NR566 Midterm Study Guide updated and comprehensive, Study notes of Nursing

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NR566 Midterm Study Guide

updated and comprehensive

Advanced Pharmacology For Care

Of The Family (2024-2025)

Guide Be familiar with the interactive activities throughout course modules. You could see variations of those same questions on your exams.

Week 1

Class Reading

• Antibacterial Treatments: o The primary goal of antibiotic therapy is to kill bacteria without harming host tissues o Four factors to consider: ▪ Host: - Consist primarily of the immune system and phagocytic cells (macrophages and neutrophils) - Allergy: history of allergy, cross-allergy, or intolerance - Preexisting conditions: HIV, cancer, autoimmune disorders, diabetes - Renal/hepatic function: doses may need to be reduced. Consider creatinine clearance. - Age: dose adjustments may be required for pediatric and geriatric patients- weight-based may be appropriate. - Pregnancy and lactation: Be aware of teratogenic effects of certain classes of medications - Recent antibiotic use: Be aware of possible drug-resistant bacteria - Exposure history: travel, congregate care settings, close contacts ▪ Syndrome: - What system is impacted? - How aggressive is the infection? - Consider non-bacterial causes of symptoms (i.e. viral, fungal, or non- infections) ▪ Pathogen: - Consider the pathogens that may be causing the illness - Cultures are the most accurate way to identify pathogens - Susceptibility: o Antimicrobial Susceptibility Testing (AST) ▪ Lab test to determine how pathogen grows while exposed to specific drugs (in a petri dish) ▪ Results are reported as: - Susceptible - Resistant - Intermediate - Drugs: o When choosing an antibiotic, three principal factors must be considered: ▪ The identity of the infecting organism ▪ Drug sensitivity of the infecting organism

Guide

• Antibiotic Stewardship o Overuse occurs when providers: ▪ Fail to perform susceptibility testing ▪ Overprescribe antibiotics for very young and very old patients or patients with multiple medical comorbidities ▪ Succumb to pressure to prescrive o

Guide o CDC Campaign to combat antimicrobial resistance: ▪ Focus Area I: Surveillance, Prevention, and Control of Antimicrobial Resistant Infections. Goals include improving the detection, monitoring, and characterization of drug-resistant infections in humans and animals, as well as improving the definition, characterization, and measurement of the impact of antimicrobial drug use. ▪ Focus Area II: Research. Goals include facilitation of basic research on antimicrobial resistance, as well as translation of basic research into practice. Support for epidemiologic studies to identify key drivers of the emergence and spread of antimicrobial resistance is of great importance. ▪ Focus Area III: Regulatory Pathways for New Products. Aims for product development include provision of information on the status of antibacterial drug product development and encouraging development of rapid diagnostic tests and vaccines. ▪ Focus Area IV: Product Development. Goals include providing a systematic assessment of current and future needs for antimicrobial resistance products and promoting the development of drugs targeted to address areas where unmet needs exist.

• Selective Toxicity o Disruption of the Bacterial Cell Wall ▪ Bacterial are encased in a rigid cell wall  several families of drugs (penicillins and cephalosporins) weaken the cell wall and promote bacterial lysis o Inhibition of an Enzyme Unique to Bacteria ▪ Sulfonamides represent antibiotics that are selectively toxic because they inhibit an enzyme critical to bacterial survival but not to our survival o Disruption of Bacterial Protein Synthesis ▪ Antibiotics that impair protein synthesis in bacterial while leaving mammalian protein synthesis untouched o Classification of Antimicrobial Drugs by Mechanism of Action

Guide o Conjugation ▪ Conjugation is a process by which extrachromosomal DNA is transferred from one bacterium to another. To transfer resistance by conjugation, the donor organism must possess two unique DNA segments, one that codes for the mechanisms of drug resistance and one that codes for the “sexual” apparatus required for DNA transfer. Together, these two DNA segments constitute an R factor (resistance factor).

