NUR 613 Advanced Pharmacology and Therapeutics Spring 2025 PDF

NUR 613: Advanced Pharmacology and Therapeutics: **MODULE 01: Virtual Classroom 01 SPRING 2025** page1image5101248 **Pharmacology: The Basics** **Drug** Any **chemical** that can affect living processes Pharmacology (*pharmakon-*poison; *ology-*study of) The study of drugs and their int...

NUR 613: Advanced Pharmacology and Therapeutics: **MODULE 01: Virtual Classroom 01 SPRING 2025** page1image5101248 **Pharmacology: The Basics** **Drug** Any **chemical** that can affect 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) **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 How does this happen? **STUDY, LEARN, and APPLY** Properties of an Ideal Drug: The Big 3 **Effectiveness** 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 effects** **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 **Terms Related to Adverse Drug Reactions** **Idiosyncratic effect** An uncommon drug response resulting from a genetic predisposition **Paradoxical effect** 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 **Effects of Drugs** (Kinetics and Dynamics) Drug-Drug Interaction **Addition (potentiation)** drugs of similar action-effect are **additive**: 1 + 1 = 2 (Diuretic + 𝛽-blocker) **Synergism** different drugs **enhance** the action of another drug: 1 + 1 = \> 2 (Bactrim→ two abxs combined) **Inhibition** the use of one drug **antagonizes** the effect of another drug: 1 + 1 \< 2 (Morphine + naloxone) Drug-Drug Interactions (KINETICS) Intensification of effects **Increased** therapeutic effects Sulbactam and ampicillin Increased adverse effects Aspirin and warfarin Reduction of effects **Inhibitory**: Interactions that result in reduced drug effects **Reduced therapeutic effects** Propranolol and albuterol **Factors That Determine the Intensity of Drug Responses** (Much more on this later!) How the drug is administered Pharmaco**kinetics** What the ***BODY DOES TO THE DRUG*** Pharmaco**dynamics** What the ***DRUG DOES TO THE BODY***\ Sources of Individual Variation Varies from ***PERSON TO PERSON*** **Factors that Determine the Intensity of Drug Responses** page12image4931792 **Stages of New Drug Development**  **Phase I:** The objective is to **evaluate drug metabolism, pharmacokinetics, and biologic effects**.\ **Phase II and III**: The objective is to **determine therapeutic effects, dosage range, safety, and effectiveness**. **Phase IV:** the new drug is released for general use, permitting observation of its **effects 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 (official 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 (nifed**ipine**, a calcium channel blocker) U.S. drugs and drugs outside the United States may have different active ingredients Products with the same generic name may have different active ingredients and different **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 --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 **Suffixes are helpful** (Do Not Learn Yet) **Therapeutic Use** **Pharmacologic Class** **Identifying Suffix** **Drug Name** ---------------------- ------------------------------------ ------------------------ ---------------------------------- Infection Penicillin antibiotic -cillin Amoxicillin Amoxil High cholesterol HMG-CoA reductase inhibitor -statin Simvastatin Zocor Peptic Ulcer Disease Proton pump inhibitor -prazole Omeprazole Prilosec Anticoagulation Low-molecular-weight heparin -parin Enoxaparin Lovenox Anxiety Benzodiazepines -epam -olam Diazepam Valium Alprasolam Xanax Erectile dysfunction Phosphodiesterase type 5 inhibitor -afil Sildenafil Viagra **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** +-----------------------+-----------------------+-----------------------+ | **Definitions for | **Abuse Potential** | | | Schedule I -- V | | | | Drugs** | | | +=======================+=======================+=======================+ | Schedule I\* | - High potential | page21image21029968 | | | for abuse | | | | | | | | - No currently | | | | accepted medical | | | | use in the United | | | | States | | | | | | | | - Lack of accepted | | | | safety for due of | | | | the drug under | | | | medical | | | | supervision | | +-----------------------+-----------------------+-----------------------+ | Schedule II | - High potential | | | | for abuse | | | | | | | | - Currently | | | | accepted medical | | | | use in the United | | | | States | | | | | | | | - Abuse may lead to | | | | severe | | | | psychological or | | | | physical | | | | dependence | | +-----------------------+-----------------------+-----------------------+ | Schedule III | - Potential for | | | | abuse less than | | | | schedule I and II | | | | drugs | | | | | | | | - Currently | | | | accepted medical | | | | use in the United | | | | States | | | | | | | | - Abuse may lead to | | | | moderate or low | | | | physical | | | | dependence or | | | | high | | | | psychological | | | | dependence | | +-----------------------+-----------------------+-----------------------+ | Schedule IV | - Lower potential | | | | for abuse than | | | | schedule III | | | | drugs | | | | | | | | - Currently | | | | accepted medical | | | | use in the United | | | | States | | | | | | | | - Abuse may lead to | | | | limited physical | | | | or psychological | | | | dependence | | | | relative to | | | | schedule III | | | | substances | | +-----------------------+-----------------------+-----------------------+ | Schedule V | - Low potential for | | | | abuse relative to | | | | schedule IV | | | | substances | | | | | | | | - Currently | | | | accept4ed medical | | | | use in the United | | | | States | | | | | | | | - 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* *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)* *Pharmaco**kinetics***: 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 different