NUR 613: Advanced Pharmacology and Therapeutics PDF

NUR 613: Advanced Pharmacology and Therapeutics: MODULE 01: Virtual Classroom 01 SPRING 2025 Pharmacology: The Basics Drug Any chemical that can a?ect living processes Pharmacology (pharmakon-poison; ology-study of) The study of drugs and their interactions with living systems Clinical Pharmacology The study of drugs in humans Therapeutics (also known as Pharmacotherapeutics) The use of drugs to diagnose, prevent or treat disease or to prevent pregnancy or, the medical use of a drug Pharmacology: The Therapeutic Objective The objective of drug therapy is to provide maximum beneﬁt with minimum harm In order to meet this challenge, there must be: Skill Judgement Knowledge The desire to provide greater good than harm How does this happen? STUDY, LEARN, and APPLY Properties of an Ideal Drug: The Big 3 ENectiveness The most important property a drug can have Safety There is no such thing as a safe drug Selectivity There is no such thing as a selective drug ALL drugs have side eNects The Ideal Drug: The Other Properties Why is all of this important? Reversible Action Predictability Ease of Administration Freedom from Drug Interactions Low Cost Chemical Stability Simple Generic Names WHY IS EACH OF THESE IMPORTANT? Terms Related to Adverse Drug Reactions Allergic reaction Immune response (Type I and Type IV Hypersensitivity Rxns) Determined primarily by the degree of sensitization of the immune system NOT by drug dosage Patient’s sensitivity to a drug can change over time Very few drugs cause severe allergic reactions Penicillins are the most common Allergies may also be induced by sulfonamides ( as well as diuretics, other antibiotics, and oral hypoglycemic agents) Terms Related to Adverse Drug Reactions Idiosyncratic eNect An uncommon drug response resulting from a genetic predisposition Succinylcholine-induced paralysis Usually brief but may last for hours in genetically predisposed patients (acetylcholinesterase deﬁciency) Paradoxical eNect The opposite of the intended drug response For example, when using benzodiazepines for sedation to treat insomnia, excitement may occur instead (especially in children and older adults) Terms Related to Adverse Drug Reactions Physical dependence Develops during long-term use of certain drugs (opioids, alcohol, barbiturates, and amphetamines) A state in which the body has adapted to drug exposure in such a way that an abstinence syndrome will result if drug is discontinued It is important to warn patients against abrupt discontinuation of any medication without ﬁrst consulting a knowledgeable health professional (i.e., the nurse practitioner responsible for the patient’s care) Iatrogenic disease Iatrogenic: Literally, “a disease produced by a healer”; also used to refer to a disease produced by drugs (e.g., drugs for antipsychotic disorders can cause Parkinson’s-like symptoms) Sometimes also called drug-induced disease Essentially identical to naturally occurring pathology ENects of Drugs (Kinetics and Dynamics) Drug-Drug Interaction Addition (potentiation) drugs of similar action-e?ect are additive: 1 + 1 = 2 (Diuretic + 𝛽-blocker) Synergism di?erent drugs enhance the action of another drug: 1 + 1 = > 2 (Bactrim→ two abxs combined) Inhibition the use of one drug antagonizes the e?ect of another drug: 1 + 1 < 2 (Morphine + naloxone) Drug-Drug Interactions (KINETICS) Intensiﬁcation of e?ects Increased therapeutic e?ects Sulbactam and ampicillin Increased adverse e?ects Aspirin and warfarin Reduction of e?ects Inhibitory: Interactions that result in reduced drug e?ects Reduced therapeutic eNects Propranolol and albuterol Reduced adverse eNects Naloxone to treat morphine overdose Factors That Determine the Intensity of Drug Responses (Much more on this later!) How the drug is administered Pharmacokinetics What the BODY DOES TO THE DRUG Pharmacodynamics What the DRUG DOES TO THE BODY Sources of Individual Variation Varies from PERSON TO PERSON Factors that Determine the Intensity of Drug Responses Stages of New Drug Development Phase I: The objective is to evaluate drug metabolism, pharmacokinetics, and biologic eNects. Phase II and III: The objective is to determine therapeutic eNects, dosage range, safety, and eNectiveness. Phase IV: the new drug is released for general use, permitting observation of its eNects in a large population. 18 months of COVID-19 VACCINE NEXT phase of COVID-19 VACCINE Exercise Discretion Regarding New Drugs Be neither the ﬁrst to adopt the new nor the last to abandon the old Balance potential beneﬁts against inherent risks New drugs generally present > risks than older ones Why would you think this? Pharmaceutical reps are in the business of selling drugs Do your due diligence before prescribing a new drug Drugs: “What is in a name? That which we call a rose by any other name would smell as sweet.” (Shakespeare Romeo and Juliet, Act 2, Scene 2) How do we name drugs? Chemical formula 3,3-Dimethyl-7-oxo-6-(2-phenoxyacetamido)-4-thia-1-azabicyclo[3.2.0]heptane-2- carboxylic acid Chemical name Phenoxymethylpenicillin Generic name (o?icial name: Only name used on national board exams) penicillin v Trade name Propicillin® (just one of many trade names) Which Name to Use: Generic or Trade? The little problems with generic names More complicated than trade names The big problems with trade names Single drug can have multiple trade names Adalat CC®, Nifedical XL®, Nifediac CC®, Procardia®, Procardia XL® are all the same drug (nifedipine, a calcium channel blocker) U.S. drugs and drugs outside the United States may have di?erent active ingredients Products with the same generic name may have di?erent active ingredients and di?erent bioavailability For example, Kaopectate® (kayolen) Ways to Classify Drugs Therapeutic Classiﬁcation Pharmacologic Classiﬁcation Drugs grouped by what they treat Grouped by the chemical structure/mechanism of action (MOA) → how they work –Drugs to lower plasma volume –Diuretics –Drugs for high blood pressure (BP) –Calcium channel blockers –Drugs for depression –Selective serotonin reuptake inhibitors (SSRIs) Ways to Classify Drugs Other forms of classiﬁcation are used for speciﬁc purposes. Controlled substances morphine Over-the-counter (OTC) medications Tylenol Homeopathic drugs pollen for treatment of hay fever Herbal remedies rosemary tea SuNixes are helpful (Do Not Learn Yet) Identifying Therapeutic Use Pharmacologic Class Drug Name SuNix Infection Penicillin antibiotic -cillin Amoxicillin Amoxil High cholesterol HMG-CoA reductase inhibitor -statin Simvastatin Zocor Peptic Ulcer Proton pump inhibitor -prazole Omeprazole Prilosec Disease Anticoagulation Low-molecular-weight heparin -parin Enoxaparin Lovenox Diazepam Valium Alprasolam Anxiety Benzodiazepines -epam -olam Xanax Phosphodiesterase type 5 Erectile dysfunction -aﬁl Sildenaﬁl Viagra inhibitor Over-the-Counter Drugs Americans spend about $30 billion annually on over-the-counter (OTC) drugs OTC drugs account for 60% of all doses administered 40% of Americans take at least one OTC drug every 2 days 4x as many illnesses are treated by a consumer using an OTC drug as by a consumer visiting a physician or nurse practitioner The average home medicine cabinet contains 24 OTC preparations Pharmacologic Classiﬁcations: Controlled Substances Abuse Deﬁnitions for Schedule I – V Drugs Potential High potential for abuse Schedule No currently accepted medical use in the United States I* Lack of accepted safety for due of the drug under medical supervision High potential for abuse Schedule Currently accepted medical use in the United States II Abuse may lead to severe psychological or physical dependence Potential for abuse less than schedule I and II drugs Schedule Currently accepted medical use in the United States III Abuse may lead to moderate or low physical dependence or high psychological dependence Lower potential for abuse than schedule III drugs Schedule Currently accepted medical use in the United States IV Abuse may lead to limited physical or psychological dependence relative to schedule III substances Low potential for abuse relative to schedule IV substances Schedule Currently accept4ed medical use in the United States V Abuse may lead to limited physical or psychological dependence relative to schedule IV substances *N indicates that the drug is a non-narcotic. For example, a Schedule III-N drug, such as anabolic steroids has potential for abuse greater than a Schedule IV or Schedule IV-N drug. Sources of Drug Information (information only) Newsletters The Medical Letter on Drugs and Therapeutics: bimonthly Prescriber's Letter: monthly Reference Books Physicians' Desk Reference based upon package inserts Drug Facts and Comparison very comprehensive reference; updated monthly Saunders Nursing Drug Handbook - annual Mosby's Drug Guide for Nurses - annual The Internet If it is on the internet, it must be true, right?! Pharmacokinetics (MOTION) or WHAT THE BODY DOES TO THE DRUG) Factors That Determine the Intensity of Drug Responses: KINETICS (κίνησις→kinetikos – Greek for putting in motion) Pharmacokinetics: Impact of the BODY ON THE DRUG: The FOUR PHASES Absorption → blood GI tract, skin, mucous membranes, direct injection into the blood, muscle Distribution site of absorption to site of action Metabolism liver, kidney, site of action Excretion kidney, bile, stool The 4 Basic Pharmacokinetic Processes (A di?erent visual) Figure 4.1, p. 25., Burchum & Rosenthal All phases of pharmacokinetics depend upon the drug crossing a membrane Channels or pores –smallest of the drugs Transport active—requires energy passive—requires no energy p-glycoprotein: transports a wide variety of drugs OUT of cells Direct—lipid (fat) soluble Di?usion P-Glycoprotein P-glycoprotein: Transmembrane protein that transports a wide variety of drugs out of cells Liver: Transports drugs into the bile for elimination Kidney: Pumps drugs into the urine for excretion Placenta: Transports drugs back into the maternal blood Brain: Pumps drugs into the blood to limit the drug’s access to the brain The 4 Basic Pharmacokinetic Processes (A di?erent visual) Figure 4.1, p. 25., Burchum & Rosenthal Passage of Drugs Across Membranes (Kinetics) For most drugs, movement throughout the body is dependent on the drug’s ability to penetrate membranes directly Most drugs are too large to pass through