NR 566 Midterm Exam Study Guide/NR566 Midterm Study Guide(V1)(New,2023/2024):Chamberlain, Study Guides, Projects, Research of Nursing

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NR 566 Midterm Exam Study Guide Week 1 -Things to know about each of the major antibiotic drug classes Bactericidal vs. Bacteriostatic • Bactericidal antibiotics directly kill bacteria o preferred for immunocompromised patients such as those with diabetes, HIV, or cancer & for those who have overwhelming infections. o Agents : aminoglycosides, beta-lactams, fluoroquinolones, metronidazole, most antimycobacterial agents, streptogramins, & vancomycin. • Bacteriostatic agents inhibit bacterial proliferation while the host's immune system does the killing. o Agents : clindamycin, macrolides, sulfonamides, & tetracyclines o Bactericidal agents: “BANG Q R.I.P” - Beta-lactams, Aminoglicosides, Nitroimidazoles (Metronidazole), Glycopeptides (Vancomycin), Quinolones, Rifampicin, Polymyxins (Colistin) o Bacteriostatic agents : “Ms. Colt” - Macrolides, Sulfonamides, Chloramphenicol, Oxazolidinones, Lincosamides (Clindamycin), Tetracyclines *Bactericidal antibiotics kill bacteria directly, & bacteriostatic antibiotics stop/weaken bacteria from growing to enable the immune system to take hold of infection* Aminoglycosides (narrow-spectrum antibiotics used primarily against aerobic gram-negative bacilli; disrupt protein synthesis by binding to the 30S ribosomal subunit, resulting in rapid bacterial death) (p. 683) • Examples : Gentamicin, Tobramycin, Amikacin, Neomycin, Kanamycin, Streptomycin, Paromycin, Plazomicin (p. 687) • Indications for use : Treatment of serious infections caused by gram-negative aerobic bacilli (Pseudomonas aeruginosa, enterobacteriaceae, topical infection, ocular bacterial infections, intestinal amebiasis, complicated UTI) (p. 687) • Contraindications & high-risk patients : Aminoglycosides should be used with caution in patients with renal impairment, preexisting hearing impairment, & those receiving ototoxic & nephrotoxic drugs. (pp. 685-687) • Monitoring needs : Aminoglycoside levels (peaks & troughs) & renal function must be monitored. Monitor for neurotoxicity, ototoxicity, & nephrotoxicity. • Which ones require renal dosing adjustments and how much (i.e., 25%, 50%, etc.) : To avoid serious toxicity, we must reduce dosage size or increase the dosing interval in patients with kidney disease. (p. 685) *Clarithromycin • Patient education : *Patients should be informed about the symptoms of vestibular & cochlear damage & instructed to report them. • Lifespan considerations : (p. 685) Infants: Aminoglycosides are approved to treat bacterial infections in infants younger than 8 days. Dosing is based on weight & length of gestation. Children/adolescents: Aminoglycosides are safe for use against bacterial infections in children & adolescents. Pregnant women: There is evidence that use of aminoglycosides in pregnancy can harm the fetus. Breastfeeding women: Gentamicin is probably safe to use during lactation. There is limited information regarding its use in this way. Older adults: Caution must be used regarding decreased renal function in the older adult. Cephalosporins (Beta-lactam antibiotics similar in structure & actions to the penicillins; bactericidal; often resistant to beta-lactamases, & active against a broad spectrum of pathogens; most widely used group of antibiotics) (p. 669) • Examples : 1st generation: Cephalexin (Keflex); 2nd generation: Cefoxitin, Cefaclor (Ceclor); 3rd generation: Cefotaxime, Cefdinir, Ceftriaxone (Rocephin); 4th generation: Cefepime, 5th generation: Ceftaroline • Indications for use : 1st generation: Staphylococci or streptococci (Use in patients with mild PCN allergy, strep pharyngitis, skin infections, & surgical prophylaxis) 2nd generation: Haemophilus influenzae, Klebsiella, pneumococci, & staphylococci (Otitis, sinusitis, & respiratory tract infections) 3rd generation: Pseudomonas aeruginosa, Neisseria gonorrhoeae, & Klebsiella, Serratia (Meningitis, gram- negative nosocomial