Pharmacology Midterm notes ALL SOLUTION 2024 EDITION GUARANTEED GRADE A+

half life Half-life (t½) is an important pharmacokinetic measurement. The metabolic half-life of a drug in vivo is the time taken for its concentration in plasma to decline to half its original level. Half-life refers to the duration of action of a drug and depends upon how quickly the drug is eliminated from the plasma. The clearance and distribution of a drug from the plasma are therefore important parameters for the determination of its half-life. B max The maximum amount of drug or radioligand, usually expressed as picomoles (pM) per mg protein, which can bind specifically to the receptors in a membrane preparation. Can be used to measure the density of the receptor site in a particular preparation. Silent Antagonist A drug that attenuates the effects of agonists or inverse agonists, producing a functional reduction in signal transduction. Affects only ligand-dependent receptor activation and displays no intrinsic activity itself. Also known as a neutral antagonist Duration of Action The duration of action of a drug is the length of time that particular drug is effective. Duration of action is a function of several parameters including plasma half-life, the time to equilibrate between plasma and target compartments, and the off rate of the drug from its biological target. agonist A drug that binds to and activates a receptor. Can be full, partial or inverse. A full agonist has high efficacy, producing a full response while occupying a relatively low proportion of receptors. A partial agonist has lower efficacy than a full agonist. It produces sub-maximal activation even when occupying the total receptor population, therefore cannot produce the maximal response, irrespective of the concentration applied. An inverse agonist produces an effect opposite to that of an agonist, yet it binds to the same receptor binding-site as an agonist. antagonist A drug that attenuates the effect of an agonist. Can be competitive or non-competitive, each of which can be reversible or irreversible. A competitive antagonist binds to the same site as the agonist but does not activate it, thus blocks the agonist's action. A non-competitive antagonist binds to an allosteric (non-agonist) site on the receptor to prevent activation of the receptor. A reversible antagonist binds non-covalently to the receptor, therefore can be "washed out". An irreversible antagonist binds covalently to the receptor and cannot be displaced by either competing ligands or washing. desensitization A reduction in response to an agonist while it is continuously present at the receptor, or progressive decrease in response upon repeated exposure to an agonist. potency A measure of the concentrations of a drug at which it is effective. Mechanism of Action (MOA) Refers to the specific biochemical interaction through which a drug substance produces its pharmacological effect. efficacy Describes the way that agonists vary in the response they produce when they occupy the same number of receptors. High efficacy agonists produce their maximal response while occupying a relatively low proportion of the total receptor population. Lower efficacy agonists do not activate receptors to the same degree and may not be able to produce the maximal response. therapeutic window The therapeutic window is the amount of a medication between the amount that gives an effect (effective dose) and the amount that gives more adverse effects than desired effects. For instance, medication with a small pharmaceutical window must be administered with care and control, e.g. by frequently measuring blood concentration of the drug, since it easily loses effects or gives adverse effects. Pharmacokinetics Absorption: Absorption is the process whereby a substance entering the body is assimilated by it. For proper pharmacokinetics study, it is necessary to know both the rate and the extent to which the active substance or therapeutic moiety are absorbed. They include substances intended to produce / not produce systematic effects. Distribution: Distribution is the dispersion or dissemination of substances throughout the fluids and tissues of the body. Metabolism:Metabolism is the process whereby a substance is irreversibly transformed into metabolites. Excretion: SweatExcretion is the elimination of the substance from the body. In rare cases, not all substances are eliminated; some drugs irreversibly accumulate in a tissue in the body. factors affecting absorption Rate of dissolution Surface area Blood flow Lipid solubility pH partitioning factors affecting distribution Blood flow to tissues Ability to exit the vascular system Blood-brain barrier Protein-binding capacity Xenobiotics Xenobiotics are substances that are foreign to the body. These substances are usually synthetic chemical compounds; medications are a common xenobiotic. All xenobiotics, including medications, have the potential to adversely affect the body. The extent of adverse effects correlates to the rate of absorption, distribution, metabolism, and excretion of the medication, which determines the degree of chemical exposure in the body. Fortunately, the body has developed mechanisms