehospital environment creates additional challenges for paramedics when administering medications. Undesired or harmful responses to medication may be directly related to the intended cellular response or to the random activation of unrelated cells throughout the body. Examples of undesired or harmful responses include hypoglycemia after the administration of insulin (exaggerated "therapeutic" effect); profound bradycardia after taking metoprolol, a beta-adrenergic antagonist medication (exaggerated therapeutic effect); and an allergic reaction to a medication (not a therapeutic effect). Examples of common adverse effects include nausea, vomiting, sedation, palpitations, hypotension, hypertension, bradycardia, tachycardia, respiratory depression, and dizziness. Medication reference sources often categorize adverse effects by body system, frequency of occurrence, or severity. YOU are the Paramedic Part 2 On arrival, you are directed to the patient's room. The nursing staff report that the patient is usually awake, alert, and oriented; however, she was noted to be "not herself" over the past several hours and now looks much worse. The staff also reported that the patient was admitted to the skilled nursing facility for complications of diabetes mellitus and was slowly improving until she developed nausea, vomiting, and diarrhea over the past 36 to 48 hours. The patient's temperature was 99.7°F (37.6°C) just before your arrival. Recording Time: 0 Minutes Appearance Level of consciousness Pale skin (Staff confirms her skin tone is pale as compared to its baseline color.) Decreased responsiveness, moaning and incoherent speech, eyes open to deep tactile stimuli Patent AirwayWhen selecting medications consider possible adverse effects about the patient's condition. For example, the respiratory depressant properties of opioid analgesics, such as morphine sulfate, are unlikely to adversely affect a patient with burns who is intubated and being mechanically ventilated; however, an immediate threat to life might result if morphine is given to a patient who is becoming fatigued during an asthma attack. Another example of how adverse effects play a role in decision-making involves choosing between two or more medications that can be given for the same condition. For example, both ondansetron (Zofran) and promethazine (Phenergan) are antiemetic medications. Promethazine causes significant hemodynamic and electrocardiographic (ECG) changes, which are not known to occur with ondansetron. Ondansetron may prove to be a safer antiemetic medication for patients who are particularly susceptible to the adverse effects associated with promethazine. In general, a medication should be avoided or used with caution in patients who are particularly susceptible to the adverse effects associated with that medication. Patients with certain chronic medical conditions are generally more susceptible to the adverse effects of medications than are patients without such conditions. Significant cardiovascular disease, diabetes, impaired immune function, and renal failure are more often associated with greater severity or frequency of adverse effects. Many adverse effects of medications directly relate to these conditions; for example, renal failure hinders the capability of the kidneys to eliminate medications properly. In addition, patients with respiratory distress, shock, multiple trauma, or other life-threatening conditions may be unable to tolerate even mild adverse effects. You must use caution when selecting medications for patients with these conditions. You also need to be alert for adverse effects once medications have been given. Adverse effects may range in severity from changes that are barely perceptible to patients and paramedics to an immediately life-threatening condition requiring aggressive intervention. For example, certain antidepressant medications can cause cardiomyopathy, a disease of the heart muscle. Some antibiotics and antiseizure medications are known to cause Stevens-Johnson syndrome, a severe, possibly fatal medication reaction that mimics a burn. Several medications cause anemia (löw RBC coünt) through bone marrow suppression or direct hemolysis. Adverse effects occasionally occur that are completely unexpected and not previously known to be associated with a particular medication. These idiosyncratic medication reactions involve abnormal susceptibility to a medication, possibly because of genetic traits or dysfunction of a metabolic enzyme peculiar to an individual patient. Therapeutic Index Pharmaceutical companies and scientists devote intensive efforts to evaluating the safety and effectiveness of a potential medication before it is made available to the public. Animal testing establishes the median lethal dose (LD), which is the weight-based dose of a medication that causes death in 50% of the animals tested. In addition, manufacturers determine the median toxic dose (TDs) for a particular adverse effect of the medication, which means that 50% of the animals tested häd toxic effects at or above this weight-based dose. Human or animal testing also reveals the median effective dose (EDso) for a particular use or indication of the medication. The relationship