infections) 4th generation: Pseudomonas aeruginosa (Hospital-acquired pneumonia & complicated intra-abdominal & UTIs due to resistant pseudomonas) 5th generation: Methicillin-resistant Staphylococcus aureus (MRSA-associated infections). (p. 671) • Contraindications & high-risk patients : Cephalosporins are contraindicated for patients with a history of allergic reactions to cephalosporins or severe reactions to penicillin. Patients using cefazolin & cefotetan must not consume alcohol. Use cefotetan, cefazolin, & ceftriaxone cautiously in patients taking other agents that also promote bleeding (anticoagulants, thrombolytics, NSAIDS, etc). (pp. 670-671) • Monitoring needs : Monitor for signs of C. dif infection & renal function in patients with renal impairment and/or prolonged use. • Which ones require renal dosing adjustments and how much (i.e., 25%, 50%, etc.) : In patients with renal insufficiency, dosages of most cephalosporins must be reduced to prevent accumulation to toxic levels. (EXCEPTION: Ceftriaxone (3rd generation) is eliminated largely by the liver, so dosage reduction is unnecessary in patients with renal impairment) (p. 669) • Patient education : *All cephalosporins can promote C. dif infection, so patients should be instructed to report an increase in stool frequency. • Lifespan considerations : Infants: 3rd generation cephalosporins are used to treat bacterial infections in neonates as well as infants. Children/adolescents: Cephalosporins are commonly used to treat bacterial infections in children, including otitis media & gonococcal & pneumococcal infections. Pregnant women: All cephalosporins appear safe for use in pregnancy. Breastfeeding women: Cephalosporins are generally not expected to cause adverse effects in breastfed infants. Older adults: Doses should be adjusted in older adults with decreased renal function. Tetracyclines (broad-spectrum antibiotics active against a wide variety of gram-positive & gram-negative bacteria; suppress bacterial growth by binding to the 30S ribosomal subunit & inhibiting protein synthesis, extensive use • Which ones require renal dosing adjustments and how much (i.e., 25%, 50%, etc.) : *Amoxicillin, Augmentin, Penicillin • Patient education : • Lifespan considerations : (p. 666) Infants: Penicillins are used safely in infants with bacterial infections, including syphilis, meningitis, & group A streptococcus. Children/adolescents: Penicillins are a common drug used to treat bacterial infections in children. Pregnant women: Although there are no well-controlled studies in pregnant women, evidence we do have suggests there is no 2nd or 3rd trimester fetal risk. Breastfeeding women: Amoxicillin is safe for use in breastfeeding mothers. Data are lacking regarding transmission of some other penicillins from mother to infant through breast milk. Older adults: Doses should be adjusted in older adults with renal dysfunction. Sulfonamides (usually bacteriostatic; suppress bacterial growth by inhibiting the synthesis of tetrahydrofolate, a folate derivative; broad-spectrum antimicrobials) (p. 689) • Examples : Sulfadiazine, Sulfamethoxazole, Sulfacetamide ophthalmic (Trimethoprim is NOT a sulfonamide, but it is included here due to its same mechanism of action=suppressing the synthesis of tetrahydrofolate AND is combined with sulfamethoxazole to form the medication Bactrim.) • Indications for use : Primarily used to treat UTIs. Other major uses are topical to treat superficial infections of the eyes & to suppress bacterial colonization in burns. Also useful for nocardiosis, Listeria species infection, & infection with P. jirovecii. Used as alternatives to doxycycline & erythromycin for infections caused by C. trachomatis. Used in conjunction with pyrimethamine to treat 2 protozoal infections: toxoplasmosis & malaria caused by chloroquine-resistant Plasmodium falciparum. Sulfasalazine is used to treat ulcerative colitis. • Contraindications & high-risk patients : Sulfonamides are contraindicated for nursing mothers, pregnant women in the 1st trimester & also those near