visual) page27image4870208 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 Diffusion **P-Glycoprotein** **P-glycoprotein**: Transmembrane protein that transports a wide variety of drugs ***out*** of cells **The 4 Basic Pharmacokinetic Processes** (A different visual) page30image4845344 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"** 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** **Factors affecting drug absorption\ **(Think of the pathophysiologic factors that affect 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 **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 Affecting 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 affects 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** 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 effect** 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 page46image5081328 **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 affected 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 effect\ 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 effectiveness **M**inimum **E**ffective **C**oncentration (**MEC**)\ the plasma drug level below which therapeutic effects will not occur **T**oxic **C**oncentration (**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 effective 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.)**   **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.) Time Course of Drug Responses (Kinetics): The Numbers page58image5077840 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 effect 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** Pharmaco***dynamics***: 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 effects 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 effects by helping the body use its preexisting capabilities** Types of Receptors (p. 48, Burchum & Rosenthal)  First and Second Messengers page67image5055424 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 affinity* of a drug to the** **receptor, the *higher the potency*** **The *lower the affinity* 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 efficacy is not always more desirable** Maximum Efficacy & Relative Potency **A Efficacy**, or maximal efficacy, is an index of the maximal response a drug can produce. The efficacy of a drug is indicated by the height of its dose-response curve. In this example, meperidine has greater efficacy than pentazocine**. Efficacy 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 sufficiently 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 effects 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 affinity and high intrinsic activity Example: Dobutamine mimics norepinephrine at cardiac receptors Agonists can make processes go "faster" or "slower" **depending upon the effect of the agonist on a particular cell** **Antagonists** Do not cause receptor activation but **cause pharmacologic effects by blocking the activation of receptors by agonists** **VERY IMPORTANT CONCEPT\ ** If no is agonist present, an antagonist will have no observable effect **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 affinity: Receptor occupied by whichever agent is present in the highest concentration **Noncompetitive vs. Competitive Antagonists** (**Figure 5.7,** Burchum & Rosenthal, p. 51, 12ed.) page78image5042992 **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 effective 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 effective 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 effect 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 effects\ Increased therapeutic effects Sulbactam and ampicillin\ Increased adverse effects Aspirin and warfarin Reduction of effects Inhibitory: Interactions that result in reduced drug effects Reduced therapeutic effects Propranolol and albuterol Reduced adverse effects 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 affect 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 effect 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 effects (for example, life-threatening dysrhythmias, suicidality, major fetal harm) - Ways to prevent or reduce harm (for example, avoiding a teratogenic drug during pregnancy) page93image5093600 Example of a black box warning **Pediatric Patients** Children **ARE NOT** little adults ▪Ongoing growth and development ▪Different age groups have different challenges\ ▪ Two-thirds (66%)of drugs used in pediatrics have never been tested in pediatric patients\ ▪Twenty percent (25%) of drugs were ineffective for children even though they were effective for adults\ ▪Thirty percent (30%) of drugs caused unanticipated side effects, 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 Endogenous compounds compete with drugs for available binding sites Blood-brain barrier capable of producing CNS toxicity as a side effect **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 effective 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 difference:\ ** 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 effects related to organ immaturity and ongoing growth and development Age-related effects:\ 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 differently to drugs and state how those differences could (or likely will) affect 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 effects 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 effect) 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!) ----------------------------------------------------------------------------------------------------------------------------------------------- **ABSORPTION of Drugs** **Increased Gastric pH\ Decreased absorptive surface area Decreased splanchnic blood flow Decreased GI motility\ Delayed gastric emptying** --------------------------- ------------------------------------------------------------------------------------------------------------------- **DISTRIBUTION of Drugs** **Increased