between the median effective dose and the median lethal dose or median toxic dose is known as the therapeutic index or therapeutic ratio. If there is a significant difference between the median effective dose and the median toxic dose or median lethal dose, the medication is considered safe or possibly even nontoxic. If the ratio is relatively small, however, care patient selection, medication use, and medication monitoring are essential. A relatively unsafe medication may be used in clinical practice if it is the only choice for an otherwise fatal medical condition. Immune-Mediated Medication Response Medications and substances present in the environment can trigger an exaggerated response from the body's immune system, which is described generally as an allergic reaction. Allergic reactions can range from mild skin changes to mültisystem, life-threatening reactions. You may encounter patients with this condition who request EMS assistance or 744 may observe it immediately after administering a medication to a patient for an unrelated condition. Patients who are genetically predisposed to anällergic reaction must typically have an initial exposure and sensitization to a particular allergen. Following the initial exposure, various components of the body's immune system evolve into antibodies that specifically target this type of allergen. If the patient then has a subsequent exposure to this type of allergen, a potentially massive cascade of immune system activity, known as anaphylaxis, begins. In severe cases, this reaction dramatically alters the function of the skin, GI, respiratory, and cardiovascular systems, ultimately manifesting as shock and respiratory failure. Chapter 26, Immunologic Emergencies, includes an additional discussion of the pathophysiology and management of an immune-mediated medication response. Patients predisposed to an allergic reaction, anaphylaxis, or other immune-mediated medication response may report previous reactions to medications, latex, foods, or other substances in the environment. Aspirin and antibiotics most commonly penicillin and sulfa-based antibiotics, are the primary culprits in immune-mediated medication responses. A very small amount of any medication can cause this reaction. An immune-mediated reaction can occur days or weeks after initiating a medication. Patients may also have a medication sensitivity that is not related to an exaggerated immune system response. A mild to severe reaction may occur after the first exposure to a medication or other substance, often presenting with many of the same signs and symptoms as an immune-mediated reaction. The treatment for medication sensitivity is similar to the treatment for an immune-mediated response. Avoid administering medications to patients who have had a serious reaction to the specific medication (or medication in the same class) unless the adverse effect is clearly dose-related and can be lessened by judicious administration and careful monitoring. 贝州）米 Words of Wisdom Do not be afraid to ask the same patient about allergies more than once if multiple medications are being administered. Medication Tolerance Certain medications are known to have decreased efficacy or potency when taken repeatedly by a patient, a state known as tolerance. One theory suggests that tolerance results from a mechanism that reduces the number of cell receptors available for binding with a particular medication, a process known as down-regulation. The body compensates for the effects of a medication by increasing the metabolism and/or elimination" of the medication, resulting in a decreased concentration of the medication present near receptor sites. In some instances, the desirable effects continue while other unintended or adverse effects decrease. In other situations, adverse effects persist or increase while additional medication is required to achieve the same therapeutic goal. Repeated exposure to a medication within a particular class, such as opioids or benzodiazepines, can cause a tolerance to other medications in the same class. This phenomenon, known as cross-tolerance, becomes problematic when patients use or abuse medications, drugs, or chemicals regularly and then require medications from that class for a legitimate medical purpose. Determining the appropriate dose for these patients can prove quite challenging, and often results in them receiving inadequate or excessive doses of therapeutic medications. A similar condition, known as tachyphylaxis, occurs with certain medications. Giving repeated doses of medication within a short time frame can rapidly cause tolerance, making the medication virtually ineffective. Tachyphylaxis is likely to occur with certain sympathomimetic medications (discussed läter) and may occur with other medications that you may administer, such as nitroglycerin and dobutamine. Words of Wisdom Consider patient tolerance, IV infiltration or disconnect, or possible medication tampering whenever the administration of a controlled substance does not produce the expected clinical effect. Medication Abuse and Dependence Certain classes of medications and similar groups of illicit chemicals have serious potential for misuse and abuse. Some people may