to prevent the absorption of xenobiotics and to eliminate them as harmless metabolites. On occasion, a xenobiotic may be transformed into a toxic metabolite. Cytochrome P450 (CYP450) are xenobiotic-metabolizing enzymes necessary for the production of cholesterol and steroids and the detoxification of chemicals and drug metabolism. These enzymes are bound to a cell membrane (cyto) and contain a heme pigment (chrome and P) that absorbs light at a wavelength of 450 nm when exposed to carbon monoxide, hence their name CYP450. CYP450 enzymes are thought to be the major family or system of enzymes responsible for phase 1 metabolism in which drugs are oxidized, reduced, or hydrolyzed—the three possible outcomes of phase 1 metabolism. CYP450 system The CYP450 system is comprised of 12 enzymes that are made up of three families (CYP1, CYP2, CYP3) that metabolize drugs and nine families that metabolize endogenous compounds. Many medication interactions are the result of an alteration in CYP450 metabolism. Medications interact with the CYP450 system and may be metabolized by only one CYP450 enzyme (e.g., metoprolol (Lopressor®) by CYP2D6) or by multiple enzymes (i.e., warfarin [Coumadin®] by CYP1A2, CYP2D6, and CYP3A4). Medication responses vary based on enzyme inhibition, enzyme induction, and/ or genetic differences (Larson, 2020). An inducing agent can increase the rate of another drug's metabolism. Therefore, when an inducing agent is prescribed with another medication, the dosage of the other medication may require adjustment given the increased rate of metabolism and the reduced effect of the medication. On the other hand, if a medication is taken with an inhibitor, the level of the drug can increase and result in adverse effects. Substrates are drugs that are metabolized by CYP450. Understanding which drugs are substrates, inhibitors, and inducers will help the NP predict and prevent adverse drug interactions, which is crucial when prescribing antiseizure medications, antidepressants, and antipsychotics. inhibitors Inhibitors are medications that inhibit the metabolic activity of one or more of the CYP450 enzymes. Medications that inhibit an enzyme potentially slows that enzyme's activity or blocks the activity required for the metabolism of other medications, thereby increasing the levels of medications dependent on that particular enzyme for biotransformation. This inhibition prolongs the pharmacological effect, which may result in toxicity. Factors that affect inhibition include the dose and the capacity to bind to the enzyme. Sertraline (Zoloft®) is an excellent example of how the dose inhibits metabolism. At the 50 mg dose, sertraline (Zoloft®) is a mild inhibitor of CYP2D6, whereas it is a potent inhibitor at the 200 mg dose. Some medications, such as erythromycin (E.E.S.®), have a dual action, which means they can both be metabolized by and inhibit the same enzyme. In comparison, medications like terbinafine (Lamisil®) can be metabolized by one enzyme and inhibit another enzyme simultaneously (Larson, 2020). (DECREASE MEDICATION METABOLISM) valproate isoniazid sulfonamides amiodarone chloramphenicol ketoconazole grapefruit juice quinidine Inducers Inducers are xenobiotics (medications and environmental agents) that elevate CYP450 enzyme activity by increasing enzyme synthesis. This action leads to additional sites available for biotransformation. The increased number of sites enhances medication metabolism, decreasing the concentration of the "parent drug" while increasing metabolite production. The half-life of the inducing drug may cause a delay before enzyme activity increases. A decrease in the concentration of a medication metabolized by CYP2C9 (responsible for 10% of drug metabolism) usually occurs within 24 hours after the administration of the medication. Rifampin (Rifadin®) is an example of an inducer with a short half-life. Conversely, medications like phenobarbital are inducers with a very long half-life and may take up to one week after administration before enzyme activity increases. Carbamazepine (Tegretol®) is a potent enzyme inducer and may be metabolized by the same CYP450 enzyme that it induces. Therefore, a medication like carbamazepine (Tegretol®) must be started at low doses and increased at weekly intervals due to the steady decrease in half-life over time (Larson, 2020). Carbamazepine Rifampin Alcohol Phenytoin Griseofulvin Phenobarbital Sulfonylureas (INCREASE MEDICATION METABOLISM) Substrates Substrates are xenobiotics that require the metabolic process of the body to either activate or de-activate the drug. Like inducers and inhibitors, substrates are also medications that require careful prescribing. Frequently, patients may be taking medication (substrate) but require additional medication. Knowing the CYP enzyme and whether it will increase or decrease the substrate (causing it to exit the body faster or have prolonged excretion) is critical to avoid adverse effects. prescribing during pregnancy and breastfeeding Increased GFR= Increased drug excretion . Drug therapy during pregnancy cannot always be avoided, as the health of the embryo or fetus depends on the health of the mother. Chronic asthma is an