channels or pores Most drugs lack transport systems that help them cross all the membranes that separate them from their sites of action, metabolism, and excretion Passage of Drugs Across Membranes (Kinetics) A general rule in chemistry states that “like dissolves like” Water dissolves water-soluble materials Fat dissolves lipid-soluble materials Cell membranes are composed primarily of lipids therefore, to directly penetrate membranes, a drug must be lipophilic→lipid soluble (lipo-fat; philic-loving) Absorption (Kinetics) Movement of a drug from its site of administration into the blood The rate of absorption determines how soon e?ects will begin The amount of absorption helps determine how intense the e?ects will be Factors aNecting drug absorption (Think of the pathophysiologic factors that a?ect each of the following) Rate of dissolution Surface area Blood ﬂow Lipid solubility pH partitioning Site of administration How Does the Drug Get There? What Are the Barriers? Absorption Is the medication given correctly? Is the patient adherent to the drug regimen? How is the medication given? orally (PO) rectally (PR) intravenous (IV) subcutaneous (SQ) intramuscular (IM) lungs transdermal transvaginal sublingual (SL) buccal (BUCC) nasal ophthalmic Movement of Drugs Following GI Absorption (Kinetics) Distribution (Kinetics) Movement of drugs throughout the body Blood ﬂow to tissues Exiting the vascular system Entering cells Drug distribution is determined by these three factors: How Does the Drug Get Where It Is Supposed To? (Kinetics) DISTRIBUTION—Transport of the drug from the site of absorption to the site of action (absorption may be direct or indirect) Factors A?ecting Distribution Organ blood ﬂow brain, heart, liver, kidney, placenta: highly perfused-rapid onset of action Plasma Protein Binding almost all drugs are reversibly bound to plasma proteins→ WHY IS THIS IMPORTANT albumin Molecule Size Lipid Solubility Blood Flow to Tissues (Kinetics) Drugs→ blood→ tissues and organs of the body Blood ﬂow determines the rate of delivery Abscesses and tumors Low regional blood ﬂow a?ects therapy Pus-ﬁlled pockets rather than internal blood vessels Solid tumors have a limited blood supply Distribution: Special Circumstances (Kinetics) DISTRIBUTION— Blood-Brain Barrier unique anatomy of capillaries in the central nervous system (CNS)—tight junctions vascular junctions are so tight that they prevent drug passage drugs MUST BE lipid soluble AND have a transport system that allows passage through the cells of the capillary wall the good: prevents passage of toxins the bad: prevents the delivery of helpful therapies for CNS disorders (e.g., antibiotics, chemotherapy) poorly developed in the newborn→ babies are particularly sensitive to drugs that act on the brain Capillaries: The Blood-Brain Barrier Typical capillary Blood-brain barrier Large gaps allow drug passage Tight junction prevents drug passage Distribution: Special Circumstances (Kinetics) DISTRIBUTION— The Placenta separates maternal circulation from fetal circulation NOT an absolute barrier to drugs and other toxins lipid soluble, non-ionized substances freely cross Possible consequences for the fetus »mental retardation »drug dependence »fetal malformations ion trapping-the fetal compartment is more acidic than the mother; non-ionized substances that cross can become ionized in lower pH environments and then get “trapped” in the fetal compartment How Does the Drug Get Where It Is Supposed To? Special Circumstances (Kinetics) DISTRIBUTION— Protein binding: albumin is a HUGE molecule; because of the size, albumin always (well, almost always) remains in the blood (Where have you seen this information before?) Drug molecules reversibly* bind with albumin for TRANSPORT bound drugs-INACTIVE unbound drugs-ACTIVE or FREE dynamic state between inactive and active form of drug-molecules are always leaving and attaching to the transport molecule % of binding is unique to each drug disorders that decrease or increase albumin production will change the free and bound concentrations of drugs (What are some of these disorders?) *This would make sense because a drug molecule that is irreversibly bound to a carrier molecule would serve no purpose. Free at last..... Drug Therapy During Pregnancy: Ion Trapping Protein Binding A. Albumin is the most prevalent protein in plasma and the most important of the proteins to which drugs bind. B. Only unbound (free) drug molecules can leave the vascular system. Bound molecules are too large to ﬁt through the pores in the capillary wall. FIG. 4.10 Movement of drugs after gastrointestinal (GI) absorption. What Does the Body Do to Make the Drug Work? (Kinetics) METABOLISM or BIOTRANSFORMATION –drug is converted to a less active or more active form –ﬁrst pass eNect drugs absorbed from the intestine are transported to the liver where the drug is metabolized to decrease or increase the amount of active drug –metabolites active inactive The Liver (Kinetics)(Kinetics Metabolism: Special Considerations (Kinetics) Induction of drug-metabolizing enzymes –certain drugs may induce liver enzymes that speed the metabolism of the inducing drug as well as other drugs Cytochrome P450 Malnutrition –metabolism may be compromised Infants –Limited drug metabolism due to immature liver because liver enzymes not fully active –Liver is fully mature at one year –Smaller dosages required –May be a?ected by milk Metabolic competition –if two drugs are metabolized by the same system, one will compete with the other; drug levels may not be predictable (remember this from NUR 612 Module 05 [the Kidney] and Module 06 (the Liver]) Special Considerations: The Elderly (Kinetics) THE ELDERLY Absorption Metabolism Decreased gastric acidity Decreased liver function Slowed gastric emptying –Active drug levels may be too low or too high Slower movement through the GI tract –Delayed absorption Excretion Reduced blood ﬂow to the GI tract Decreased kidney function –Decreased ﬁrst pass Competition of multiple drugs for tubular excretion Distribution Decreased cardiac output Vascular disease Competition of other drugs for receptor sites What are comorbid conditions that the elderly experience that would cause these issues? REMEMBER (Kinetics) DRUG Possible increased toxicity secondary to inhibition of the Cytochrome P450 system Special Considerations in Drug Metabolism (Kinetics) Age Induction of drug-metabolizing enzymes First-pass e?ect Nutritional status Competition among drugs What Does the Body Do to Get Rid of the Drug? (Kinetics) EXCRETION: the removal of drugs from the body Renal (kidney): majority of drug excretion healthy vs unhealthy kidneys older vs younger kidneys pH dependence Other bile (liver), sweat, saliva, breast milk, lungs Renal Routes of Drug Excretion Steps in renal drug excretion Glomerular ﬁltration Passive tubular reabsorption Active tubular secretion Factors that modify renal drug excretion pH-dependent ionization Competition for active tubular transport Age (why?) Time Course of Drug Responses (Kinetics) Plasma Drug Levels: Clinical Signiﬁcance drug level of e?ectiveness Minimum E?ective Concentration (MEC) the plasma drug level below which therapeutic e?ects will not occur Toxic Concentration (TC) the plasma drug level above which harm occurs Therapeutic range- The objective of drug dosing is to maintain plasma drug levels within the therapeutic range the AREA BETWEEN MEC and TC (SEE NEXT SLIDE) Time Course of Drug Responses (Kinetics) Single-dose Time Course Latent phase: time from administration to minimal e?ective concentration (MEC) Duration of action: time from MEC to MEC FIG. 4.13 Single-dose time course, p. 41, Burchum & Rosenthal Time Course of Drug Responses (Kinetics) Drug Half-life (t1/2) the time required for the amount of drug in the body to decrease by 50% T1⁄2 is independent of the amount of drug given Drug half-life (t1/2) gives many students a challenge. Do what it takes to understand this. (The videos are helpful.) Time Course of Drug Responses (Kinetics) When the amount of drug eliminated between doses equals the dose administered, average drug levels will remain constant, and plateau has been reached. Plateau is reached in approximately four half-lives. When drug is discontinued, 94% reduction in plasma level occurs in four half-lives and ~97% is removed in ﬁve half-lives. Make sure you understand the concept of plateau and half-life!!! (I cannot be any more direct than this.) First Fourth Discontinuation half-life half-life of drug Time Course of Drug Responses (Kinetics) After repeated doses, –highest level→ peak –lowest level→ trough Fluctuation reduction –continuous infusion –administer depot prep –reduce dose size and decrease time of dose frequency Why is the concept of peak and trough important? (Think about your clinical experience.) Initial At At peak 2 plateau, plateau, MEMORY TRICK→ gms peak is 2x trough ~ = initial peak initial peak Time Course of Drug Responses (Kinetics): The Numbers 4g gms 2 gms Question Drug X with T(1/2) of 12 hrs is given q 12 hrs. If the initial drug peak is 500 mcg/L, what is the drug level just before dose 31 is given? 250 mcg/L 500 mcg/L 1000 mcg/L 2000 mcg/L Question Drug X with T(1/2) of 12 hrs is given q 12 hrs. If the initial drug peak is 500 mcg/L, what is the drug level just before dose 31 is given? 