• How Do Antibiotics Promote Resistance? o If a drug-resistant organism is present, antibiotics will create selection pressure favoring its growth by killing off sensitive organisms. In doing so, the drug will eliminate the toxins they produce and will, hence, facilitate survival of the microbe that is drug resistant o All antimicrobial drugs promote the emergence of drug-resistant organisms
• Superinfection: o A new infection that appears during the course of treatment for a primary infection o New infections develop when antibiotics eliminate the inhibitory influence of normal flora, thereby allowing a second infectious agent to flourish. A common example of superinfection is the development of a vaginal Candida infection in a female treated with a broad spectrum antibiotic for a urinary tract infection. Study Guide
• Community Acquired Pneumonia (CAP) o Pneumonia is commonly seen condition and a leading cause of death in the United States o Common pathogens ▪ General population
• Streptococcus pneumonia (gram-positive)
• Atypical bacteria (Mycoplasma pneumoniae)
• Viruses (e.g., influenza, respiratory syncytial virus) ▪ Smokers and those with COPD
• Haemophilus influenzae (gram-negative) ▪ Those with cystic fibrosis (CF)
• Pseudomonas aeruginosa (gram negative) o First line treatment for previously healthy adults ▪ Macrolides, Doxycyline, Amoxicillin ▪ What to give if first drug didn’t work
• Respiratory Fluoroquinolone if not received abx in the past 3 months o Treatment for M. Pneumoniae in pediatric patient (Specific/example antibiotic from drug class will be provided) ▪ Macrolides (Erythromyin) and tetracyclines o Treatment of CAP in pregnancy ▪ Amoxicillin, cephalosporins, or Erythromycin o If someone has been treated with an antibiotic in the previous 90 days of contracting CAP, a quinolone would be a prudent choice to prescribe. ▪ Be familiar with drug examples within the antibiotic classes.

Guide

• Treatment of chlamydial pneumonia in infant (options will include dose, but if you know the correct drug, the dose will come with it on the exam so no need to memorize dose) o Macrolide (Azithromycin): 500mg orally on day 1 followed by 250 mg once daily on days 2-
• Atypical Pneumonia o These patients are less likely to have a fever and usually present with complaints of fatigue accompanied by a cough that interferes with sleep. This form of atypical pneumonia is often thought to be a cold and managed symptomatically with over-the-counter medications unless medical care is sought. It is commonly referred to as 'walking pneumonia'. Treatment is similar to CAP. o If a patient has failed therapy with a macrolide or doxycycline, one must consider why the patient failed. The most common reasons are either medication adherence issues or the presence of resistant organisms. If a resistant organism is suspected, then the use of one of the respiratory fluoroquinolones active against S. pneumoniae is warranted
• Broad vs narrow spectrum agents o When to use which one ▪ Broad-spectrum: - Targets wider number of bacteria types. - Acts on both gram- and gram + organisms. - Commonly used for empiric therapy when the pathogen is unknown or infection with multiple types of bacteria is suspected. - Risks include disruption of normal flora and development of antibiotic resistance. - Give before receiving culture results - More likely to facilitate emergence of drug-resistant organisms and superinfections ▪ Narrow-spectrum:
• Effective against a specific bacteria type.
• Used when infecting pathogen is known.
• Reduces risk disruption of normal flora and development of antibiotic resistance.
• Preferred when possible.
• Empiric antibiotics o What are they ▪ When waiting for culture results, it may be necessary to start treatment with broad-spectrum antibiotics to address the infection and prevent it from spreading. This initial treatment approach is known as empiric therapy and is often used in situations where waiting for culture results could lead to further complications. Once culture results are available, treatment can be adjusted accordingly to ensure that the patient receives the most effective treatment possible. ▪ If necessary, a broad-spectrum agent can be used for initial treatment. After the identity and drug sensitivity of the infecting organism have been determined, we can switch to a more selective antibiotic. When conditions demand that we start therapy in the absence of laboratory data, it is essential that samples of exudates and body