excellent illustration as uncontrolled maternal asthma is more dangerous to the fetus than the drugs used to treat it. Prescribing medication during pregnancy requires weighing the benefits of the medication against the risks, which is especially challenging when there is little or no evidence of the true risk for the mother and the developing fetus. Clinical trials are limited as pregnant women and newborns are frequently excluded from research due to the vulnerability of these populations, altered pharmacokinetics, and risk of adverse effects. Often research that involves pregnant or breastfeeding mothers and their children is historical, which attempts to reconstruct what happened as a result of drug therapy. Adverse medication reactions during pregnancy are another pharmacological difference. Commonly prescribed drugs may cause serious and long-lasting effects if taken during pregnancy, for the mother and/or the developing embryo or fetus. The gestational age of the fetus is directly relevant. During the 1st trimester, the fetus is at most risk due to the occurrence of rapid growth. During the 3rd trimester, drugs are likely to cross over from the circulation of the mother to that of the child. Teratogenesis or prenatal toxicity is a drug effect of the highest concern that causes structural or functional defects, intrauterine growth retardation, or even fetal death. Teratogens can be difficult to identify due to a lack of controlled trials, the variability in responses to medications, and difficulty in correlating documentation of adverse effects directly back to a specific drug. Examples of drugs with the highest teratogenic potential include medications for neurologic conditions such as antiepileptic drugs, antimicrobials such as tetracyclines and fluoroquinolones, Vitamin A in large doses, some anticoagulants, and hormonal medications such as diethylstilbestrol (DES). Alcohol and cocaine are examples of nonmedical drugs that are known teratogens (Rosenthal & Burcham, 2021). Therefore, the pharmaceutical management of pregnant women requires special consideration to prevent harmful effects for both the mother and the fetus. prescribing to pediatric patients pediatric patients do not process medications in the same way as adults. Dosages are based on weight or body surface area (BSA) and require careful calculation. Unfortunately, dosages are often approximations due to the speed of physiological changes occurring in very young bodies, the inability to dose medications down to singular dosing units (i.e. mg), and the unavailability of pediatric dosing schedules. Moreover, many drugs have age limits stating the drug is 'not appropriate for children under the age of 2 years' (Rosenthal & Burcham, 2021). Due to the physiological changes that occur during childhood that impact the pharmacokinetics of medications, the pediatric population is recognized as a special population for drug therapy. absorption in neonates and infants Oral Administration delayed gastric emptying (adult values reached by 6-8 months)increased absorption for drugs that are absorbed in the stomach decreased absorption for drugs that are absorbed in the intestine slow gastric acidity for 24 hours after birth (adult values reached around 24 months) increased absorption of acid-labile drugs Intramuscular Neonate​​​​​​-slow and erratic due to low blood flow in muscles first few days of life Infancy-increased absorption than in neonates and adults due to increased blood flow Transdermal infants have thin skin with higher rates of blood flow increased absorption increased risk for toxicity from topical drugs prescribing to children Children are also vulnerable to unique adverse effects related to organ immaturity and ongoing growth and development. Examples of age-related effects include growth suppression that can be caused by glucocorticoids, discoloration of developing teeth with tetracyclines, and kernicterus with sulfonamides. Medication adherence is another challenging issue in the pediatric population. Strategies to promote adherence include providing written patient education and requiring return demonstration of medication administration techniques by caregivers. Effective education should include the following: dosage size and timing route and technique of administration duration of treatment drug storage nature and time course of desired responses nature and time course of adverse responses (Rosenthal & Burcham, 2021) prescribing to older adults Predisposing ADR factors in the older adult include: drug accumulation secondary to reduced renal function polypharmacy (the use of five or more medications daily) greater severity of illness presence of comorbidities use of drugs that have a low therapeutic index (e.g., digoxin) increased individual variation secondary to altered pharmacokinetics inadequate supervision of long-term therapy poor patient adherence Although many predisposing ADR factors are beyond the control of the healthcare provider, strategies to reduce ADRs include: obtaining a thorough drug history that includes over-the-counter medications considering pharmacokinetic and pharmacodynamic changes due to age monitoring the patient's clinical response