term, & infants younger than 2 months. An alternative antibiotic must be chosen for patients with G6PD deficiency (can cause hemolytic anemia). Exercise caution in patients with renal impairment—may require a reduced dosage. Trimethoprim is contraindicated in patients with folate deficiency (manifested as megaloblastic anemia) & should be avoided when folate deficiency is likely (patients with alcoholism & pregnant women). • Monitoring needs : *CBC should be monitored if the patient develops signs or symptoms of blood disorders, as should CD4+ count for patients with HIV. *Signs & symptoms of hypersensitivity reactions & of resolution of infection should also be assessed. *If hyperkalemia is suspected due to use of trimethoprim, potassium must be checked 4 days after starting treatment. (p. 694) • Which ones require renal dosing adjustments and how much (i.e., 25%, 50%, etc.) : For patients with a creatinine clearance (CrCl) of 15-30 mL/min, providers should prescribe 50% of the typical recommended dose. If CrCl falls below 15 mL/min, drug must be discontinued (p. 694) *Bactrim • Patient education : *Instruct patients to complete the prescribed course of treatment even though symptoms may abate before the full course is over. *Patients taking oral sulfonamides should drink at least 8 to 10 glasses of water or other noncaffeinated fluids per day to decrease the risk for crystalluria. (Caffeine may be taken in addition to the other fluids). *To prevent photosensitivity reactions, advise patients to avoid prolonged exposure to sunlight, wear protective clothing, & apply sunscreen to exposed skin. Tanning beds should be avoided. *Patients should be instructed to observe for alterations that may indicate hypersensitivity & report these promptly if they occur. • Lifespan considerations : Infants: Use of sulfonamides in infants younger than 2 months can cause kernicterus (deposition of bilirubin in the brain—neurotoxic & can cause severe neurologic deficits & even death). Pregnant women: Systemic sulfonamides may cause birth defects, especially if taken during the 1st trimester. If taken near term, the infant may develop kernicterus. Breastfeeding women: Sulfonamides are secreted in breast milk. Breastfeeding women on sulfonamides should be warned that breastfeeding an infant younger than 2 months can cause kernicterus. Older adults: Older patients are more likely to experience adverse effects, & when experienced, the effects are more likely to be severe. Life-threatening effects—including neutropenia, Stevens-Johnson syndrome, & toxic epidermal necrolysis—occur more frequently in older adults. Fluoroquinolones (broad-spectrum agents with multiple applications against most aerobic gram-negative bacteria & some gram-positive bacteria; disrupt DNA replication & cell division; rapidly bactericidal) (p. 711) • Examples : Ciprofloxacin (Cipro), Levofloxacin (Levaquin), Ofloxacin (Floxin), Moxifloxacin (Avelox), Gemifloxacin, Delafloxacin • Indications for use : Approved for a wide variety of infections, including those of the respiratory tract, urinary tract, GI tract, bones, joints, skin, & soft tissues. Preferred drug for preventing anthrax in people who have inhaled anthrax spores. (Respiratory infections : moxifloxacin, gemifloxacin, levofloxacin; Urinary infections: ciprofloxacin, levofloxacin). • Contraindications & high-risk patients : Contraindicated in patients with a history of myasthenia gravis as they can exacerbate muscle weakness. Should be used with caution in patients with renal impairment, patients over 60 years old, & patients taking glucocorticoids. • Monitoring needs : None recommended. • Which ones require renal dosing adjustments and how much (i.e., 25%, 50%, etc.) : *Ciprofloxacin, Levofloxacin • Patient education : *Patients must be instructed to report early signs of tendon injury (pain, swelling, or inflammation) & to avoid prolonged sun exposure. (p. 713) *Take on an empty stomach with a full glass of water because food delays absorption. *May cause dizziness. • Lifespan considerations : (p. 