body fat\ Decreased lean body mass (LBM) Decreased total body water Decreased serum albumin Decreased cardiac output (CO)** **METABOLISM of Drugs** **Decreased hepatic blood flow Decreased hepatic mass\ Decreased activity of hepatic enzymes** **EXCRETION of Drugs** **Decreased renal blood flow\ Decreased glomerular filtration rate (GFR) Decreased tubular secretion\ 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 effects in older adults Warfarin and certain central nervous system depressants Beta blockers **less effective** in older adults, even in the same concentrations Reduction in number of beta receptors\ Reduction in the affinity 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 difficult 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 affect 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 effects **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 Why is the concept of peak and trough important? (Think about your clinical experience.) **MEMORY TRICK**→ **Time Course of Drug Responses (Kinetics)**  page5image11855264 **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 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) Susceptible organisms (see Table 88-1, p. 1085-6 Burchum & Rosenthal) 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** **Bacterio*static* drugs can slow bacterial growth but *do not cause bacterial death*** **Bacteri*cidal* drugs are directly lethal to bacteria** **Animal *vs* Bacterial Cell** Note the differences: 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 difficulty 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 **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)??? Previous drug reactions Genetic factors **Dosage Size and Duration** The antimicrobial agent must be present: At the site of infection (**Kinetics**→ **Distribution**) For a sufficient length of time (**Kinetics**→ **Metabolism and Excretion**) Patient education is important Antibiotics must not be discontinued prematurely\ What might be the effect(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 shedding: extensive dental work may be an example Neutropenia Other indications **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 12^th^ 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 different 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 effect: Allergy All of the PCNs contain a **beta-lactam** ring 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 affinity for the penicillins Remember what was said earlier about receptors and affinity 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 page31image29230096 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: difficult to penetrate **Classification of Penicillins** Narrow-spectrum\ Penicillinase sensitive: peni**cillin** G, peni**cillin** V Narrow-spectrum\ Penicillinase resistant: naf**cillin**, oxa**cillin**, dicloxa**cillin** Broad-spectrum\ Aminopenicillins: ampi**cillin**, amoxi**cillin** Extended-spectrum Antipseudomonal: ticar**cillin**, pipera**cillin** 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 ineffective 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 effect of both drugs Probenecid\ Delays renal excretion of PCNs by competing with excretion transport in kidney Use with caution in renal disease\ PCN and bacterio**STATIC** 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 effects Rash Diarrhea Antipseudomonal PCNs Ticarcillin, piperacillin Effective 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) 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 Metabolism Minimal Excretion **Active** tubular excretion (**90%**); glomerular filtration (10%) 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. difficile* infection and *Adverse Effects* (vancomycin) in Burchum and Rosenthal Read: Key Points, and Summary of Major Nursing Implications\ Understand the differences 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 different therapeutic spectra of the different generation cephalosporins. 6. Explain distribution of the of the different 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 effect: 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) page45image28411728 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) **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 Difference Between Cephalosporin Generations**  Table 90.1, p. 1108, Burchum & Rosenthal, 12th ed. **Cephalosporins: Therapeutic Uses** (When learning, generalize and then know the exceptions) **First** generation\ Gram-positives: Effective 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 effective in the CSF **Third** generation\ Increased resistance to beta-lactamase **Increased activity** against Gram-negatives Ceftazidime has activity against *P. aeruginosa* Clinically effective 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 effective 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 Effects** **Allergies** Rash most common; develops 2 -- 5 days after exposure Severe reactions are uncommon 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 effect 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 different lines.** **Carbapenems** They all end in **penem** Beta-lactam (you should now know how they work) Very broad spectrum **EXCEPT MRSA** **Carbapenems** **Imipenem** Highly active against Useful for mixed infections **Excreted by KIDNEY** **Imipenem: Other Information** Adverse effects\ 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. difficile* 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. diff*)\ **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** **Oto**toxicity\ 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 differences 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 effusion. 