and plasma drug levels using the simplest regimen possible monitoring for drug-drug interactions and iatrogenic illness periodically reviewing the need for continued drug therapy encouraging the patient to dispose of old medications taking steps to promote adherence and to avoid drugs on the Beers list (Rosenthal & Burcham, 2021) Beers criteria The Beers Criteria includes five lists that describe certain medications and situations and include: potentially Inappropriate Medication (PIM) use in older adults potentially Inappropriate Medication (PIM) use in older adults due to medication-disease or medication-syndrome interactions that may exacerbate the disease or syndrome medications to be used cautiously in older adults clinically significant drug interactions that should be avoided in older adults medications to be avoided or dosage decreased in the presence of impaired kidney function in older adults (American Geriatric Society Beers Criteria Update Expert Panel, 2019) Medication adherence in older adults is also an important consideration to optimize outcomes. Strategies to promote adherence include: simplifying drug regimens providing clear and concise verbal and written instructions using an appropriate dosage form clearly labeling and dispensing easy-to-open containers developing daily reminders monitoring frequently affordability of drugs support systems According to Rosenthal & Burcham (2021), nine factors impact the outcome of medication and include: bodyweight and composition age pathophysiology tolerance placebo effect variability in absorption genetics and pharmacogenomics gender and race-related variations comorbidities and drug interactio Which of the following is needed before implementing genetic testing? informed consent Which fears are a common issue in genetic testing? discrimination Which policy was implemented to protect patients from discrimination by employers and insurance providers based on genetic information? Genetic Information Nondiscrimination Act (GINA) full practice scope Nurse practitioners have the autonomy to evaluate patients, diagnose, order and interpret tests, initiate and manage treatments and prescribe medications, including controlled substances without physician oversight. reduced-practice scope Nurse practitioners are limited in at least one element of practice. The state requires a formal collaborative agreement with an outside health discipline for the nurse practitioner to provide patient care. restricted-practice scope Nurse practitioners are limited in at least one element of practice by requiring supervision, delegation, or team management by an outside health discipline for the nurse practitioner to provide patient care. rational drug selection Administering medications and prescribing medications are two distinct processes. Prescription writing requires prudent and deliberate decision-making processes to maintain patient safety and reduce liability, including: documentation of a provider-patient relationship for the recipient of the prescribed medications documentation of a thorough history and physical examination for the recipient documentation of discussions regarding risk factors, side effects, or therapy options documentation of drug monitoring or titration plan, if applicable documentation of consultations, if any avoidance of prescribing medications for self, family, or friends Rational drug selection requires a logical approach that includes the formulation of a diagnosis based on clinical reasoning and the selection and monitoring of the most appropriate pharmacological treatment (Rosenthal & Burcham, 2021). Considerations include: It is of critical importance that providers ask patients if they have difficulty obtaining their medication because it is cost prohibitive. It is the provider's responsibility to keep abreast of new recommendations or changes in guidelines and to incorporate these into their prescribing practices. The drug you want may not be available in your facility or at a specific pharmacy. This can affect your choice in medications. There are very few medications that do not interact with either another medication or a food. Polypharmacy greatly increases the risk for interactions. Some of these interactions are negligible, but some can have life-threatening consequences. All drugs have side effects. Some are adverse, and some may be beneficial. Unfortunately, your patient may have an allergy to that medication or class of drug. It is of critical importance to determine the type of reaction and to document in the patient's chart. Then, selection of an appropriate drug may begin. Many drugs are metabolized and eliminated by the liver and kidneys. If these systems are impaired, this can lead to increased adverse effects and possible medication overdose. Some drugs require frequent monitoring at initiation or throughout the duration of treatment. Populations that deserve special mention when thinking about medications include pregnant or nursing mothers, and older adults. prescription elements E-Script Prescriptions Widely accepted Quick and easy transfer to pharmacy Minimizes errors DEA scheduled drugs can't be ordered electronically Written Prescriptions Must contain