Guide before initiation of treatment; if antibiotics are present at the time of sampling, they can suppress microbial growth in culture and can thereby confound identification. o When to prescribe ▪ Empiric therapy is initiated based on the NP's knowledge of the patient's history, typical pathogens, gram stain results, and local susceptibility reports on which antibiotics work best in certain geographic locations. ▪ Critically ill patients receive immediate empiric antibiotics after the first set of cultures obtained; do not wait for results. ▪ Empiric (broad-spectrum) given for hospitalized patients until culture results are available ▪ Subacute illnesses may benefit from waiting until multiple sets of cultures are obtained over a timeframe to ensure appropriate diagnosis. ▪ Ambulatory patients may be treated based on clinical presentation alone. ▪ Combination therapy with multiple drug classes may be given to increase the pathogen coverage ▪ Once microbiology results are available, change the prescription to narrow therapy for pathogen susceptibility ▪

• Clostridium difficile associated diarrhea o How to treat ▪ Vancomycin ▪ Metronidazole

Guide ▪ o Drug class known for ALL drugs in class to promote development of C. Diff. ▪ Antibiotics o Drug classes of antibiotics resistant to C-diff ▪ Aminoglycosides or cephalosporins

• Drugs that Weaken the Bacterial Cell Wall: Penicillin, Cephalosporins
• Penicillin o Penicillins may be prescribed for common infections in primary and acute care settings. They are bactericidal. There are four classes of penicillin, based on antimicrobial spectrum: ▪ Narrow-spectrum- penicillinase sensitive: Penicillin G, Penicillin V ▪ Narrow-spectrum- penicillinase resistant: Nafcillin, Oxacillin, Dicloxacillin ▪ Broad spectrum: Ampicillin, Amoxicillin ▪ Extended spectrum: Piperacillin ▪ Penicillin/Beta-Lactamase combinations: Ampicillin/sulbactam (Unasyn), Amoxicillin/clavulanate (Augmentin), Piperacillin/tazobactam (Zosyn) o Cross-sensitivity reactions with which drug classes ▪ Penicillins Combined with a Beta-Lactamase Inhibitor - Ampicillin/ sulbactam (Unasyn) - Amoxicillin/ clavulanate (Augmentin and Clavulin) - Piperacillin/ tazobactam (Zosyn and Tazocin)

Guide ▪ Amoxicillin first line for acute otitis media and sinusitis ▪ Penicillin used for streptococcal pharyngitis ▪ Amoxicillin/clavulanate first line for infection following animal or human bites o Rational Drug Selection ▪ Defining tests (rapid strep) vs. empiric method ▪ Cost o Baseline Data ▪ Culture & Sensitivity o Monitoring ▪ Allergy symptoms ▪ C.diff diarrhea ▪ Renal function in prolonged therapy o Contraindications ▪ History of severe allergic reactions

• PCNs
• Cephalosporins
• Carbapenems o Patient Education ▪ Educate patient on antibiotic resistance and why it is important to not overuse antibiotics ▪ Signs and symptoms to look for to report to their provider ▪ Either not responding to treatment ▪ Experiencing ADRs ▪ Importance of completing the full course of antibiotics o Life Span: ▪ Infants
• Safe: Syphilis, Meningitis, Group A Strep ▪ Children/ adolescents:
• Commonly used ▪ Prescribing in pregnant patients
• Most are pregnancy category B
• No 2 nd^ and 3 rd^ trimethoprimester fetal risk ▪ Lactation
• Amoxicillin is safe ▪ Older adults:
• Renal dose adjustments
• Cephalosporins o Cephalosporins are structurally and chemically related to penicillins and are bactericidal with a low toxicity. They are divided into 5 generations based on their order of development and spectrum of antibiotic activity. ▪ 1st generation: Cephalexin (Keflex) ▪ 2nd generation: cefoxitin (Mefoxin) ▪ 3rd generation: cefotaxime (Claforan) ▪ 4th generation: cefepime (Maxipime) ▪ 5th generation: ceftaroline (Teflaro)