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** **Externa**l 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   **Acute Otitis Media (AOM)** Inflammation of the middle ear Characteristics Fluid in the middle ear Otalgia -- children may tug on affected ear Etiology Bacterial Viral\ Usually begins as viral infection in the nasopharynx Diagnosis -- **must have all three** Acute onset Middle-ear effusion Middle-ear inflammation **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 months Antibacterial therapy Antibacterial therapy 6 months to 2 years Antibacterial therapy Antibacterial therapy if illness is severe; observation if illness is not severe\* 2 years and older Antibacterial therapy if illness is severe; observation if illness is not severe\* Observation, regardless of symptom 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 | **Recommend | | | | | Group and | ed | | | | | Illness | Drugs (See | | | | | Severity** | the SANFORD | | | | | | GUIDE)** | | | +-------------+-------------+-------------+-------------+-------------+ | | | **For Most | **For | | | | | Patients** | Patients | | | | | | with | | | | | | Penicillin | | | | | | Allergy | | | | | | (note the | | | | | | type of | | | | | | allergy)** | | +-------------+-------------+-------------+-------------+-------------+ | | **Patients | | | | | | Receiving | | | | | | Immediate | | | | | | Antibiotic | | | | | | Therapy** | | | | +-------------+-------------+-------------+-------------+-------------+ | | **Non-sever | **Amoxicill | ***Non--typ | | | | e | in, | e | | | | illness** | 40--45 | I | | | | | mg/kg twice | allergy:*** | | | | | daily** | | | | | | | **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** | | | | | | | | | | | | ***Type I | | | | | | allergy | | | | | | (anaphylaxi | | | | | | s):*** | | | | | | | | | | | | **Azithromy | | | | | | cin, | | | | | | 10 mg/kg on | | | | | | day 1, | | | | | | then\ | | | | | | 5 mg/kg on | | | | | | days 2, 3, | | | | | | 4, and 5 | | | | | | *or*** | | | | | | | | | | | | **Clarithro | | | | | | mycin, | | | | | | 7.5 mg/kg | | | | | | twice | | | | | | daily** | | | | | | | | | | | | **Clindamyc | | | | | | in,** | | | | | | 20 to 30 | | | | | | mg/kg/day | | | | | | in 3 doses | | +-------------+-------------+-------------+-------------+-------------+ | | **Severe | **Amoxicill | **Ceftriaxo | | | | illness** | in, | ne, | | | | | 45 mg/kg | 50 mg/kg IM | | | | | twice\ | for 1 or 3 | | | | | daily | days (if | | | | | *plus* | non-Type I | | | | | 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) | | | | | | ** | | | | +-------------+-------------+-------------+-------------+-------------+ | | **Non-sever | **Amoxicill | ***Non--typ | | | | e | in, | e | | | | illness** | 45 mg/kg | I | | | | | twice\ | allergy:*** | | | | | daily | | | | | | *plus* | **Ceftriaxo | | | | | clavulanate | ne, | | | | | , | 50 mg/kg IM | | | | | 3.2 mg/kg | or IV for 3 | | | | | twice | days** | | | | | daily** | | | | | | | ***Type I | | | | | | allergy | | | | | | (anaphylaxi | | | | | | s):*** | | | | | | | | | | | | **Clindamyc | | | | | | in, | | | | | | 30--40 | | | | | | mg/kg/day | | | | | | in 3 | | | | | | divided | | | | | | doses** | | +-------------+-------------+-------------+-------------+-------------+ | | **Severe | **Ceftriaxo | **Clindamyc | | | | illness** | ne, | in | | | | | 50 mg/kg IM | (plus a | | | | | for 3 | third-gener | | | | | days** | ation | | | | | | cephalospor | | | | | | in | | | | | | if | | | | | | non--type I | | | | | | penicillin | | | | | | allergy), | | | | | | tympanocent | | | | | | esis** | | +-------------+-------------+-------------+-------------+-------------+   **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 Effusion (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 effect ‒ do not use**  **Serous effusion** **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** **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 effective 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 effects 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 effectiveness (toxicity) or decreased effectiveness **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 effects -- 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 effects *before* I take it, or one that is evaluated for adverse effects only *after* it caused me harm?" **Herbal Product Standardization** There is often uncertainty about the amounts of active ingredients - multifactorial Standardization is difficult 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 effective as estrogen; long-term use not evaluated May **potentiate antihypertensives** **Coenzyme Q-10 (CoQ-10)** Potent antioxidant \*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 effective in the 30-60 yo age group **May interfere with warfarin** Monitor INR **Echinacea** May have antiviral, anti-inflammatory, and immunostimulant effects Effectiveness 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 affect 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 effective\ 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 effects 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 effects: 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. difficile* associated diarrhea Beneficial bacteria and yeast\ Generally well tolerated, with some GI effects **Flatulance** (this could be a social issue) **Resveratrol\ ** Antioxidant of plant origin (grape juice (→wine), cranberries, blueberries, peanuts) promoted for antiaging effects 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; insufficient evidence to support effectiveness **DO NOT USE IN PREGNANCY** **Soy\ ** Possibly effective 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 effectiveness 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 differences in adult and child dosing. The most recent protocols are from 2021 and are found at (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 different 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 a