250 mcg/L 500 mcg/L 1000 mcg/L 2000 mcg/L The trick as discussed in the VC, at plateau, the trough is ~ = initial dose peak; peak is 2x initial dose peak. Knowing this allows you to know peak and trough before or after any dose after plateau is reached. What Can Change the Kinetics of a Drug? (Kinetics) Food impact on Drug Absorption ↓ absorption Decreases rate Drug is kept in the stomach for a longer time Decreased extent Example: milk binds tetracycline, ﬁber binds digoxin ↑ absorption Some foods increase the absorption of a medication to increase its therapeutic e?ect High-calorie meal more than doubles the absorption of Invirase (saquinavir), a drug for HIV MODULE 01 VC 1 PART 3 Factors That Determine the Intensity of Drug Responses: DYNAMICS Pharmacodynamics: Impact of DRUGS ON THE BODY The drug must FIRST bind to a RECEPTOR Important concept!!! A DRUG-RECEPTOR INTERACTION must take place Important concept!!! A cellular response occurs BECAUSE of the DRUG-RECEPTOR INTERACTION Receptor A receptor is any functional macromolecule in a cell to which a drug binds to produce its e?ects Receptors can include enzymes, ribosomes, and tubulin The term receptor is generally reserved to refer to the body’s own receptors for hormones, neurotransmitters, and other regulatory molecules Drugs produce their therapeutic eNects by helping the body use its preexisting capabilities Types of Receptors (p. 48, Burchum & Rosenthal) First and Second Messengers Figure 2.9, p. 23, Norris (11th ed.) Porth’s Pathophysiology Factors That Determine the Intensity of Drug Responses: DYNAMICS Drug-receptor interaction Simple Occupancy Response is related to the number of receptors occupied Modiﬁed Occupancy The higher the aGinity of a drug to the receptor, the higher the potency The lower the aGinity of a drug to the receptor, the lower the potency FIG. 5.6 Model of simple occupancy theory, p. 50, Burchum & Rosenthal Factors That Determine the Intensity of Drug Responses: DYNAMICS Drug-receptor interaction Agonist Molecule that activates receptors Partial agonist Molecule that produces a response but not as great as an agonist Antagonist Molecule that blocks the activation of a receptor Interaction of Drugs with Receptors Under physiologic conditions, cardiac output can be increased by the binding of norepinephrine (NE) to receptors (R) on the heart. Norepinephrine is supplied to these receptors by nerves. These same receptors can be acted on by drugs, which can either mimic the actions of endogenous NE (and thereby increase cardiac output) or block the actions of endogenous NE (and thereby reduce cardiac output). Figure 5.3, p. 47, Burchum & Rosenthal, 12th ed. Dose-Response Relationships As the dosage increases, the response becomes progressively larger Treatment is tailored by increasing or decreasing the dosage until the desired intensity of response is achieved Very high maximal eNicacy is not always more desirable Maximum E?icacy & Relative Potency A ENicacy, or maximal e?icacy, is an index of the maximal response a drug can produce. The e?icacy of a drug is indicated by the height of its dose-response curve. In this example, meperidine has greater e?icacy than pentazocine. ENicacy is an important quality in a drug B Potency is an index of how much drug must be administered to elicit a desired response. In this example, achieving pain relief with meperidine requires higher doses than with morphine. We would say that morphine is more potent than meperidine. Note that, if administered in su?iciently high doses, meperidine can produce just as much pain relief as morphine. Potency is usually not an important quality in a drug. Receptor Binding The binding of a drug to its receptor is usually reversible Receptor activity is regulated by endogenous compounds When a drug binds to a receptor, it will mimic or block the action of the endogenous regulatory molecules and increase or decrease the rate of physiologic activity normally controlled by that receptor Receptors and Selectivity of Drug Action IMPORTANT CONCEPTS The more selective a drug is, the fewer side e?ects it will produce Receptors make selectivity possible Each type of receptor participates in the regulation of just a few processes Agonists – know the deﬁnitions – you will see this for the entire course Agonists are molecules that activate receptors Endogenous regulators are considered agonists Agonists have both a?inity and high intrinsic activity Example: Dobutamine mimics norepinephrine at cardiac receptors Agonists can make processes go “faster” or “slower” depending upon the eNect of the agonist on a particular cell Antagonists Do not cause receptor activation but cause pharmacologic eNects by blocking the activation of receptors by agonists VERY IMPORTANT CONCEPT If no is agonist present, an antagonist will have no observable e?ect Noncompetitive vs. Competitive Antagonists (see notes section) Noncompetitive antagonists Bind irreversibly to receptors Irreversible binding is equivalent to reducing the total number of receptors available for activation Reduce the maximal response that an agonist can elicit (fewer available receptors) Impact not permanent (cells are constantly breaking down “old” receptors and synthesizing new ones) Competitive antagonists Compete with agonists for receptor binding Bind reversibly to receptors Equal a?inity: Receptor occupied by whichever agent is present in the highest concentration Noncompetitive vs. Competitive Antagonists (Figure 5.7, Burchum & Rosenthal, p. 51, 12ed.) Interpatient Variability in Drug Responses Clinical implications of interpatient variability The initial dose of a drug is necessarily an approximation Subsequent doses must be “ﬁne-tuned” based on the patient’s response ED50* in a patient may need to be increased or decreased after the patient response is evaluated * ED50 – The e?ective dose for 50% of people Therapeutic Index—It’s Just a Number*! Measure of a drug’s safety Ratio of the drug’s LD50 (average lethal dose to 50% of the animals treated) to its ED50 (average e9ective dose to 50% of the animals treated) Since we are dealing with humans, we look at TD50 rather than the LD50 (It doesn’t look good if we kill 50% of our study patients!) The larger/higher the therapeutic index, the safer the drug The smaller/lower the therapeutic index, the less safe the drug *Actually, think of Therapeutic Index as a ratio. FIG. 5.9, p. 53, Burchum & Rosenthal Chapter 6: Drug Interactions 1.Discuss the consequences of drug-drug interactions, the basic mechanisms of drug-drug interactions, and the critical steps in minimizing adverse drug- drug interactions. 2.Focus on the liver as an example of a drug-metabolizing system and explain why it is such a crucial organ in many drug-drug interactions. 3.Discuss the e?ect of food on drug absorption, on drug metabolism (e.g., grapefruit juice), and on drug toxicity and action, as well as the timing of drug administration with respect to meals. Drug-Drug Interactions Intensiﬁcation of e?ects Increased therapeutic e?ects Sulbactam and ampicillin Increased adverse e?ects Aspirin and warfarin Reduction of e?ects Inhibitory: Interactions that result in reduced drug e?ects Reduced therapeutic e?ects Propranolol and albuterol Reduced adverse e?ects Naloxone to treat morphine overdose Pharmacokinetic Interactions Altered absorption – which factors ↑ absorption and which ↓ absorption Elevated gastric pH Laxatives Drugs that depress peristalsis Drugs that induce vomiting Adsorbent drugs Drugs that reduce regional blood ﬂow Pharmacokinetic Interactions Altered distribution Competition for protein binding Alteration of extracellular pH Altered renal excretion Drugs can alter: Filtration Reabsorption Active secretion Pharmacokinetic Interactions Altered metabolism Most important and most complex mechanism in which drugs interact Cytochrome P450 (CYP) group of enzymes Example of inducing agent: Phenobarbital Increase rate of metabolism two- to three-fold over 7 to 10 days Resolve over 7 to 10 days after withdrawal Inhibition of CYP isoenzymes Usually undesired Clinical Signiﬁcance of Drug-Drug Interactions Drug interactions have the potential to signiﬁcantly a?ect the outcome of therapy Responses may be increased or reduced The risk for serious drug interaction is directly proportionate to the number of drugs a patient is taking Interactions are especially important for drugs with low therapeutic indices Many interactions are yet to be identiﬁed Minimizing Adverse Drug-Drug Interactions Minimize the number of drugs a patient receives Take a thorough drug history Be aware of the possibility of illicit drug use Adjust the dosage when metabolizing inducers are added or deleted Adjust the timing of administration to minimize interference with absorption Be especially vigilant when a patient is taking a drug with a low therapeutic index Organ-Speciﬁc Toxicity Many drugs are toxic to speciﬁc organs Common examples include: Kidneys: Amphotericin B (antifungal) Heart: Doxorubicin (anticancer) Lungs: Amiodarone (antidysrhythmic) Inner ear: Aminoglycoside (antibiotic) Hepatotoxic Drugs Leading cause of liver failure in the United States More than 50 drugs are known to be hepatotoxic As some drugs undergo metabolism, they are converted to toxic products that can injure liver cells Combining hepatotoxic drugs may increase the risk for liver damage (e.g., acetaminophen and alcohol) Monitor aspartate aminotransferase (AST) and alanine aminotransferase (ALT) for liver injury Watch for signs of liver injury; educate patients about jaundice, dark urine, light- colored stools, nausea, vomiting, malaise, abdominal discomfort, and loss of appetite QT Interval Drugs: More Than 100 Are Known QT interval: Measure of the time required for the ventricles to repolarize after each contraction QT drugs: Drugs that prolong the QT interval on electrocardiography (ECG) Creates serious risk of life-threatening dysrhythmias Examples: Torsade's de pointes, ventricular ﬁbrillation Minimizing the risk: Most patients are at higher risk, including women, older adults, and patients with bradycardia, congestive heart failure (CHF), congenital QT prolongation, low potassium, and low magnesium (”I wish I had paid more attention in pathophysiology!”) Do not use two QT drugs concurrently Adverse Reactions to New Drugs Half of all new drugs have serious ADRs that are not revealed during Phase II and Phase III trials Drugs that are suspected of causing a previously unknown adverse e?ect should be reported to MedWatch, the FDA Medical Products Reporting Program Patients with chronic disorders are especially vulnerable to ADRs Boxed Warnings Also known as black box warnings Strongest safety warning a drug can carry and still remain on the market Purpose of this warning is to alert prescribers to: Potentially severe side e?ects (for example, life-threatening dysrhythmias, suicidality, major fetal harm) Ways to prevent or reduce harm (for example, avoiding a teratogenic drug during pregnancy) Example of a black box warning Pediatric Patients Children ARE NOT little adults ▪Ongoing growth and development ▪Di?erent age groups have di?erent challenges ▪ Two-thirds (66%)of drugs used in pediatrics have never been tested in pediatric patients ▪Twenty percent (25%) of drugs were ine?ective for children even though they were e?ective for adults ▪Thirty percent (30%) of drugs caused unanticipated side e?ects, some