choose to experience many of the desired clinical effects from medications or chemicals even when they do not have an underlying medical condition or symptom. Patients who receive certain medications for legitimate medical conditions may continue to use these medications long after their initial medical condition has resolved. It is often difficult to determine whether an appropriate medical indication for certain medications continues to exist. In the course of your EMS practice, you are almost certain to encounter patients who misuse or abuse medications, illicit drugs, and other chemicals. Two distinct groups of medications and chemicals are especially susceptible to misuse and abuse: stimulants and depressants. Stimulant chemicals cause a transient increase in physical, mental, or emotional performance. Caffeine, and amphetamines are stimulants that have serious potential for misuse or abuse. In general, these medications increase a person's level of consciousness, increase the heart rate, increase blood pressure (BP), and otherwise activate the sympathetic nervous system. The immediate or long-term effects of stimulant medications have the potential to become life-threatening. Depressant medications and chemicals, in contrast to stimulants, reduce CNS and sympathetic nervous system functioning, causing sedation, anxiolysis, respiratory depression, bradycardia, hypotension, and a variety of similar clinical symptoms. Benzodiazepines, alcohol, and opioids are common depressant substances. Toxicity from depressänt substances is also potentially life-threatening following acute or long-term exposure. Repeated exposure to certain medications or chemicals causes a patient to experience habituation, an abnormal tolerance to the adverse or therapeutic effects associated with a substance. In essence, the body adapts to accommodate the exposure and protect itself from the severity of clinical changes associated with a substance. Prolonged or significant exposure to depressants, stimulants, and other medications and chemicals can cause some degree of dependence. Dependence is the physical, emotional, or behavioral need for these substances to maintain a level of "normal" function. When it exists, the person has adapted to the frequent presence of the substance. In the absence of the substance, adverse clinical effects occur. In severe cases, abrupt withdrawal from a substance can precipitate life-threatening clinical changes. Medication Interactions Patients receiving multiple medications, drugs, or other chemicals are at risk of an unintended interaction between the various substances, possibly leading to unexpected results. Undesirable medication interactions are referred to as medication interference. You should consider the possibility of illicit drugs, over-the-counter and prescribed medications, and herbal remedies interacting with any medications that might be given to patients. As patents are prescribed greater number of medications to treat chronic medical conditions, the risk of a medication interaction increases dramatically The most obvious concern with medication interactions is incompatibility during administration. When given simultaneously through the same IV tubing, the chemical composition of some medications will change, possibly creating solid particles in the tubing, which then travel into the patient. Other medication combinations will deactivate one or more of the medications, making them ineffective. Medications also require the use of the proper IV solution, as some can be mixed only in normal saline or dextrose-containing solutions. Consult a reliable medication reference source before administering multiple medications, especially continuous medication infusions, through the same IV tubing. Notably, sodium bicarbonate and furosemide are two medications used in the prehospital setting that are incompatible with several other common prehospital medications. A medication can increase the effect, decrease the effect, or alter the effect of another medication within the body. Table 13-6 describes various types of medication interactions. Interaction Addition or summation to medications with a similar effect combine to produce an effect equal to the sum of the individual effect of each medication (eg, 1 + 1 = 2). The antipyretic properties of acetaminophen (Tylenol) and the antipyretic properties of ibuprofen (Motrin, Advil) combine to reduce a fever in patients with fevers that could not be controlled by either medication alone. SynergismTwo medications with a similar effect combine to produce an effect greater than the sum of the medications' effects. Patients experience profound sedation when IV opioid medications such as fentanyl (Sublimaze) are given with IV benzodiazepines such as midazolam (Versed), are greater than the expected sum of these two medications. PotentiationThe effect of one medication is greatly enhanced by Promethazine (Phenergan) is given to increase the the presence of another medication, which does the effects of codeine or other antitussives (cough does not produce the same effect.suppressants) for more improved relief of cough than is achieved with the antitussive alone. Altered absorptionThe action of one medication