all elements May have pre-populated information Write legibly Use ink Avoid error prone abbreviations Never sign blank copies Tamper resistant scripts are often required Telephone Prescriptions Convenient Must contain all elements Schedule II drugs cannot be prescribed or refilled by phone Refill Prescriptions Consider guiding questions found in textbook Consider any monitoring needs between refills complete prescription contact information provider name, license number, DEA Pt Name, DOB, allergies medication name, strength, number to dispense, indication, dose, frequency, refills medication education should include medication name: generic vs. trade name purpose: the reason for taking the medication, including the desired effect dosing regimen: how much medication, how often, and the time of day administration: preparations needed for taking, such as with or without food adverse effects: all possible risks and how to manage them special storage needs if needed such as refrigeration or use of the original container associated laboratory testing, including regular appointments food or drug interactions: what to avoid and what measures to take duration of therapy: length of administration medication monitoring All medications require monitoring to achieve a therapeutic outcome. If the medication is not creating the desired outcome, it likely will not be continued. Every drug has side effects, requiring ongoing assessment of the ratio of benefits and risk. According to Rosenthal and Burcham, (2021) drug monitoring has three aims: determining therapeutic dosage evaluating medication adequacy identifying adverse effects Many drugs are toxic or damaging to specific organs in the body such as the liver, kidney, and heart. Determining whether a specific drug is responsible for an observed adverse event can be difficult due to underlying illnesses and complex medication regimens that include more than one drug. Reducing ADRs is the responsibility of the entire healthcare team. Prescribers should follow Food and Drug Administration (FDA) guidance issued through special alerts and management guidelines. All medications should be checked for black box warnings. Black box warnings are issued when a drug is found to have serious or life-threatening risks. These drugs remain eligible for prescribing, but their risk must be carefully considered in discussion with the patient (Rosenthal & Burcham, 2021). types of acute pain Referred Pain Pain that is present in an area removed or distant from its point of origin. Acute Somatic Pain Arises from connective tissue, muscle, bone and skin. Sharp and localized or dull and non-localized Responds best to: acetaminophen, corticosteroids, NSAIDs, opiates, local anesthetics, ice, massage Acute visceral pain Pain in the internal organs and abdomen Poorly localized (C-fibers) Radiates Most responsive to opiates May also use corticosteroids, NSAIDs acute pain management opioids: moderate to severe pain, adverse drug reactions- sedation, drowsiness, mental clouding, constipation, nausea and decreased appetite, sexual dysfunction, tolerance/dependency (all adr worse when combined with alcohol or benzos) discuss length of treatment and non-opiate therapy, may interact with any other drug that causes a sedative effect, is med effective? if not, reassess cause of pain acetaminophen: mild to moderate pain, mild- 325-650mg every 4-6hrs, children- 10mg/kg every 4-8 hours, moderate pain- 500-1000mg every 4-6 hrs, maximum dose - 4g per 24 hours, children max- 15mg/kg/dose, hepatic injury with OD, renal disease with chronic use, avoid alcohol NSAIDS: use for fever and/or pain, inflammation as an anti-platelet, avoid in pregnancy and renal dysfunction, Adv reactions: GI upset, dyspepsia, abd pain, GI bleed, fluid retention, edema, HTN, renal damage ibuprofen dosing:200-800mg/dose every 6-8 hours, Max: 3200mg/day, children 5-10mg/kg/dose, peds max: 40mg/kg/day. naproxen dosing 500mg then 500mg every 12 hours or 250mg every 6-8 hours, max: 1250mg/day salicylates: use for fever, pain, inflammation, anti-platelet use Avoid in pregnancy, children, and renal dysfunction, dosing for pain 325to 1000mg every 4-6hrs max:4gm/day, arthritis: 3.6 to 5.4gm/day in divided doses adv reactions:GI upset, dyspepsia, abd pain, GI bleed, renal impairment, tinnitus Pt education: dose appropriately, avoid alcohol, watch for signs of toxicity monitor for effectiveness - may need to add opioid agonist Cox2 inhibitors: use for pain and/or inflammation. avoid in pregnancy, children, renal dysfunction, pain after coronary artery bypass graft surgery. use caution in heart failure, htn, fluid retention. dosing considerations for those with renal impairment or cardiovascular disease, adv reactions: GI upset, abd pain, GI bleed, edema, HTN, thrombi events, fluid retention, renal impairment, poor metabolizers of CYP2C9. pt edu: avoid alcohol, avoid ASA and otc meds, may increase risk of MI or stroke. monitor for effectiveness - may need to add opoid antagonist, drug interaction: drugs that inhibit CYP2C9, drugs that are metabolized by CYP2D6, increased risk of renal failure with angiotensin-converting enzyme inhibitors. opioid prescribing An opioid is an agent