of which were potentially lethal Pharmacokinetics: Neonates and Infants Absorption Oral administration Gastric emptying time Prolonged and irregular Adult function at 6 to 8 months Gastric acidity Very low 24 hours after birth Does not reach adult values for 2 years Low acidity: Absorption of acid-labile* drugs is increased *Low acidity (higher pH) delays the breakdown certain drugs making the drug more easily absorbable. Pharmacokinetics: Neonates and Infants Distribution Protein binding Amount of serum albumin is relatively low Binding of drugs to albumin and other plasma proteins is limited in the infant Endogenous compounds compete with drugs for available binding sites Limited drug/protein binding in infants Reduced dosage are needed Adult protein binding capacity develops by 10 to 12 months of age Blood-brain barrier Not fully developed at birth Drugs and other chemicals have relatively easy access to the central nervous system (CNS) Infants especially sensitive to drugs that a?ect CNS function Dosage should also be reduced for drugs used for actions outside the CNS if those drugs are capable of producing CNS toxicity as a side e?ect Pharmacokinetics: Neonates and Infants Hepatic metabolism The drug-metabolizing capacity of newborns is low Neonates are especially sensitive to drugs that are eliminated primarily by the hepatic metabolism The liver’s capacity to metabolize many drugs increases rapidly about 1 month after birth The ability to metabolize drugs at the adult level is reached a few months later Complete liver maturation occurs by 1 year of age Renal excretion Signiﬁcantly reduced at birth Signiﬁcantly reduced at birth Low renal blood ﬂow, glomerular ﬁltration, and active tubular secretion Drugs eliminated primarily by renal excretion must be given in reduced dosage and/or at longer dosing intervals Adult levels of renal function achieved by 1 year Metabolism: Infants vs Adults Fig. 12.1 A. Plasma drug levels following IV injections. Dosage was adjusted for body weight. Note that plasma levels remain above the minimum e?ective concentration much longer in the infant. B. Plasma drug levels following sub- Q injection. Dosage was adjusted for body weight. Note that both the maximum drug level and the duration of action are greater in the infant. (p. 103, Burchum & Rosenthal, 12th ed.) Pharmacokinetics: Children One Year and Older Most pharmacokinetic parameters are like those of adults Drug sensitivity more like that of adults than for children younger than 1 year old One important diNerence: Children in this age group metabolize drugs faster than adults Markedly faster until the age of 2 years, then a gradual decline Sharp decline at puberty (Can you think of a reason why this might happen? See the notes!!!) May need to increase dosage or decrease interval between doses Adverse Drug Reactions Children are vulnerable to unique adverse e?ects related to organ immaturity and ongoing growth and development Age-related e?ects: Growth suppression (caused by glucocorticoids) Discoloration of developing teeth (tetracyclines) Kernicterus (sulfonamides) in neonates Promoting Adherence Provide patient/caregiver education in writing Dosage size and timing Route and technique of administration Duration of treatment Drug storage Demonstration techniques should be included as appropriate Drug Therapy in Geriatric Patients 1. Identify the main age-related physiologic, pathophysiologic, and pharmacologic factors that inﬂuence how older adults respond di?erently to drugs and state how those di?erences could (or likely will) a?ect drug responses. 2. Identify the most important factors that predispose older patients to adverse drug reactions. 3. Describe common reasons for noncompliance and nonadherence that are particularly relevant to older adults and list some approaches for minimizing those problems and improving compliance. Older Adult Patients The Beers Criteria When prescribing medications to older patients, it is important to check recommendations in the Beers Criteria→important to know about Altered pharmacokinetics More sensitive to drugs than younger adults and with greater variation in pharmacokinetics Multiple and severe illnesses Severity of illness, multiple pathologies Multiple-drug therapy Excessive prescribing Poor adherence Pharmacokinetics: Distribution Increased percentage of body fat Storage depot for lipid-soluble drugs Decreased percentage of lean body mass Decreased total body water Distributed in smaller volume; concentration increased and e?ects more intense Reduced concentration of serum albumin May be signiﬁcantly reduced in malnourished patients Causes decreased protein binding of drugs and increased levels of free drugs Pharmacokinetics: Metabolism Hepatic metabolism declines with age Reduced hepatic blood ﬂow, reduced liver mass, and decreased activity of some hepatic enzymes occur The half-lives of some drugs may increase, and responses are prolonged Responses to oral drugs (for example, those that undergo extensive ﬁrst-pass e?ect) may be enhanced Pharmacokinetics: Excretion Renal function undergoes progressive decline beginning in early adulthood (Another pathophysiology reference!) Reductions in renal blood ﬂow, glomerular ﬁltration rate, active tubular secretion, and number of nephrons Drug accumulation because of reduced renal excretion is the most important cause of adverse drug reactions in older adults Fig. 32.14 Relationship between the percentage of renal function and serum creatinine levels. (Norris, Porth’s Pathophysiology, 11h ed, p. 1104.) Pharmacokinetics: Excretion Renal function should be assessed with drugs that are eliminated primarily by the kidneys In patients who are older adults: Use creatinine clearance rather than serum creatinine to assess this, because lean muscle mass (source of creatinine) declines in parallel with kidney function (Remember module 05 last semester?) Creatinine levels may be normal even though kidney function is greatly reduced Summary of Pharmacokinetics in Older Adults (How much of this could you predict from Pathophysiology? I hope you are beginning to see how these courses are really coming together!) Increased Gastric pH ABSORPTION of Decreased absorptive surface area Decreased splanchnic blood ﬂow Drugs Decreased GI motility Delayed gastric emptying Increased body fat DISTRIBUTION of Decreased lean body mass (LBM) Decreased total body water Decreased Drugs serum albumin Decreased cardiac output (CO) METABOLISM of Decreased hepatic blood ﬂow Decreased hepatic mass Drugs Decreased activity of hepatic enzymes Decreased renal blood ﬂow EXCRETION of Decreased glomerular ﬁltration rate (GFR) Decreased tubular secretion Drugs Decreased number of nephrons Pharmacodynamic Changes in Older Adult Patients Alterations in receptor properties may underlie altered sensitivity to some drugs Drugs with more intense e?ects in older adults Warfarin and certain central nervous system depressants Beta blockers less eNective in older adults, even in the same concentrations Reduction in number of beta receptors Reduction in the a?inity of beta receptors for beta-receptor blocking agents Adverse Drug Reactions (ADRs) 7x more likely in the elderly Account for 16% of hospital admissions Account for 50% of all medication-related deaths Majority are dose related rather than idiosyncratic* Symptoms in older adults often nonspeciﬁc May include dizziness and cognitive impairment *What does this word mean? Factors That Contribute to Poor Adherence in Older Adults (Much of this is intuitive but some are surprising.) Multiple chronic disorders Multiple prescription medications Multiple doses per day for each medication Drug packaging that is di?icult to open Multiple prescribers Changes in the regimen (addition of drugs, changes in dosage size or timing) Cognitive or physical impairment (reduction in memory, hearing, visual acuity, color discrimination, or manual dexterity) Factors That Contribute to Poor Adherence in Older Adults (Much of this is intuitive but some are surprising.) Consider the social determinants of health that a?ect populations Living alone Recent discharge from hospital Low literacy Inability to pay for drugs Personal conviction that a drug is unnecessary or the dosage too high Presence of side e?ects Promoting Adherence with Unintentional Nonadherence Simpliﬁed drug regimens Clear and concise verbal and written instructions based on the health literacy of the patient* Appropriate dosage form Clearly labeled and easy-to-open containers Daily reminders Support system Frequent monitoring * This is why “TEACHING POINTS” are important. Time Course of Drug Responses (Kinetics) After repeated doses –highest level→ peak –lowest level→ trough Fluctuation reduction –continuous infusion –administer depot prep –reduce dose size and decrease time of dose frequency At At Why is the concept of peak and trough important? plateau, plateau, (Think about your clinical experience.) Initial trough ~ = peak is 2x MEMORY TRICK→ peak initial peak initial peak 2 gms 2 gms 4g gms Time Course of Drug Responses (Kinetics) Antimicrobial Therapy Used to treat infectious diseases 190 MILLION doses of antibiotics are given in hospitals EACH DAY Modern antimicrobials: 1930’s and 1940’s Signiﬁcantly reduced morbidity and mortality from infection Antimicrobial Therapy: General Terms Antimicrobial therapy is CHEMOTHERAPY Antimicrobial Any agent that harms a microbe Antibiotic Any substance produced by a microbe that may harm another microbe Anti-infective Any agent that reduces or eliminates infection Antibiotic Antiviral Chicken soup Cranberry juice Basic Principles of Antimicrobial Therapy Selective Toxicity – kills the “bug” not the host. Can be achieved in three ways: 1. Disruption of the bacterial cell wall (ex. penicillin) 2. Disruption of bacterial protein synthesis (ex. clindamycin) 3. Inhibition of an enzyme unique to bacteria (ex. sulfonamides) Classiﬁcation of Antimicrobials There are two ways to classify antimicrobials Mechanism of action (see Table 88-2, p. 1086 Burchum & Rosenthal) Cell wall inhibitors Cell membrane “disruptors” Protein synthesis (lethal vs non-lethal) Nucleic acid (DNA/RNA) synthesis Antimetabolites Susceptible organisms (see Table 88-1, p. 1085-6 Burchum & Rosenthal) Gram Positives Gram Negatives Resistant/non-resistant organisms It is important to understand both classiﬁcation