increases or decreases the ability of another medication to be absorbed by the body. For example, medications that increase or decrease gastrointestinal pH or motility may increase or decrease the absorption of other medications taken orally. Famotidine (Pepcid), an H, blocker, can reduce the absorption of ketoconazole (an antifungal) or certain cephalosporin antibiotics. Altered metabolism The action of one medication increases or decreases the metabolism of another medication within the body. For example, many medications (and certain foods) alter the performance of the Fluconazole (Diflucan), an antifungal medication, inhibits the function of cytochrome P-450 enzyme CYP3A4, significantly increasing bleeding risks associated with warfarin (Coumadin), an anticoagulant medication. Cytochrome P-450 system in the liver, which is responsible for the metabolism of a variety of other medications. Altered distributions presence of one medication alters the area The anticonvulsant medication valproic acid (Depakote, available for the distribution of another medication Depakene) competes with another anticonvulsant in the body, which becomes important when both medications, phenytoin (Dilantin), cause potential medications to be bound to the same site, such as increased or decreased serum levels and possibly Altered eliminationMedications may increase or decrease the Ethanol decreases the metabolism of warfarin functioning of the kidneys or other route of (Coumadin), which may predispose the patient to elimination, influencing the amount of or duration of bleeding risk of the effect of another medication on the body Physiologic (drug)Two medications, each producing opposite effects, are present simultaneously, resulting in minimal or no clinical changes. Sodium nitroprusside (Nipride) and dobutamine (Dobutrex) are often given simultaneously for cardiogenic shock. By itself, dobutamine increases cardiac output, possibly causing an elevated BP. Sodium Principles of Pharmacokinetics You must carefully consider the pharmacokinetic properties of any medication you are considering administering to a patient. As a medication is administered, the body begins a complex process of moving that medication, possibly altering the medication's structure, and ultimately removing the medication from the body. The medication dose, route of administration, and patient's clinical status will largely determine the duration and effectiveness of the medication (see the section Principles of Pharmacodynamics, earlier in this chapter). Actions of absorption, distribution, metabolism, and elimination are discussed in detail in the following text. The pharmacokinetics section of a medication profile typically states the onset, peak, and duration of the effect of the medication. These values vary by route of administration and may have a broad range, depending on the characteristics of individual patients. The onset and peak of a medication are generally related to absorption and distribution. In particular, a minimum dose or concentration of medication must be present at certain sites in the body for clinical effects to occur (see the earlier section Principles of Pharmacodynamics). The duration of effect is generally related to medication metabolism and elimination. As the amount of a medication found near cell receptors (or another site of action) decreases, the clinical effects caused by the medication begin to decrease, and normal function resumes. If a medication permanently binds with a receptor site or irreversibly alters the function of a cell, the duration of its effect is determined by the body's ability to regenerate cells. In these cases, the duration of effect may be almost entirely unrelated to the dose or concentration of medication present in the body. A single dose of aspirin, for example, is rapidly eliminated by the body, usually within several hours, but can cause an inhibition of platelet activity lasting for 3 to 10 days. Street Smarts Communicating the time of onset and peak of medication to the patient can build trust and credibility. Routes of Medication Administration Medication must enter the body to provide a clinical benefit. Thus, you need to select a route of administration capable of delivering an appropriate amount of medication to the correct location within the patient's body. The route of administration is determined by the physical and chemical properties of the medication, the routes of administration available for a specific patient, and how quickly the effects of the medication are needed. The chosen route of administration determines the percentage of the unchanged medication that reaches the systemic circulation. This percentage, known as bioavailability, varies significantly from one medication to another, except when administered by the IV route. Medications administered by the IV route, by definition, have 100% 748 bioavailability. Bioavailability is irrelevant for medications that are sequestered in the Gl tract, such as activated charcoal and certain cathartic medications. In contrast, it is a critical consideration for other medications that are poorly absorbed by certain routes or subject to immediate metabolism by the liver before reaching