712) Children/adolescents: Ciprofloxacin & levofloxacin are the only fluoroquinolones approved for use in children. Because of concerns regarding tendon injury, fluoroquinolones are generally avoided in this population. Pregnant women: Although data reveal little potential for fluoroquinolone toxicity in the fetus, these data are limited. Risks & benefits must be considered for administration during pregnancy. Breastfeeding women: Effects of fluoroquinolones on the nursing infant are largely unknown. Other medications should be considered if possible. Older adults: Fluoroquinolones are generally well tolerated in older adults. For safe dosing, creatinine clearance should be calculated. Macrolides (broad-spectrum antibiotics that inhibit bacterial protein synthesis by binding to the 50S ribosomal subunit; usually bacteriostatic, but can be bactericidal against highly susceptible organisms or when present in high concentrations) (pp. 678-679) • Examples : Erythromycin, Azithromycin, Clarithromycin • Indications for use : Treatment of respiratory infections, infections caused by H. pylori, disseminated Mycobacterium, & as an alternative to penicillin in patients with a penicillin allergy. 1st choice treatment for Corynebacterium diphtheriae, certain chlamydial infections (urethritis, cervicitis), & for pneumonia caused by Mycobacterium pneumoniae. (Whooping cough, diphtheria, respiratory tract, skin, chlamydia) • Contraindications & high-risk patients : *Use with caution in patients with QT prolongation. *Should be avoided by patients taking CYP3A4 inhibitors, including certain calcium channel blockers (verapamil & diltiazem), azole antifungal drugs (ketoconazole, itraconazole), HIV protease inhibitors (ritonavir, saquinavir), & nefazodone (an antidepressant). *Erythromycin can increase the plasma levels & half-lives of several drugs through inhibition of hepatic cytochrome P450 drug-metabolizing enzymes, thereby posing a risk for toxicity when taking theophylline (used for asthma), carbamazepine (used for seizures & bipolar disorder), & warfarin (an anticoagulant). (p. 679) • Monitoring needs : None recommended. • Which ones require renal dosing adjustments and how much (i.e., 25%, 50%, etc.) : *Clarithromycin • Patient education : GI disturbances can be reduced by administering with meals. • Lifespan considerations : Infants: Children/adolescents: Pregnant women: Breastfeeding women: Older adults: *Only use a macrolide in areas with pneumococcal resistance to macrolides <25% & when there are contraindications to alternative therapies. Patients with comorbidities or risk factors for drug-resistant pathogens : Comorbidities include : chronic heart, lung, liver, or renal disease; diabetes mellitus; alcohol abuse; malignancy; asplenia. Broader-spectrum antibiotic regimens are required in these patients as many will have risk factors for drug- resistant pathogens (e.g., recent hospitalization & administration of parenteral antibiotics in the past 90 days), & they are more vulnerable to poor outcomes if the empiric regimen is inadequate. Empiric oral antibiotics are recommended: combination therapy with amoxicillin/clavulanate or a cephalosporin (e.g., cefpodoxime, cefuroxime) plus a macrolide or doxycycline; or monotherapy with a respiratory fluoroquinolone (e.g., levofloxacin, moxifloxacin, gemifloxacin). These regimens should effectively cover drug-resistant pathogens. Combination Therapy : Amoxicillin/clavulanate 500 mg PO (immediate-release) TID; 875 mg PO (immediate-release) BID; 2000 mg PO (extended-release) BID OR Cefpodoxime proxetil 200 mg PO BID OR Cefuroxime axetil 500 mg PO BID AND Azithromycin 500 mg PO once daily on the 1st day, followed by 250 mg once daily thereafter OR Clarithromycin 500 mg PO (immediate-release) BID; 1000 mg PO (extended-release) once daily OR Doxycycline 100 mg PO BID Monotherapy: Levofloxacin 750 mg PO once daily OR Moxifloxacin 400 mg PO once daily OR Gemifloxacin 320 mg PO once daily ▪ Understand the use of macrolides in pregnancy & children under the age of 8 with CAP or M. Pneumoniae . Atypical pneumonia is more commonly seen in children & young adults. Mycoplasma pneumoniae is the typical causative organism, followed by Chlamydia pneumoniae & Legionella pneumoniae. L. pneumoniae is more common in areas where moisture levels are high & carries a higher mortality risk. These patients are less likely to have a fever & 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 & 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. Several infections respond equally well to macrolides & tetracyclines. Both drugs are 1st choice for pneumonia caused by Mycoplasma pneumoniae. As tetracyclines are contraindicated in pregnant women (animal studies reveal they can cause fetal harm in pregnancy) & in children younger than 8 years (may cause permanent discoloration of the teeth), macrolides would be the correct option for treating these special populations of patients. Erythromycin is generally free of serious toxicity & is considered one of the safest antibiotics. (pp. 678-679) ▪ When to prescribe fluoroquinolone for CAP Fluoroquinolones have been used; however, their use is discouraged unless the individual has been treated with an antimicrobial agent within the last 90 days that could increase the risk of a drug- resistant microbe. • Progression of infectious process ▪ Treatment expectations Chest x-ray in bacterial pneumonia will show consolidation in the affected lobe & should be repeated within 6 weeks of treatment to assure the infection was cleared. Treat for a minimum of 5 days. Duration of treatment should be guided by a validated measure of clinical stability (e.g., resolution of vital sign abnormalities, normal cognitive function, ability to eat). Consider discontinuing treatment when the patient has been afebrile for 48-72 hours & there are no signs of complications (endocarditis, meningitis). Sputum culture & sensitivity may be helpful if a patient is unresponsive to empirical treatment. Consider switching patients to an organism-specific antimicrobial therapy guided by antibiotic sensitivity in patients in whom laboratory tests have revealed a causative organism. Reassess patients at 48 hours. Symptoms should improve within this time with appropriate treatment. Consider hospital admission in patients who fail to improve within 48 hours. • Know the most likely pathogen causing CAP according to patient population 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) More common in areas where moisture levels are high • Legionella pneumoniae *Usually transmitted by inhaling mist or aspiration liquid that comes from a water source contaminated with Legionella. No evidence of person-to-person spread of the disease. Often seen in people who have recently spent extended time in proximity • Mycoplasma pneumoniae & Chlamydia pneumoniae *Mostly cough transmitted (closed communities : correctional facilities, college dormitories, long-term care facilities). -Treatment of chlamydial pneumonia (Epocrates) • A bacterial respiratory pathogen that is a frequent cause of community-acquired pneumonia in children & adults. • An obligate intracellular bacterium that can only be isolated in tissue culture, although culture is not widely available. Infection can be diagnosed using nucleic acid amplification tests & two FDA-approved commercial assays are now available. • Pneumonia due to Chlamydia pneumoniae cannot be differentiated clinically from pneumonia due to other atypical organisms, especially Mycoplasma pneumoniae. • Treatment with macrolides, fluoroquinolones, or tetracyclines appears to be equally efficacious. Adults: • Data on microbiologic efficacy based on culture are limited; the results of three published treatment studies in adults that used cultures demonstrated 70% to 80% eradication of Chlamydia pneumoniae from the respiratory tract in adults with community-acquired pneumonia after treatment with azithromycin, levofloxacin, or moxifloxacin. These three drugs appear to be equivalent & can be considered first-line. • Tetracyclines, specifically doxycycline, are also used first-line. • Tetracyclines & fluoroquinolones cannot be used in pregnant women. Treatment in this group should be with a macrolide (azithromycin, clarithromycin, or erythromycin). Azithromycin 500 mg PO once daily on day one, followed by 250 mg once daily for 4 days OR Levofloxacin 500 mg PO/IV once daily for 7-14 days OR Moxifloxacin 400 mg PO/IV once daily for 10 days OR Doxycycline 100 mg PO BID for 14-21 days OR Tetracycline 250 mg PO every 6 hours for 14-21 days OR Clarithromycin 250 mg PO BID for 10 days OR Erythromycin 500 mg PO every 6 hours for 14-21 days Children: • Treatment is with either a 10-day course of erythromycin or clarithromycin, or a 5-day course of azithromycin suspension. • All these regimens have demonstrated 80% efficacy in eradication of Chlamydia pneumoniae from the respiratory tract of children. Erythromycin 50 mg/kg/day PO given in divided doses every 6 hours for 10-14 days OR Clarithromycin 15 mg/kg/day PO given in divided doses every 12 hours for 10 days OR Azithromycin 10 mg/kg/day PO on day one, followed by 5 mg/kg/day for 4 days -Understand empiric treatment and when to use (Week 1 module) Although cultures are the most accurate way to identify pathogens, it is not always practical or economical to culture every infection. Sometimes the NP will start treatment without cultures or prior to receiving the results of a culture. This is referred to as empiric therapy. Empiric therapy is initiated based on the NP's knowledge of the patient's history, typical pathogens, gram stain results, & local susceptibility reports on which antibiotics work best in certain geographic locations. Targeted vs. Empiric therapy : Depends on the urgency of the patient's needs • 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 IV vs. PO? • How to treat Most cases of C. dif infection (CDI) can be managed well with antibiotics, usually vancomycin or metronidazole (Flagyl) plus vigorous fluid & electrolyte replacement. Treatment consists of stopping one antibiotic & starting another. ASAP after diagnosis of CDI, the antibiotic that facilitated C. dif overgrowth must be stopped because it will reduce the risk for reinfection after the CDI has cleared & in 25% of patients with mild CDI, it will cause the infection to resolve. At the same time, an antibiotic to eradicate C. dif should be started. For initial occurrences of mild to moderate CDI, treatment with PO vancomycin or fidaxomicin (a narrow spectrum macrolide) is recommended. If the infection is diagnosed as fulminant (characterized by the presence of shock, megacolon, or hypotension), PO vancomycin is preferred. Metronidazole can be used in situations where PO vancomycin or fidaxomicin is not available. Initial episode (mild or moderate) : Preferred drug therapy : Vancomycin 125 mg PO QID x 10 days OR Fidaxomicin 200 mg PO BID x 10 days Alternative drug therapy Metronidazole 500 mg PO TID x 10 days Initial episode (fulminant) : Preferred drug therapy : Vancomycin 500 mg PO QID x 10 days Alternative drug therapy Vancomycin 500 mg PR QID x 10 days in patients with ileus • Which antibiotics are more likely to cause? CDI is almost always preceded by the use of antibiotics, which kill off normal gut flora & allow C. dif to flourish. Antibiotics most likely to promote CDI are clindamycin, 2nd & 3rd generation cephalosporins, & fluoroquinolones. -Which antibiotics require renal dose adjustments? (https://fpnotebook.com/renal/pharm/DrgDsngInChrncKdnyDs.htm) Antibiotics that require NO renal dose adjustment : ▪ Azithromycin ▪ Ceftriaxone ▪ Clindamycin ▪ Doxycycline ▪ Linezolid ▪ Moxifloxacin ▪ Nafcillin ▪ Rifampin Agents to avoid in severe Chronic Kidney Disease : ▪ Penicillin G (Myoclonus, Seizures, coma risk) ▪ Imipenem with cilastin (Seizure risk); Meropenem safe ▪ Tetracycline (exacerbates Uremia); Doxycycline safe ▪ Nitrofurantoin (peripheral neurotoxicity) ▪ Aminoglycosides (or close level monitoring if used) Amoxicillin ▪ Reduce to every 24 hours if GFR<10 ml/min Augmentin ▪ Reduce to every 24 hours if GFR<10 ml/min ▪ Do not use Augmentin 875/125 mg tabs if GFR<30 ml/min Cefazolin ▪ Reduce to every 12 hours if GFR<50 ml/min ▪ Reduce to 50% every 24-48 hours if GFR<10 ml/min Cefuroxime ▪ Reduce to 250 to 500 mg every 24 hours if GFR<10 ml/min Cephalexin ▪ Reduce to every 12-24 hours if GFR<10 ml/min Ciprofloxacin ▪ Reduce dose to 50-75% if GFR<50 ml/min ▪ Reduce dose to 50% or change to once daily dosing if GFR<10 ml/min Clarithromycin ▪ Reduce dose to 50-100% if GFR<50 ml/min ▪ Reduce dose to 50% or change to once daily dosing if GFR<10 ml/min Penicillin ▪ Reduce to 50% if GFR <30 ml/min Levofloxacin ▪ Reduce to every 24-48 hours if GFR<50 ml/min (or 500 mg loading dose, then 250 mg for subsequent doses) ▪ Reduce to every 48 hours if GFR<20 ml/min ▪ Avoid if GFR<10 ml/min Trimethoprim-Sulfamethoxazole (TMP-SMZ, Septra, Bactrim) ▪ Reduce to 50% if GFR <30 ml/min ▪ Avoid if GFR<15 ml/min Vancomycin ▪ Adjust dosing intervals based on drug level and Creatinine Clearance What types of infections are usually viral and do not warrant antibacterial agents? (Week 1 module) Avoid antibiotic treatment for community-acquired, mostly viral, upper respiratory tract infections. Week 2 Fungal infections can be categorized as either systemic or superficial. Although systemic infections occur less frequently, they are more serious & can be life-threatening. Understanding the appropriate drug choice for each type of fungal infection is an essential element of safe prescribing. Systemic fungal infections are classified as either opportunistic or non-opportunistic. Opportunistic infections are much more common & are found in patients who are immunocompromised. Fungi that cause systemic opportunistic infections include: Candidiasis, Aspergillosis, Cryptococcosis, & Mucormycosis. Systemic antifungal drugs fall into 4 classes : ▪ Polyene antibiotics : Amphotericin B *Drug of choice for most systemic mycoses! (highly toxic & must be given IV) MOA: Bind to ergosterol & disrupt the fungal cell membrane. ▪ Azoles : Fluconazole, Isavuconazonium, Itraconazole, Ketoconazole, Posaconazole, Voriconazole *Alternative to Amphotericin B for most systemic fungal infections (lower toxicity & can be given PO) MOA: Inhibit synthesis of ergosterol & disrupt the fungal cell membrane. ▪ Echinocandins : Anidulafungin, Caspofungin, Micafungin *Newest class of antifungals, IV only, use limited mainly to Aspergillus & Candida species MOA: Inhibits synthesis of 𝗉-1,3-d-glucan & disrupt the fungal cell wall. ▪ Pyrimidine analogs : Flucytosine *Used for serious infections caused by susceptible strains of Candida & Cryptococcus only MOA: Disrupt the synthesis of RNA & DNA. -Know how to treat: • Different types of Tinea : (pp. 719-720) Dermatophytic infections are commonly referred to as ringworm. There are 4 principle dermatophytic infections, defined by their location: tinea pedis (ringworm of the foot AKA “athlete’s foot”), tinea corporis (ringworm of the body), tinea cruris (ringworm of the groin), & tinea capitis (ringworm of the scalp). o Tinea pedis : The most common fungal infection, generally responds well to topical therapy. Patients should be advised to wear absorbent cotton socks, change their shoes often, & dry their feet after bathing. o Tinea corporis : Usually responds to a topical azole or allylamine. Treatment should continue for at least 1 week after symptoms have cleared. Severe infection may require a systemic antifungal agent (griseofulvin). o Tinea cruris : Responds well to topical therapy. Treatment should continue for at least 1 week after symptoms have cleared. If the infection is severely inflamed, a systemic antifungal drug (clotrimazole) may be needed; topical or systemic glucocorticoids may be needed as well. o Tinea capitis : Difficult to treat. Topical drugs are not likely to work. Oral griseofulvin, taken for 6 to 8 weeks, is considered standard therapy. However, oral terbinafine, taken for only 2 to 4 weeks, may be more effective. Tinea pedis, tinea corporis, & tinea cruris : • Apply topical agents once or twice daily until no further infection is visible for 1-2 weeks, generally a total treatment time