systems because this allows therapy that is speciﬁc to the organism being treated Classiﬁcation of Antimicrobials IMPORTANT CONCEPT Bacteriostatic drugs can slow bacterial growth but do not cause bacterial death Bactericidal drugs are directly lethal to bacteria Animal vs Bacterial Cell Note the di?erences: There are many Innate Resistance to Antimicrobial Therapy Microbes have four primary mechanisms of drug resistance 1. Reduction of drug concentration decrease the amount of drug that enters the cell 2. Alteration of target molecules change molecular structure in receptors to prevent drug-receptor interaction 3. Antagonist production may produce a compound that antagonizes the drug 4. Drug inactivation develop enzymes that inactivate and drug which prevents harm to the cell Acquired Resistance to Antimicrobial Therapy Spontaneous mutation: produces random change in microbe DNA; this is usually a slow process producing resistance to a speciﬁc drug Conjugation: primarily in Gram-negative organisms; DNA is transferred from one bacteria to another; DNA from donor cell and recipient cell produces resistance to multiple drugs How Do Antibiotics Promote Resistance Drugs make conditions favorable for the overgrowth of microbes that have acquired mechanisms for resistance Broad-spectrum agents do the most to facilitate the emergence of resistance The more that antibiotics are used, the faster drug-resistant organisms emerge ANTIBIOTIC STEWARDSHIP IS IMPORTANT!!! Terms To Know Nosocomial infections Health care–associated infections (HAI) Superinfection New infection: appears during treatment for a primary infection Superinfections: caused by drug-resistant organisms that are often di?iculty to treat Basic Principles of Antimicrobial Therapy Selection of the appropriate antibiotic Identify the organism Culture and sensitivity Consider the drug sensitivity of the organism Consider host factors Immunocompromised vs otherwise healthy patient – why is this important????? Some drugs may be eliminated because of: Drug allergy Inability to penetrate site of infection Other patient variables Renal disease Hepatic disease Empiric Therapy Empiric Therapy Antibiotic therapy before causative organism is positively identiﬁed Drug selection based upon: Clinical evaluation (NUR 614 next semester) history and physical exam Knowledge of microbes most likely to have caused the infection Other Factors to Consider Host defenses A competent immune system is necessary for the antimicrobial action of some drugs Site of infection Can the drug get to where it needs to get to (kinetics)??? Example: Antimicrobials may not penetrate an abscess very well Previous drug reactions Genetic factors Some drugs cannot be used because the patient may have a genetic make-up that when exposed to a certain drug, the patient will have an adverse reaction; some patients are genetically rapid metabolizers of certain drugs Example: A patient with G6PD deﬁciency given a sulfonamide will experience hemolysis of their red cells Dosage Size and Duration The antimicrobial agent must be present: At the site of infection (Kinetics→ Distribution) For a su?icient length of time (Kinetics→ Metabolism and Excretion) Patient education is important Antibiotics must not be discontinued prematurely What might be the e?ect(s) of prematurely discontinuing medication? Combination Therapy Antibiotic combinations can be Additive (1+1 = 2) Synergistic (potentiation 1 + 1 > 2) Antagonistic (1 + 1 < 2) Indications Mixed infections Prevention of resistance May prevent toxicity Enhanced antibacterial action Disadvantages Possible toxic or allergic interactions Risk of superinfection Increased cost May potentiate drug resistance (that is counter to what is stated above) Possible antagonistic (as mentioned above) Prophylactic Use of Antimicrobials PROPHYLAXIS: administered BEFORE a procedure to prevent, not treat infection INDICATIONS Surgery Reduces the risk of post-op infection Bacterial endocarditis For patients with known heart defects, ABX are used before certain procedures known to increase bacterial shedding: extensive dental work may be an example Neutropenia For patients who are immunocompromised for whatever reason (chemotherapy, congenital immune deﬁciencies, AIDS, etc.), risk of infection may be reduced (note: reducing risk not treating a speciﬁc condition); risk of fungal infection increases in this circumstance Other indications Inﬂuenza protection with antivirals, chronic urinary tract infections, Pre-Exposure Prophylaxis (PreP) such as travel to countries of endemic disease (ex.: malaria) Inappropriate Use of Antimicrobials Improper/inadequate dosing Treatment of fever of unknown origin (FUO) Do you remember the deﬁnition of FUO from NUR 612? Treatment in the absence of adequate bacteriologic information Empiric therapy should be used only in life-threatening circumstances The antimicrobial must get to the site of infection→ drain the abscess if present Do not use ANTIBIOTICS for VIRAL INFECTIONS Inappropriate Use of Antimicrobials Do not use ANTIBIOTICS for VIRAL INFECTIONS Improper or inadequate dosing Treatment of fever of unknown origin (FUO) Treatment in the absence of adequate bacteriologic information Empiric therapy should be used only in life-threatening circumstances The antimicrobial must get to the site of infection→ drain the abscess if present VC 2 PART 2 Penicillins: What to Study First use the slides as your outline Look at the tables and graphs as instructed Consider ampicillin as the PCN prototype Read: BRAOD/EXTEND-SPECTURM PCNs (Aminopenicillins) ampicillin/amoxicillin (p.1105 Burchum & Rosehthal 12th ed.) Read: Key Points and Summary of Major Nursing Implications (pp. 1106-7 Burchum & Rosenthal 12th ed.) Understand the major bacteria treated with PCN-type drugs Objectives 1. Describe the mechanism of action of beta-lactam antibiotics. 2. Describe the mechanisms of bacterial resistance (this is also found in the Introduction to Antimicrobial Therapy). 3. Explain how beta-lactamase inhibits the function of PCN. 4. Describe the di?erent therapeutic spectra of PCN G and V, Penicillinase-resistant PCNs, Broad- spectrum PCNs, Extended-spectrum PCNs, and PCNs combined with beta-lactamase inhibitors. 5. Explain distribution of the PCN drugs and associated barriers. 6. Describe the types of allergic reactions that can occur with PCNs and the possible time of onset. 7. Describe alternative therapeutic options for patients with PCN allergies. 8. Describe the function of beta-lactamase inhibitors and explain their therapeutic importance. 9. Describe the metabolism of PCNs 10. Explain the signiﬁcance of renal disease on excretion of PCNs 11. Describe possible dosing changes in patients with renal disease The Penicillins (PCNs): General Concepts Active against a variety of bacteria Generally, toxicity is low Principle adverse e?ect: Allergy All of the PCNs contain a beta-lactam ring Other antibiotics also contain a beta-lactam ring (Cephalosporins, monobactams, carbapenem, and others. More on this later!) The pictures are for comparison only!!! Don’t learn the structure. The Penicillins: How do they work? Mechanism of action Weaken the cell wall→ bacteria takes up excessive water and ruptures Active ONLY against bacteria undergoing growth and division BACTERICIDAL Bacterial resistance occurs in several ways: Inability of PCNs to reach their target Inactivation of PCNs by bacterial enzymes Production of penicillin-binding proteins (PBPs) that have a low a?inity for the penicillins Remember what was said earlier about receptors and a4inity for other molecules The Penicillins: How do they work? Penicillin→ Targets Penicillin Binding Proteins (PCBs) Inhibition of transpeptidases Transpeptidases are necessary to form crosslinks in cell wall Activation of autolysins Autolysins cleave bonds in the cell wall The 𝛃-lactam ring FIG. 89.1 Inhibition of transpeptidase by penicillins. The bacterial cell wall is composed of long strands of a peptidoglycan polymer. As depicted, transpeptidase enzymes create cross-bridges between the peptidoglycan strands, giving the cell wall added strength. By inhibiting transpeptidases, penicillins prevent cross-bridge synthesis and thereby weaken the cell wall. The Cell Envelope Gram-positive cell envelope Only two layers Relatively thick cell wall that is easily penetrated Gram-negative cell envelope Three layers Thin cell wall and an additional outer membrane: di?icult to penetrate Classiﬁcation of Penicillins Narrow-spectrum Penicillinase sensitive: penicillin G, penicillin V Narrow-spectrum Penicillinase resistant: nafcillin, oxacillin, dicloxacillin Broad-spectrum Aminopenicillins: ampicillin, amoxicillin Extended-spectrum Antipseudomonal: ticarcillin, piperacillin Did you notice that all of the above drugs ended in -CILLIN? Drug Resistance Beta-lactamases Enzymes that break the beta-lactam ring Penicillin and other beta-lactam antibiotics (ABX) are rendered ine?ective Synthesized by Gram-positive and Gram-negative bacteria If speciﬁc to PCNs, they are known as penicillinases Altered penicillin-binding-proteins (PCBs) Seen in methicillin-resistant Staph aureus (MRSA) Inhibits binding of PCN to bacterial cell wall See BOX 89.1 p. 1102 (Burchum & Rosenthal, 12th ed.) Read about MRSA Principle Adverse Events Allergy to PCN-like drugs Anaphylactic reactions occur more frequently with the penicillins than with any other drug. Type I Hypersensitivity: Anaphylaxis IgE mediated (NUR 612 rears its ugly head again!) Immediate: 2–30min Accelerated: 1–72hours Type IV Hypersensitivity Delayed: days to months If patient has previous anaphylaxis, the PCN-like drugs are contraindicated If patient has had rash, CEPHALOSPORINS are acceptable option Observe patients for 30 minutes following administration of PCN-like medications Drug Interactions Aminoglycosides Do not mix PCNs and aminoglycosides in same IV solution (PCN inactivates the aminoglycoside) Give PCNs and aminoglycosides several hours apart to provide maximal e?ect of both drugs Probenecid Delays renal excretion of PCNs by competing with excretion transport in kidney Use with caution in renal disease PCN and bacterioSTATIC drugs are not used together Why??? Put on your “critical thinking cap” here. Other PCN-type Drugs Penicillinase-resistant PCNs Nafcillin, oxacillin, dicloxacillin Broad-spectrum penicillins