systemic circulation. Several important groups of medications, such as beta blöckers and calcium channel blockers, have a relatively low bioavailability when taken orally. The IV doses of these medications are often lower than the oral doses when given for the same indication. Lidocaine and fentanyl are generally not given orally because of their low bioavailability with this route. Various routes of administration available to paramedics are discussed in the following sections. Many medications are prescribed for chronic medical conditions and several important prehospital medications are administered into the Gl system. Use of this route requires that a patient be responsive and able to swallow or have a nasogastric tube or an orogastric tube in place. Aspirin, antipyretic medications, activated charcoal, diphediphenhydramine oral giucoglucoseprehospital medications that may be administered into the Gl system. Once administered via this route, medication absorption varies depending on several factors Table Factors Affecting Gl Medication Absorption Factor Gl motility GI PH The presence of food, liquids, or chemicals in the stomach Abbreviation: Gl, gastrointestinal Effects on Medication Absorption The ability of medication to pass through the Gl tract into the bloodstream Perfusion of the Gl system (may be decreased during systemic trauma or shock) Injury or bleeding in the Gl system (both can alter Gl motility, decreasing the time that oral medications can be absorbed) In addition to these factors, Gl medications may be subject to first-pass metabolism. The medication passes from the Gl tract into the portal vein, which brings it directly into the liver. Once in the liver, metabölism occurs, altering and potentially inactivating the medication before it ever reaches systemic circulation. This first-pass metabolism can be exploited if it changes a previously inactive medication into an active medication. Codeine, for example, undergoes a significant first-pass effect in which a portion of the medication can be converted to morphine, a more potent analgesic, by the liver. Metäbolism of medication may also occur within the GI tract and as the medication enters the bloodstream. The bioavailability of medications given orally or through a nasogastric or an orogastric tübe can range from 5% to 100%, depending on the particular medication and the effect of first-pass metabolism. Several cardiac medications, such as metoprolol and verapamil, are subject to significant first-pass metabolism when taken orally. The reduction in bioavailability due to first-pass hepatic metabolism has already been taken into account with oral dosing, explaining why the oral döses are significantly higher than the IV doses of these medications when given for the same purpose. Patients with hepatic (liver) dysfunction are at risk of toxicity when these medications are given orally, even at conventional doses, because the first-pass effect is impaired in these individuals, such that a greater quantity of the medication reaches their systemic circulation. Endotracheal Administration ACL protocols emphasize using the IV or 10 routes of medication administration over the endotracheal route. If the endotracheal route is chosen, sources recommend administering at least 2 to 2.5 times the IV dose for medications approved for this route, followed by a 5- to 10-mL flush with sterile water or normal saline.? With improved 10 techniques and devices, it is likely that the use of the endotracheal route of medication administration will become increasingly limited. However, you may still administer bronchodilators or mucolytic medications in specific critical care settings via the endotracheal route. Intranasal Administration With the intranasal route of medication administration, liquid medications are converted into a fine mist that is 749 sprayed into one or both nostrils. Fentanyl, midazolam, and naloxone can be administered using this route, with their resulting effectiveness often being equal to or better than that of the same drugs given by other methods. Medication absorption occurs rapidly through this route, and the bioavailability of intranasal medications appears close to 100% in certain studies. Other studies suggest that this method is superior to the IV and rectal routes of administration. Nasal medication administration can occur almost immediately, without delay för initiating an IV line, especially when IV access is difficult or impossible to obtain. Additionally, nasal administration does not place you at risk for a needlestick injury when treating uncooperative patients. Intravenous Administration The IV route remains the preferred method for administering most medications used in the prehospital setting. A small-diameter catheter is inserted into a peripheral or external jugular vein, allowing medications to be administered directly into the systemic circulation. In special situations, you may be permitted to use permanent indwelling venous catheters or large-bore catheters that have already been inserted into central veins by other health care professionals. The bioavailability of IV medication is 100% by definition. Medications administered by the IV route have an onset of