Guide o Susceptible Pathogens ▪ 1st generation: gram positive staphylococci and streptococci ▪ 2nd -5th generations: broad spectrum gram positive and gram negative bacteria o o Pharmacodynamics ▪ Cephalosporins are derivatives of 7-aminocephalosporanic acid containing the beta-lactam ring which is structurally and chemically similar to PCNs. Cephalosporins Inhibit mucopeptide synthesis in the bacterial cell wall ▪ Four generations of Cephalosporins based on when they were introduced into clinical practice.

• First-generation (Duricef, Keflex) o Used for skin and soft tissue infections o Primarily active against gram-positive bacteria, S. aureus and S. epidermidis
• Second generation (Ceftin, Ceclor, Cefzil) o Active against same as first-generation, plus Klebsiella, Proteus, E. coli (Gr+ & Gr-)
• Third generation (Cedax, Suprax, Rocephin, Omnicef, Spectracef, Vantin) o Used for broader indications (Gr+, Gr-, and Beta- lactamase) o More active against gram-negative bacteria
• Fourth generation (Cefepime)

Guide o Life Span Considerations ▪ Infants

• 3 rd^ generation ok ▪ Children/adolescents
• Cephalosporins commonly used o Otitis media o Gonococcal o Pneumococcal ▪ Prescribing in pregnant patients
• Telavancin- o BBW
• Cephalosporins o Safe ▪ Lactation
• Cephalosporins safe ▪ Older adults
• Dose adjustments for renal function
• Carbapenems o MOA ▪ Binds to PBP1 & PBP
• Cell lysis o Baseline Data ▪ C&S o Monitoring ▪ None suggested o Contraindications ▪ Valproate o Adverse Effects ▪ Dose adjustment for renal impairment o Therapeutic Goal: Treatment of infections caused by susceptible organisms. o Baseline Data: Take samples for culture to determine the identity and sensitivity of the infecting organism. o Monitoring: No routine laboratory monitoring is suggested. o Identifying High-Risk Patients: Patients using valproate to control seizures should not be placed on imipenem. o Evaluating Therapeutic Effects: Monitor for indications of antimicrobial effects, including reduction in fever, pain, edema, and inflammation. o Minimizing Adverse Effects: Dosage should be reduced in patients with renal impairment
• Vancomycin o MOA ▪ Does not interact with PBPs ▪ Binds molecules for cell wall biosynthesis o Indication ▪ C. Diff ▪ MRSA

Guide ▪ Allergy to PCN o Baseline Data ▪ C&S o Monitoring ▪ Drug levels o Caution ▪ Renal impairment o Therapeutic Goal: Treatment of serious infections, including C. diff. infection, infection with methicillin-resistant S. aureus, and serious infections caused by susceptible organisms in patients allergic to penicillin. o Baseline Data: Take samples for culture to determine the identity and sensitivity of the infecting organism. o Monitoring: Vancomycin drug levels should be monitored during IV administration. o Identifying High-Risk Patients: Use with caution in patients with renal impairment. o Evaluating Therapeutic Effects: Monitor for indications of antimicrobial effects, including reduction in fever, pain, edema, and inflammation.