Ampicillin, amoxicillin Common side e?ects Rash Diarrhea Antipseudomonal PCNs Ticarcillin, piperacillin E?ective against organisms susceptible to the aminopenicillins plus Pseudomonas aeruginosa, Enterobacter species, Proteus (indole positive), Bacteroides fragilis, and many Klebsiella species PCN Combinations Beta-lactamase inhibitors Clavulanic acid, tazobactam, sulbactam Extends antimicrobial spectrum when combined with penicillinase- sensitive antibiotics Ampicillin/sulbactam [Unasyn®]* Amoxicillin/clavulanic acid [Augmentin®] Ticarcillin/clavulanic acid [Timentin®] Piperacillin/tazobactam [Zosyn®] *Trade names will not be used for exam purposes. PCN: Pharmacokinetics Absorption – remember your clinical experience with these ABX PCN G: IM, IV (unstable in acidic environment – NOT given PO) PCNV: PO Ampicillin: PO, IV Amoxicillin: PO Amoxicillin/clavulanate*: PO Nafcillin, oxacillin: IV Ampicillin/sulbactam*, ticarcillin/clavulanate*, piperacillin/tazobactam*: IV Be aware of sodium overload with large doses of ticarcillin Beta-lactamase inhibitor combination drugs PCN: Pharmacokinetics Distribution Distributes well to most tissues In absence of inﬂammation, poor penetration of meninges, joints, and eyes In presence of inﬂammation, penetration of meninges, joints, and eyes is increased Metabolism Minimal Excretion Active tubular excretion (90%); glomerular ﬁltration (10%) With renal disease, half-life(T1/2)is increased. WHY???Again, use your “critical thinking cap” for the answer. Beta-Lactams: Drugs That Weaken the Cell Wall Chapter 89 Cephalosporins, Carbapenems, Vancomycin, and Aztreonam Cephalosporins and others: What to Study First use the slides as your outline Look at the tables and graphs Consider prototypes Read: Therapeutic Uses in Burchum and Rosenthal (p. 1110, 12th ed.) Read: C. di^icile infection and Adverse E^ects (vancomycin) in Burchum and Rosenthal Read: Key Points, and Summary of Major Nursing Implications Understand the di?erences in the ﬁve cephalosporin generations and what the indications for each are Objectives (Notice that many of these are similar to PCNs; work smart not hard.) 1. Describe the mechanism of action of beta-lactam antibiotics. 2. Describe the mechanisms of bacterial resistance (this is also found in the Introduction to Antimicrobial Therapy). 3. Explain how beta-lactamase inhibits the function of cephalosporins. 4. List the cephalosporins that are not resistant and are resistant to beta-lactamases 5. Describe the di?erent therapeutic spectra of the di?erent generation cephalosporins. 6. Explain distribution of the of the di?erent generation cephalosporins. 7. Describe the types of allergic reactions that can occur with cephalosporins and the possible onset time. 8. Describe therapeutic options with cephalosporins for patients with PCN allergies. 9. Describe the important drug-drug interactions with cephalosporins. 10. Describe the metabolism of cephalosporins 11. Explain the signiﬁcance of renal and hepatic disease on excretion of cephalosporins. 12. Describe possible dosing changes in patients with renal disease. The Cephalosporins: General Concepts (Notice the similarities to the PCNs) Active against a variety of bacteria Generally, toxicity is low Principle adverse e?ect: Allergy (although risk with cephalosporins is very low) All the cephalosporins contain a beta-lactam ring Other antibiotics also contain a beta-lactam ring, too. (Monobactams and carbapenem but NOT vancomycin) The pictures are for comparison only!!! Don’t learn the structure. The Cephalosporins They all begin with cef Mechanism of action: The same as the PCNs→ binds to penicillin-binding proteins (PBPs) Activates autolysins that cleave bonds in the cell wall Weaken the cell wall→ bacteria takes up excessive water and ruptures Active ONLY against bacteria undergoing growth and division BACTERICIDAL How are these like the penicillins? Cephalosporins Five generations of cephalosporins are available With each successive generation, there is: Improved resistance to beta-lactamase with 3rd, 4th, and 5th generations Increased activity against Gram-negative bacteria and anaerobes (this is important to know) Increased ability to penetrate the cerebrospinal ﬂuid (CSF) Toxicity is very low Major DiNerence Between Cephalosporin Generations Table 90.1, p. 1108, Burchum & Rosenthal, 12th ed. rarely drugs of choice for active infections Cephalosporins: Therapeutic Uses (When learning, generalize and then know the exceptions) First generation Gram-positives: E?ective against staphylococci (NOT MRSA) and non-enterococcal streptococci Useful for prophylaxis for surgical site wound infection (see Chapter 88, p. 1069, SURGERY, in Burchum & Rosenthal, 12th ed.) – Ask your orthopedic surgeon friends about Ancef® (cefazolin) Second generation Gram-positives Slight Gram-negative activity – not generally used, however for Gm neg infections NO ACTIVITY against Pseudomonas aeruginosa NOT e?ective in the CSF Third generation Increased resistance to beta-lactamase Increased activity against Gram-negatives Ceftazidime has activity against P. aeruginosa Clinically e?ective in the CSF Cephalosporins: Therapeutic Uses (When learning, generalize and then know the exceptions) Fourth generation There is only one available; very broad spectrum Highly active against against P. aeruginosa Very e?ective in the CSF Fifth generation There is only one available Similar to third generation Only cephalosporin active against MRSA NOTE: Fourth and ﬁfth generation cephalosporins have VERY SPECIFIC USES and are, in most circumstances, used only after appropriate infectious disease consultation. Cephalosporins: Kinetics Absorption PO – 10 products available: GI absorption not great but serum levels are still useful IV or IM – 8 products available PO, IV, IM - cefuroxime Distribution Most body tissue and ﬂuids except the eye Generations 1 and 2 unreliable to the CSF Elimination All are eliminated by the kidney EXCEPT ceftriaxone (IV, IM) Cephalosporins: Adverse ENects Allergies Rash most common; develops 2 – 5 days after exposure Severe reactions are uncommon Only 1% of the 0.004 – 0.04% of patients who have anaphylaxis to PCN will have serious reaction to cephalosporins (This is very low but important) Less common with 3rd – 5th generations For patients who have had RASH with PCN, cephalosporins are acceptable DO NOT USE CEPHALOSPORINS IF PATIENT HAS HAD ANAPHYLAXIS WITH PCN Bleeding with cefotetan and ceftriaxone Monitor PT/PTT Use with caution in patients who use aspirin/NSAIDS or who are on anticoagulant therapy Thrombophlebitis Occasionally seen with all ABX – rotate sites Cephalosporins: Drug Interactions Probenecid Delays the excretion of some cephalosporins This is the same as for PCN Alcohol Cefazolin and cefotetan induce alcohol intolerance Causes nausea and vomiting (disulﬁram e?ect similar to metronidizole) DO NOT USE WITH ALCOHOL Calcium I am generalizing here: Do not use cephalosporins with calcium containing ﬂuids either together in the same ﬂuid or in the same line. This is particularly important IN NEONATES. Not necessarily an issue in diNerent lines. Carbapenems They all end in penem Beta-lactam (you should now know how they work) Very broad spectrum EXCEPT MRSA Only used parenterally To prevent resistance, use only when other narrow spectrum drugs cannot be used (allergy, drug resistance) Carbapenems Imipenem Highly active against Gram-positive cocci Gram-negative cocci and rods Most e?ective beta-lactam against anaerobic bacteria Useful for mixed infections Not absorbed from the GI tract Distributed to body ﬂuids, tissues and the CSF Excreted by KIDNEY A ﬁxed dose of cilistatin is added imipenem to inhibit renal destruction of imipenem by renal enzymes – this increases urinary concentration of imipenem Imipenem: Other Information Adverse e?ects Nausea, vomiting, and diarrhea Superinfections and fungal infection in ~4% of patients Seizures (rare) Allergies Rash, pruritus, fever Rare cross-sensitivity in patients allergic to PCN (~1%) Drug interactions Valproate (used to control seizures) Imipenem reduces valproate levels Use with valproate only if other drugs are not appropriate Additional seizure precautions are necessary. WHY??? Vancomycin NOT a beta-lactam but inhibits cell wall production Most widely used antibiotic in US hospitals Primary indication C. di^icile see Recommended Treatments (p. 1114 )more on this when we get to the GI module MRSA Treatment of serious infections with susceptible organisms in PCN allergic patients Vancomycin: KINETICS/Adverse Events Poor GI absorption (PO used only for GI infections such as C. di^) When given IV, MUST BE GIVEN VERY SLOWLY (over 60 minutes) to prevent Vancomycin Flushing Syndrome (VCS) previously called “Red Man Syndrome” ﬂushing, rash, pruritus, urticaria [blotchy skin], tachycardia, and hypotension) Distributed to most tissues Unreliable distribution into the CSF Excreted by KIDNEY Must modify dose with renal impairment Vancomycin: Adverse Events Ototoxicity Rare but increased in renal impairment and concurrent use of other ototoxic drugs such as the aminoglycosides (gentamicin) Possibly reversible Thrombophlebitis common Use dilute solutions and administer slowly (see previous slide) Change sites often Rarely, immune-mediated thrombocytopenia Platelets must ﬁrst bind to vancomycin THERE IS NO CROSS REACTIVITY TO PCN – this property makes this drug VERY useful Aztreonam A Monobactam NOT a beta-lactam but inhibits cell wall production Highly resistant to beta-lactamase Narrow spectrum Active ONLY against Gram-negative aerobic bacteria Neisseria H. inﬂuenza P. aeruginosa Enterobacteriaceae E. coli Klebsiella Proteus Serratia Salmonella Aztreonam: Kinetics No GI absorption IV, IM INHALED (used to treat pulmonary P. aeruginosa) Distributed to most body tissues/ﬂuids including the CSF Excreted unchanged by the kidney Must modify dose with renal impairment Aztreonam: Adverse Events Pain at injection site Thrombophlebitis SAFE FOR PCN ALLERGIC PATIENTS VC 2 PART 3 Drugs for the Ear:Acute Otitis Media, Otitis Externa, and Otomycosis CHAPTER 111 Drugs for the Ear: Objectives 1. Describe the anatomy of the external auditor canal, the middle ear, and the inner ear. 2. Explain the function of the Eustachian tube 3. Identify the primary organisms that cause acute otitis media (AOM) 4. Describe the natural history of AOM 5. Describe the diagnostic criteria for AOM 6. Explain the di?erences in the therapeutic management of AOM in the infant < 6 months old, the 6- month to 2-year-old, and the child older than 2 years old. 7. Describe the recommend antibacterial drugs for AOM based upon severity of illness or history of drug allergy. 