that works at an opioid receptor, is a derivative from opium, and includes full agonists, partial agonists, mixed agonist-antagonists, and antagonists. Opioids have a variable affinity for certain receptors. Choosing an appropriate opioid analgesic depends on several factors, such as the desired onset and duration of action, and consideration of potential adverse reactions. Doses are not equivalent; absorption and therapeutic effects are impacted by the route and individual characteristics. Short-acting opioids should be used exclusively for the treatment of acute pain in opioid naïve patients (as opposed to opioid-tolerant patients). Titration to optimal therapeutic effects is faster, safer, and easier with immediate-release opioids (as opposed to extended-release opioids). Unintentional overdose may be more likely when opioid therapy begins with long-acting opioids in opioid naïve patients. In 2016, the CDC released the Guideline for Prescribing Opioids for Chronic Pain (Links to an external site.) in response to the epidemic. This guideline addresses three main principles to improve opioid prescribing, including: determining when to initiate or continue opioids for chronic pain opioid selection, dosage, duration, follow-up, and discontinuation assessing risk and addressing harms of opioid use 12 Essential Considerations for Safe Pain Management: Opioids are not first-line therapy Establish goals for pain and function Discuss risk and benefits Use immediate-release opioids when starting Use the lowest effective dose Prescribe short durations for acute pain Evaluate benefits and harms frequently Use strategies to mitigate risk Review PDMP data Use urine drug testing Avoid concurrent opioid and benzodiazepine prescribing Offer treatment for opioid disorder opioid use disorder The alarming increase in opioid prescriptions had led to an epidemic of drug overdose deaths. In 2017, the federal government declared the opioid crisis a national emergency. This epidemic has prompted scrutiny of practices for prescribing opioids for pain management. Use of opioid pain medication has known risks, including overdose and opioid use disorder. The Diagnostic and Statistical Manual of Mental Disorders, 5th Edition, (DSM-IV) describes opioid use disorder as a pattern of use that leads to significant impairment or distress. Typically, this disorder is marked by unsuccessful efforts to reduce or control use resulting in the inability to fulfill work, school, or home responsibilities. Opioid use disorder is different from drug tolerance and physical dependence, which may also exist. Opioid use creates high levels of positive reinforcement, increasing the likelihood of continued use. It is often a chronic lifelong disorder, leading to serious consequences such as disability and death. Although it is similar to other substance use disorders, it has distinct features that have fueled the current opioid epidemic. Opioids can lead to physical dependence in only 4-8 weeks. Abruptly stopping use in chronic users leads to severe symptoms, which motivates continued use to prevent withdrawal. The 2016 CDC guidelines for prescribing opioids recommends calculating the total daily dose of opioids to help identify patients who might benefit from the reduction or tapering of opioids, given the risk of overdose. Opioid use disorder can lead to severe withdrawal symptoms, uncontrolled pain, as well as psychological distress, and suicidal ideation. The U.S. Food and Drug Administration (FDA) has issued a Risk Evaluation and Mitigation Strategy (REMS) drug safety program to reinforce safe medication use. The goals of REMS is to ensure that medication is used according to FDA-approved prescribing and that the benefits outweigh the risk of misuse and abuse. The FDA also requires drug manufacturers to add recommendations about naloxone to prescribing information. Naloxone is used to quickly reverse an opioid overdose. The availability of naloxone must be addressed and an assessment regarding the need for a naloxone prescription must be conducted when prescribing opioids or medications to treat opioid use disorder. Potential addiction must always be carefully considered. In the opioid naïve patient, short-acting opioids are recommended (the lowest effective dose for the shortest period) to reduce the risk of dependence and tolerance. Antagonist precipitated withdrawal can be induced if naloxone (or another antagonist) is given in an individual who is chronically dependent on opioids. preventing opioid OD deaths The number of patients presenting with opioid use disorder is on the rise and early intervention is essential to decrease the risk of death from overdose. The Substance Abuse and Mental Health Service Administration (SAMHSA) (2020) identifies five strategies to prevent overdose deaths: encourage providers, persons at high risk, their family members, and others to learn how to prevent and manage opioid overdose ensure access to treatment for individuals who are misusing opioids or have a substance use disorder ensure ready access to naloxone call 911 for any suspected signs of opioid overdose; administer life-saving services until emergency medical help arrives CONTINUED...