• Telavancin o Telavancin (Vibativ) is the first representative of a new class of agents, the lipoglycoproteins, synthetic derivatives of vancomycin. Like vancomycin, telavancin is active only against gram-positive bacteria. Cell kill results from two mechanisms. ▪ First, similar to vancomycin, telavancin inhibits bacterial cell wall synthesis. ▪ Second, telavancin binds to the bacterial cell membrane and, thus, disrupts membrane function. o Telavancin is approved only for IV therapy of complicated skin and skin structure infections caused by susceptible strains of the following gram- positive organisms: S. aureus (including methicillin-sensitive and methicillin-resistant strains), Streptococcus pyogenes, Streptococcus agalactiae, Streptococcus anginosus group, and Enterococcus fecalis (but only vancomycin-sensitive strains). o BBW: Telavancin, when used to treat hospital-acquired or ventilator- associated bacterial pneumonia in patients with a creatinine clearance of less than 50 mL/min, has been associated with increased mortality compared with vancomycin.
• Bacteriostatic Inhibitors of Protein Synthesis: Tetracyclines (Tetracycline), Macrolides (Erythromycin), Oxazolidinone (Linezolid), Glycylcycline (Tigecycline), Other (Clindamycin)
• Tetracyclines o Tetracycline, doxycycline o MOA ▪ Inhibit binding of transfer RNA to messenger RNA o Susceptible Pathogens ▪ Tetracyclines: Broad spectrum gram + and gram -, Rikettsia, H. pylori, Borrelia burgdorferi, Bacillus anthracis, Vibrio cholerae o Clinical Use:

Guide

• Macrolide s ▪ Lactation - Should be avoided ▪ Older Adults - Several drug interactions o Digoxin o Erythromycin, azithromycin (Zithromax), clarithromycin (Biaxin) o Susceptible Pathogens ▪ Macrolides- Erythromycin: Bordetella pertussis, Corynebacterium diptheriae ▪ Azithromycin and clarithromycin: Gr + and Gr -, atypical infections o Clinical Use ▪ Whooping cough, diptheria, respiratory tract o Patient education needed ▪ Administer with meals o Erythromycin ▪ MOA
• Blocks addition of new amino acids ▪ Caution
• QT prolongation o Risk for torsades de pointes
• CYP3A4 = 5x increased risk for sudden cardiac death
• CYP3A4 Inhibitos o CCB o Azole antifungal drugs o HIV protease inhibitors o Nefazodone
• Risk of toxicity o Theophylline o Carbamazepine o Warfarin
• Antagonist o Chloramphenicol o Clindamycin ▪ Adverse Effects
• GI upset o Administer with meals
• Lincosamides: Clindamycin o Not a macrolide o BBW: Can promote severe C-Diff o Limited indications o MOA ▪ Clindamycin binds to the 50S subunit of bacterial ribosomes and thereby inhibits protein synthesis. The site at which clindamycin binds overlaps the binding sites for erythromycin and chloramphenicol. As a result, these

Guide agents may antagonize each other's effects. Accordingly, there are no indications for concurrent use of clindamycin with these other antibiotics. o Clinical Use ▪ Because of its efficacy against gram-positive cocci, clindamycin has been used widely as an alternative to penicillin. The drug is employed primarily for anaerobic infections outside the CNS (it does not cross the blood– brain barrier). Clindamycin is the drug of choice for severe group A streptococcal infection and for gas gangrene (an infection caused by C. perfringens), owing to its ability to rapidly suppress synthesis of bacterial toxins

• Aminoglycosides o Narrow spectrum antibiotics used primarily against aerobic gram-negative bacilli o MOA ▪ Inhibit protein synthesis ▪ Premature termination of protein synthesis ▪ Produce abnormal proteins o Therapeutic Use ▪ Parenteral - Gentamicin - Tobramycin - Amikacin ▪ Topical - Gentamicin & Tobramycin o Eye infections - Neomycin o Ear and Eye o Baseline Data ▪ Blood cultures ▪ Urine cultures o Monitoring ▪ Peaks & troughs ▪ Renal function o Contraindications & Side effects ▪ Caution - Renal impairment - Hearing impairment - Other ototoxic or nephrotoxic drugs o BBW: ▪ Ototoxicity ▪ Neurotoxicity - Numbness - Tingling - Muscle twitching - Seizures ▪ Nephrotoxicity ▪ Neuromuscular blockade