8. Describe the changes in ABX therapy if no improvement is seen in 48-72 hours following initial therapy. 9. Describe the therapy for otitis media with e?usion. 10. Describe the etiology, signs, and symptoms of acute otitis externa (AOE). 11. Describe two routes of treatment of AOE and list the medications used for each. 12. Describe the therapeutic options for AOE if the tympanic membrane is ruptured. 13. Identify the at-risk populations for necrotizing otitis externa (NOE) 14. Discuss treatment options for NOE 15. Identify the organisms that cause fungal otitis externa and describe the treatment options. Anatomy of the Ear External ear – collects sound waves Auricle (pinna) External auditory canal (EAC) Middle Ear – transmits sound from tympanic membrane to inner ear Eustachian tube – connects the middle ear to the nasopharynx Malleus Incus Stapes Inner ear Semicircular canals - balance Cochlea - hearing Mucociliary system transports bacteria from middle ear to nasopharynx Normal vs Abnormal Tympanic Membranes (TM) A. Normal TM B. TM with mild bulging C. TM with moderate bulging D. TM with severe bulging Inﬂammation Acute Otitis Media (AOM) Inﬂammation of the middle ear Characteristics Fluid in the middle ear Otalgia – children may tug on a?ected ear Etiology Bacterial Viral Usually begins as viral infection in the nasopharynx Diagnosis – must have all three Acute onset Middle-ear e?usion Middle-ear inﬂammation E?usion in Middle Ear Primary Pathogens – what you will treat Streptococcus pneumonia 15-25%* Haemophilus inﬂuenza 50-60% Moraxella catarrhalis 12-15% Group A Streptococcus 2-10% No bacteria found 10-30% Others Uncommon (e.g., Streptococcus pyogenes, Staphylococcus aureus, gram-negative bacilli) Respiratory viruses with or without bacteria 66% https://www-uptodate-com.uab.idm.oclc.org/contents/acute-otitis-media-in-children-epidemiology-microbiology-and- complications?search=acute-otitis-media-in- children-epidemiology-microbiology- andcomplications&source=search_result&selectedTitle=1~15 0&usage_type=default&display_rank=1 Literature review current through: July 2024.Accessed August 22, 2024 Standard Treatment of Acute Otitis Media AOM requires analgesia Acetaminophen Ibuprofen SOME should receive ABX when indicated 80% of AOM resolves spontaneously without ABX Observe for 48-72 hours – This is hard for most parents to accept!!!!!!!!!!!!!!!!!!!!!!!!!!! THERE ARE EXCEPTIONS TO THIS RULE – see following slides If symptoms persist or get worse, begin antibacterial therapy Therapy vs Observation Criteria for Choosing Initial Antibacterial Therapy Versus Observation in Children with AOM Management Recommendation Age Certain Diagnosis Uncertain Diagnosis Less than 6 Antibacterial therapy Antibacterial therapy months Antibacterial therapy if illness is severe; 6 months to 2 years Antibacterial therapy observation if illness is not severe* Antibacterial therapy if illness is severe; Observation, regardless of symptom 2 years and older observation if illness is not severe* severity * Severe illness = moderate to severe otalgia or fever of 39o C (102.2oF) or higher; non- severe illness= mild otalgia and fever below 39oC in the past 24 hours Treatment of AOM Acute otitis media (AOM) High-dose amoxicillin Antibiotic-resistant otitis media High-dose amoxicillin-clavulanate Prevention Breast-feeding for at least 6 months Avoiding childcare centers when respiratory infections are prevalent Eliminating exposure to tobacco smoke Reducing paciﬁer use in the second 6 months of life Avoiding supine bottle feeding (bottle propping) Vaccination for and treatment of inﬂuenza Vaccination against Streptococcus pneumoniae Patient Group and Recommended Drugs (See the SANFORD GUIDE) Illness Severity For Most Patients For Patients with Penicillin Allergy (note the type of allergy) Patients Receiving Immediate Antibiotic Therapy Non–type I allergy: Cefdinir, 14 mg/kg/day in 1 or 2 divided doses or Cefuroxime, 15 mg/kg twice daily or Cefpodoxime, 5 mg/kg twice daily Non-severe Amoxicillin, 40–45 mg/kg Type I allergy (anaphylaxis): illness twice daily Azithromycin, 10 mg/kg on day 1, then 5 mg/kg on days 2, 3, 4, and 5 or Clarithromycin, 7.5 mg/kg twice daily Clindamycin, 20 to 30 mg/kg/day in 3 doses Amoxicillin, 45 mg/kg twice Ceftriaxone, 50 mg/kg IM for 1 or 3 days (if non-Type I Severe illness daily plus clavulanate, penicillin allergy) 3.2 mg/kg twice daily Patients with Persistent Symptoms After 48–72 hr of Observation (with No Antibiotic Therapy) Same as for patients receiving immediate antibiotic therapy Patients with Persistent Symptoms After 48–72 hr of Antibiotic Therapy (Indicating Drug Resistance) Amoxicillin, 45 mg/kg Non–type I allergy: Non-severe twice Ceftriaxone, 50 mg/kg IM or IV for 3 days illness daily plus clavulanate, Type I allergy (anaphylaxis): 3.2 mg/kg twice daily Clindamycin, 30–40 mg/kg/day in 3 divided doses Ceftriaxone, 50 mg/kg IM Clindamycin (plus a third-generation cephalosporin if Severe illness for 3 days non–type I penicillin allergy), tympanocentesis Alternatives for Children with SEVERE RXNs Alternatives§ for Children with Severe Reaction* to Beta-lactams Including Cephalosporins Antibiotic Route Dose Maximum Daily Dose Azithromycin Oral 10 mg/kg on day 1 then 5 mg/kg days 2 through 6 500 mg day 1 250 mg days 2-6 Clarithromycin𝛟 Oral 15 mg/kg/day in 2 doses 1 g/day Clindamycin Oral 20 to 30 mg/kg/day in 3 doses 1.8 g/day § Other alternatives may exist. Check the Sanford Guide for other possibilities. * For children who have received a beta-lactam antibiotic (eg, penicillins, cephalosporins) in the previous 30 days or have concomitant purulent conjunctivitis or have a history of recurrent otitis media unresponsive to amoxicillin. 𝛟 Infrequently used because of drug interactions. Recurrent Otitis Media Acute otitis media that occurs 3 or more times within 6 months, or 4 or more times within 12 months Short-term antibacterial therapy Prophylactic antibacterial therapy Prevention and treatment of inﬂuenza Tympanostomy tubes Otitis Media with ENusion (OME) Often seen after AOM episode Fluid in middle ear without local or systemic illness May cause mild hearing loss but no pain Antibiotics have minimal eNect ‒ do not use Serous eNusion Otitis Externa Acute otitis externa (OE) (“swimmer’s ear”) Bacterial infection of the EAC Abrasion and excessive moisture Topical treatment 2% solution of acetic acid + alcohol as ear drops What if the tympanic membrane is ruptured? Unlike many otic preparations, ﬂuoroquinolones and ﬂuoroquinolone/corticosteroid combinations are safe for patients who have perforated tympanic membranes Ciproﬂoxacin plus hydrocortisone, ciproﬂoxacin plus dexamethasone, and oﬂoxacin alone Oral treatment indicated if infection extends beyond the EAC Adults: Ciproﬂoxacin Children: Cephalexin (do not use quinolones in children < 18 years) Necrotizing (Malignant*) Otitis Externa Rare complication of AOE Elderly, diabetic/immunocompromised patients Bacterial invasion of the mastoid bone Pseudomonas aeruginosa is common pathogen Treat with anti-pseudomonal meds Oﬂaxicin drops Ciproﬂoxin tablets If severe, IV imipenem/cilastatin Duration of treatment: 4-6 weeks *In this instance, malignant means aggressive not cancer. Necrotizing (Malignant*) Otitis Externa (NOE) Presentation of NOE Headache Fever Otorrhea Mastoid tenderness (Griesinger sign) Consequences of NOE Invasion of the mastoid or temporal bone can result in damage to the cranial nerves IX, X, and XI If the infection erodes through the bone, meningitis can result Lateral sinus thrombosis is potentially fatal Fungal Otitis Externa (Otomycosis) 10% of OE caused by fungi, not bacteria Two most common pathogens: Aspergillus: 80% to 90% Candida Intense pruritus and erythema with or without pain or hearing loss Managed with thorough cleansing and acidifying drops 1% clotrimazole used if acidifying drops are not e?ective Complementary and Alternative Therapy**Chapter 87***The Important Concepts Complementary and Alternative Therapy Everything you need to know for this chapter is in the PowerPoint presentation Use the text only if you want more information Please do not assume any instructor bias either FOR or AGAINST the use of Complementary and Alternative Therapy→ Knowledge is Truth! Objectives 1. Deﬁne complementary and alternative therapy. 2. Describe the purpose of supplements 3. Explain how supplements are or are not regulated 4. For the supplements listed, explain the important side e?ects that may be harmful to a patient (This information is highlighted in RED) 5. List the four (4) supplements that should be avoided and explain why Alternative Therapy: What? Complementary and alternative medicine (CAM) treatment practices that are not widely accepted or practiced by mainstream clinicians in a particular culture Examples: prayer, homeopathy, massage, mind-body techniques, therapeutic touch, acupuncture, and treatment with vitamins, minerals, nonvitamin/nonmineral products (e.g., herbal products), and other natural remedies Dietary supplements “vitamins, minerals, herbs and other botanicals, amino acids, and substances such as enzymes, organ tissues, glandulars, and metabolites” intended to supplement the diet Alternative Therapy: Why? Perception that supplements are safer and “healthier” than conventional drugs Sense of control over one's care Emotional comfort from taking action Cultural inﬂuence Limited access to professional care Lack of health insurance Convenience Media hype and aggressive marketing Recommendation from family and friends Regulation of Dietary Supplements Conventional drugs (Rx and OTC) require rigorous evaluation before release Botanicals, vitamins and minerals are categorized as “supplements” Supplements do not require the same evaluation as Rx and OTC medications Why is this a problem Many supplements can have harmful interactions with Rx and OTC medications Increased e?ectiveness (toxicity) or decreased e?ectiveness Regulation of Dietary Supplements Dietary Supplement Health and Education Act of 1994 (DSHEA) restrictions: Package labeling – must be labeled as “supplements” Manufacturers can “insinuate” but not make claims Yes: “promotes”, “helps”, “reduces”, “maintains” Must state: “This product is not intended to diagnose, treat, cure, or prevent any disease.” No: “cures”, “improves”, “lowers”, “protects”, “relieves”, and others (see p. 1068,) Adverse e?ects – manufacturer is responsible for safety Impurities, adulterants, and variability – not addressed→ dangerous products have reached the general population Ephedra, lead, mercury, arsenic not found until AFTER release We should always ask our patients: “Which product would I be more comfortable using—one that has been tested for adverse e?ects before I take it, or one that is evaluated for adverse e?ects only after it caused me harm?” Herbal Product Standardization There is often uncertainty about the amounts of active ingredients - multifactorial Standardization is di?icult with many herbal products Table 87. 