action Significantly quicker than the onset of action for medications given orally or through an orogastric or nasogastric tube, often allowing an immediate response or creating the ability to titrate a medication carefully in a rapidly evolving clinical situation. Several important limitations apply regarding the IV route of medication administration. First, access can be challenging in some groups of patients- specifically, patients who have abused iV drugs, patients in profound shock or with cardiovascular collapse, patients with morbid obesity, and patients with certain chronic medical conditions such as diabetes and renal failure. Second, the IV access procedure can cause pain or infection and is somewhat time-consuming. Finally, uncontrolled scenes, environmental extremes, and movement of the transport vehicle make IV access challenging in the prehospital setting. Establishing IV access is discussed further in Chapter 14, Medication Administration. Words of Wisdom Frequently reassess the IV site for infiltration or tubing disconnect during transport. Confirm that the IV is still working properly during patient turnover, especially if the medication being administered has a high potential to cause an adverse effect. The infiltration of IV medication into tissues around the blood vessel is a significant concern for paramedics. Certain medication classes, such as sympathomimetics and electrolyte solutions, can cause significant pain and tissue damage when they accumulate in surrounding tissues. In extreme cases, tissue death will occur in affected areas, leaving a large area of necrotic tissue or skin. Intraosseous Administration The l0 route of medication administration provides a viable alternative when IV access cannot be obtained. When this route is used, a needle is inserted through the patient's skin and into the bone. The tip of the needle pierces the hard, outer layer of bone and enters the softer bone marrow. Vascular uptake from the bone marrow provides a reliable route for medications and IV fluids Table 13-8. Chapter 14, Medication Administration, describes the technique for 10 access in greater detail. TABLE 13-8 Veins Used During I0 Infusion Intraosseous Site Proximal tibia Femur Distal tibia (medial malleolus) Vein Popliteal vein Femoral vein Great saphenous vein Axillary vein Any medication or fluid that can be administered by the IV route can also be administered by the 10 route. Infusion rates for lO fluids are comparable to IV rates when a pressure bag or mechanical infusion device is used. The 10 devices can generally be left in place for up to 24 hours, allowing for their ongoing use as a medication or fluid administration route until IV access can be obtained. Administration by the l route is contraindicated in bones that are fractured. It is also discouraged when patients have bone diseases or skin infection over a possible insertion site. Newer devices allow I0 insertion in a variety of anatomic locations and across the spectrum of patient ages and weights. Intramuscular AdministrationSome medications used in the prehospital setting can be administered by the intramuscular (IM) route. With this administration technique, sterile medication is drawn into a syringe attached to a needle and injected into one of the patient's larger muscles. This route is used when IV access cannot be established or when the clinical situation requires immediate medication administration that cannöt wait for IV access. Medications have a bioavailability ranging from 75% to 100% following IM administration. The absorption rate is determined by the accuracy of the injection landmark and the perfusion to the chosen muscle. Suddenly, placing you or other responders at risk for a contaminated needlestick. Auto-injection devices, such as the quantity of medication. Unfortunately, these devices usually do not retract the needle following administration, which means they present the risk of a contaminated needlestick. You should confirm that a medication is appropriate for IM use before administering it via this route. Even if a medication is safe for IM use, medication reference sources may indicate that a particular muscle should be used or recommend a specific injection technique. Many medications are safe for IV use but can cause significant injury if given by the IM route. Other medications are indicated only for IM use and will cause complications if given by the IV. Subcutaneous Administration Subcutaneous medication administration is similar to IM administration. In this technique, a sterile medication solution is drawn into a syringe attached to a needle. The medication is then injected into various subcutaneous tissue sites throughout the body. The anterior part of the äbdömen, just outside the umbilicus, and the skin overlying the triceps muscle are common sites for subcutaneous injection. Compared to IM needles, the needles for subcutaneous administration are shorter and have a smaller diameter. Certain medications may be indicated for subcutaneous use only and should not be given by the IV route, even if a patent IV line is already in place. The slower absorption that occurs through the subcutaneous tissue may prevent adverse cardiovascular