2, p. 1069, Burchum & Rosenthal (12th ed.) Common Supplements ALWAYS TAKE A CAREFUL AND COMPLETE DRUG HISTORY* Ask about herbals...patients do not think of these as DRUGS Particularly important before surgery→ stop all herbals 2 weeks before Black Cohosh Commonly used to treat menopausal symptoms Mechanism of action is unknown May be e?ective as estrogen; long-term use not evaluated May potentiate antihypertensives Coenzyme Q-10 (CoQ-10) Potent antioxidant participates in production of adenosine triphosphate (ATP) at the mitochondrial level Commonly used for encephalomyopathies, CHF, and statin induced myopathies Possible GI disturbance *Patients do not always think of supplements as medications. Common Supplements Cranberry Juice May prevent urinary tract infection by interfering with bacterial adhesion in the urinary tract Daily consumption helps prevent UTIs in younger and older women; may not be e?ective in the 30-60 yo age group May interfere with warfarin Monitor INR Echinacea May have antiviral, anti-inﬂammatory, and immunostimulant e?ects E?ectiveness not known May interfere with immunosuppressant drugs Common Supplements Feverfew Migraine prophylaxis MOA not known increase the risk of bleeding in patients taking antiplatelet drugs (for example, aspirin) or anticoagulants (for example, warfarin or heparin) Great variability from product to product commercially Flaxseed Constipation and dyslipidemias; source of omega-3 fatty acids Provides soluble plant ﬁber and alpha-linolenic acid Decreases cholesterol (8-18%) but does not a?ect HDL, triglycerides Avoid defatted ﬂaxseed in patients with hypertriglyceridemia Take 1 hour before or 2 hours after medications Common Supplements Garlic Used to reduce levels of triglyceride (TG) and LDL and to raise HDL – this is speculative Used to lower blood pressure suppress platelet aggregation, increase arterial elasticity, and decrease formation of atherosclerotic plaque Bad breath Reduces levels of at least two drugs: cyclosporine (an immunosuppressant) and sasquinavir (a protease inhibitor used to treat HIV infection). 1 – 2 cloves per day to be e?ective Must be raw Common Supplements Ginger root Used to treat vertigo and to suppress nausea and vomiting associated with motion sickness, morning sickness, seasickness, chemotherapy, and general anesthesia Anti-inﬂammatory and analgesic properties that may help people with arthritis and other chronic inﬂammatory conditions Can suppress platelet aggregation Can lower blood sugar and therefore may potentiate the hypoglycemic eNects of insulin and other drugs for diabetes Ginkgo biloba Can increase pain-free walking distance in patients with peripheral arterial disease Generally well tolerated Interactions with antiplatelet and anticoagulant drugs → bleeding Common Supplements Glucosamine Used widely to treat osteoarthritis of the knee, hip, and wrist Use with caution in patients with shellﬁsh allergy Adverse e?ects: GI disturbances, such as nausea and heartburn Interactions with conventional drugs: May increase risk of bleeding Probiotics Used for Irritable bowel syndrome, ulcerative colitis, C. di^icile associated diarrhea Beneﬁcial bacteria and yeast Generally well tolerated, with some GI e?ects Flatulance (this could be a social issue) Resveratrol Antioxidant of plant origin (grape juice (→wine), cranberries, blueberries, peanuts) promoted for antiaging e?ects and for protection against chronic diseases Common Supplements Saw Palmetto Relieve urinary symptoms associated with benign prostatic hyperplasia (BPH) MOA is unknown Use is questionable; insu?icient evidence to support e?ectiveness DO NOT USE IN PREGNANCY Soy Possibly e?ective in treating menopausal symptoms Do not use with anti-estrogens May increase risk for oxalate kidney stones (Remember NUR 612) Common Supplements to AVOID Comfrey Topical use appears safe May result in veno-occlusive disease → liver damage Kava Can result in severe liver damage This is restricted in Germany, Canada, Switzerland, France, and Australia BUT NOT IN THE US (Do they know something that we don’t know?) Ma Huang (ephedra) Elevates blood pressure; stimulates the heart and CNS Associated with stroke, myocardial infarction and death Banned in the US (but does not apply to ephedra in traditional Asian meds not marketed as dietary supplements) St. John’s Wort Induces the cytochrome P450 system Accelerates metabolism of many prescription and OTC drugs Decreases eNectiveness of many prescription and OTC drugs NOTE All information needed for this chapter is found in the PowerPoint presentation. If information is needed for clariﬁcation or expansion, then use the text. Do not spend time learning doses (they can always be found in references) but do have an appreciation of the di?erences in adult and child dosing. The most recent protocols are from 2021 and are found at https://www.cdc.gov/std/treatment- guidelines/STI-Guidelines-2021.pdf (This is a 192-page document!) Current as of 30 October 2024) Objectives 1. List the common sexually transmitted infections and the organisms responsible for the infection 2. List the most common drugs used to treat each of the listed STIs 3. Explain the importance of obtaining a gonorrhea culture when treating adolescents for gonorrhea 4. Describe the most common signs and symptoms of the listed STIs 5. Describe the di?erent stages of syphilis 6. Of the common treatments used for STIs, list the drugs that should not be used with children or in pregnancy and explain why 7. Describe where the most current STI treatment protocols can be obtained Important Notice In all states, the diagnosis of sexually transmitted infection(s) in the prepubertal child requires immediate notiﬁcation of child protection services. https://www.cdc.gov/std/treatment-guidelines/table-8.htm Sexually Transmitted Infections (STIs) Formerly called sexually transmitted diseases Very common in the US Treatment changes often The text cites the CDC STD treatment guidelines from 2010. Most current CDC STD treatment guidelines are from 2021 Remember that partners should be treated as well as patient to prevent recurrence Cost of STIs Content source: Division of STD Prevention, National Center for HIV, Viral Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention Chlamydia The most common STI A?ects ~ 2.8 million people per year Screening recommended in all sexually active (SA) women < 25 and SA women > 25 with a new partner Can cause Genital tract infections Untreated may cause signiﬁcant pelvic infection (PID) and tubal damage resulting in ectopic pregnancy In newborn infants Ophthalmia Pneumonia Proctitis Conjunctivitis Lymphogranuloma venerum (LGV) Chlamydia Adults and Adolescents Urethral, cervical or rectal infections Azithromycin 1 gm oral dose x one or Doxycycline 100 mg PO BID x 7 days Pregnant women Azithromycin 1 gm oral dose x one or Amoxicillin 500 mg PO TID x 7 days Infants with pneumonia or ophthalmia Erythromycin ethyl succinate l2.5 mg/kg QID x 14 days Chlamydia Preadolescent children Always consider sexual abuse as cause of infection < 45 kg, erythromycin ethylsuccinate l2.5 mg/kg PO QID x 14 days > 45 kg AND < 8 yo, azithromycin single 1 gm dose PO > 8 yo, azithromycin single 1 gm dose PO or doxycycline 100 mg PO BID x 7 days (issue here is staining of teeth; avoid if possible Lymphogranuloma venereum More common in tropical countries Doxycycline 100 mg PO BID x 21 days Gonorrhea Caused by Neisseria gonorrhea (Gram-negative diplococci) ~ 700,000 new cases per year May be asymptomatic in women May cause serious damage to the reproductive tract. Men generally experience urethral burning with pus-like discharge Gonorrhea Urethral, cervical and rectal infection Single 500 mg IM dose ceftriaxone (Rocephin®) Mix with lidocaine for comfort If allergic, single 2 gram PO dose of azithromycin The advantage of ceftriaxone and azithromycin is chlamydia coverage Pharyngeal infection Single 500 mg IM dose ceftriaxone (Rocephin®) plus Single 1 gram PO dose of azithromycin Conjunctivitis Single 1 gram IM dose ceftriaxone (Rocephin®) Wash the eye with normal saline once Gonorrhea Disseminated Gonococcal Infection Caused by gonococcal bacteremia Petechial/pustular skin lesions Arthritis/arthralgia/tenosynovitis Meningitis Rare endocarditis In the absence of endocarditis or meningitis Ceftriaxone 1 gm IM or IV every 24 hours up to 2 weeks With endocarditis or meningitis Ceftriaxone 1 gm IM or IV every 12 hours up to 2 weeks Gonorrhea Preadolescent children Legal implications are great Diagnosis must be deﬁnitive Obtaining a culture is an absolute requirement before treatment Possible to obtain organisms through urine collection Treatment depends upon age and weight Localized infection < 45 kg, single 125 mg IM dose ceftriaxone > 45 kg, treat same as adults Neonatal infection Prophylaxis with 0.5% erythromycin ointment Neonatal ophthalmia can cause blindness if untreated Ceftriaxone 25 -50 mg/kg IM single dose not to exceed 250 mg Nongonococcal Urethritis (NGU) Very commonly seen as STI in younger population Commonly seen in college student health centers Caused by any organism OTHER than N. gonorrhoeae Chlamydia, Ureaplasma urealyticum, Trichomonas vaginalis, and Mycoplasma urealyticum are common causes Recommended treatments azithromycin 1 gm PO x one or doxycycline 100 mg PO BID x

NUR 613: Advanced Pharmacology and Therapeutics PDF

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