effects, as compared with the nearly instantaneous absorption that occurs with IV administration of the medication. Consult advanced life support (ALS) protocols or a reliable medication reference for specific information about the subcutaneous administration of a medication. The techniques for subcutaneous and IM medication administration are discussed in greater detail in Chapter 14, Medication Administration. Dermal and Transdermal Administration You may encounter patients in the prehospital setting who are receiving medication via the transdermal route. Patches commonly containing nicotine, antiemetics, analgesics, nitroglycerin, or other medications may be placed in various locations on the body. Because transdermal medications may alter a patient's clinical presentation or interfere with the medications you will administer during the EMS response, ask a patient or family member if a transdermal medication patch is in place while obtaining a patient's medication history. Transdermal patches deliver a relatively constant dose of medication over an extended period. Changes in patient temperature or perfusion may alter medication delivery to the patient, potentially causing significant clinical changes In addition, transdermal patches often contain a large quantity of medication. If these patches are chewed or ingested, particularly by children, life-threatening toxic effects are possible. Sublingual Administration Nitroglycerin is frequently given to patients using the sublingual (SL) route of administration. Nitroglycerin tablets are placed under a patient's tongue or nitroglycerin is sprayed under the patient's tongue, where it is absorbed rapidly by 751 of the mucous membranes, resulting in a relatively quick onset of action. The bioavailability of SL nitroglycerin is quite low, so relatively large doses are required when this route is used compared with an IV infusion-close to 100 times larger for initial dosing. Patients must be responsive and alert to receive SL medications. In addition, a lack of moisture or saliva in a patient's mouth may significantly delay the absorption of SL medications. In this case, the spray formulation is preferable over SL tablets. You may also encounter patients receiving certain analgesic medications by lozenges and other medications administered sublingually using lollipops, gums, and orally dissolving tablets. Inhaled or Nebulized Administration * Bronchodilator: Metered-Dose Inhaler Some medications may be inhaled or nebulized into the respiratory tract, providing paramedics with a vital route of medication administration. Oxygen is an example of an inhaled prehospital medication. You may also administer or assist patients in administering respiratory medication using a metered-dose inhaler (MDI), typically for asthma or chronic obstructive pulmonary disease (COPD). Activation of the MDI converts the liquid medicine into a gas, allowing the medication to pass into the patient's lungs. When used with a spacer, MDis are at least as effective as nebulizers for administering bronchodilator medications. Medication in liquid form may also be nebulized (converted into a fine spray) for administration directly into the respiratory system. With this administration technique, tubing with oxygen or compressed air is attached to a small chamber, creating a mist as the gas passes through the liquid medication. The chamber is attached to a mouthpiece or a mask, allowing patients to receive droplets of medication with each inspired breath. Unfortunately, a portion of the medication is lost during exhalation and during hanses in patient respiration Nehulized medications are tvnicallSome medications may be inhaled or nebulized into the respiratory tract, providing paramedics with a vital route of medication administration. Oxygen is an example of an inhaled prehospital medication. You may also administer or assist patients in administering respiratory medication using a metered-dose inhaler (MDI), typically for asthma or chronic obstructive pulmonary disease (COPD). Activation of the MbI converts the liquid medicine into a gas, allowing the medication to pass into the patient's lungs. When used with'ä spacer, MDIs are at least as effective as nebulizers for administering bronchodilator medications. Medication in liquid form may also be nebulized (converted into a fine spray) for administration directly into the respiratory system. With this administration technique, tubing with oxygen or compressed air is attached to a small chamber, creating a mist as the gas passes through the liquid medication. The chamber is attached to a mouthpiece or a mask, allowing patients to receive droplets of medication with each inspired breath. Unfortunately, a portion of the medication is lost during exhalation and during any pauses in patient respiration. Nebulized medications are typically administered to treat bronchospasm or airway edema. Albuterol, levalbuterol (Xopenex), and ipratropium bromide (Atrovent) are nebulized medications available in the prehospital setting. In some instances, you may be instructed to administer other medications by nebulizer. Be aware that nebulized medications have the potential to cause bronchospasm. Rectal Administratio