of 2-6 weeks. • In tinea pedis, the most effective topical agents are the allylamines. Allylamine agents include terbinafine & naftifine (which seem to be equally effective) & butenafine. Topical allylamine antifungal therapy : Terbinafine topical (1%)-children >12 y.o. & adults: apply to the affected area(s) BID x 1-3 weeks OR Naftifine topical (1% gel)-adults: apply to the affected area(s) BID for up to 4 weeks; (1% cream)-adults: apply to the affected area(s) once daily for up to 4 weeks; (2% cream or gel)-adults: apply to the affected area(s) once daily x 2 weeks OR Butenafine topical (1%)-children >12 y.o. & adults: apply to the affected area(s) once or twice daily x 1-2 weeks Topical azole antifungal therapy : Miconazole topical (2%)-children >2 y.o. & adults: apply to the affected area(s) BID x 2-4 weeks OR Clotrimazole topical (1%)-children >2 y.o. & adults: apply to the affected area(s) BID x 2-4 weeks OR the solution immediately. Also inform patient about early signs of neuropathy (numbness, tingling, or pain in hands & feet) & instruct them to report these immediately. Zidovudine: Instruct patients to report new or worsening symptoms of anemia (pallor, weakness) or neutropenia (evidence of infection). To prevent exposure to illness, patients should be cautioned to avoid contact with people who are ill & to avoid areas where people may congregate in large numbers. -Diagnostics & Monitoring for anthelmintics Helminths are parasitic worms, & anthelmintics are the drugs used against them. The intestine is a frequent site of infestation, but other sites include the liver, lymphatic system, & blood vessels. Infestation is frequently asymptomatic, but can sometimes cause severe complications. Helminthiasis is most prevalent where sanitation is poor. 3 classes of parasitic worms : (pp. 771-773) o Nematodes (Roundworms): those that infest the intestinal lumen & those that inhabit tissue ▪ Nematode Infestations (Intestinal) 𝗌 Ascariasis (Giant Roundworm Infestation) 𝗌 Enterobiasis (Pinworm Infestation) 𝗌 Ancylostomiasis & Necatoriasis (Hookworm Infestation) 𝗌 Trichuriasis (Whipworm Infestation) 𝗌 Strongyloidiasis (Threadworm Infestation) ▪ Nematode Infestations (Extraintestinal) 𝗌 Trichinosis (Pork Roundworm Infestation) 𝗌 Wuchereriasis & Brugiasis (Lymphatic Filarial Infestation) 𝗌 Onchocerciasis (River Blindness) o Cestodes (Tapeworms) 𝗌 Taeniasis (Beef & Pork Tapeworm Infestation) 𝗌 Diphyllobothriasis (Fish Tapeworm Infestation) o Trematodes (Flukes) 𝗌 Schistosomiasis (Blood Fluke Infestation) 𝗌 Fascioliasis (Liver Fluke Infestation) 𝗌 Fasciolopsiasis (Intestinal Fluke Infestation) 8 drugs of choice for Helminthiasis (Anthelmintics) : (p. 773) • Albendazole, Diethylcarbamazine, Ivermectin, Mebendazole, Moxidectin, Praziquantel, Pyrantel pamoate, Triclabendazole Baseline Data : Confirmation of infestation. Pregnancy test. Drugs requiring additional baseline data: Albendazole (liver function & CBC w/differential) Mebendazole (liver function, CBC w/differential, & renal function) Praziquantel (liver function) Ivermectin & Moxidectin (ophthalmologic exam for evidence of eye infestation) Monitoring: Drugs requiring monitoring (other than confirmation of a cure, if needed) are: Albendazole (liver function & CBC w/differential) Mebendazole (liver function, CBC w/differential, & renal function) Praziquantel (liver function) Ivermectin & Moxidectin (ophthalmologic exam if abnormal at baseline) -Identifying High-Risk Patients with the following drugs Anthelmintics for parasitic worms (p. 775) • Albendazole—Because bone marrow suppression, impaired liver function, & possibly renal function may occur, patients with liver or kidney disease, anemia, bleeding disorders, & infections are at increased risk. • Mebendazole—Because bone marrow suppression & liver impairment may occur, patients with liver disease, anemia, bleeding disorders, & infections are at increased risk. • Pyrantel pamoate—Patients with liver impairment are at a higher risk for adverse effects. Neonates should not be prescribed formulations containing benzyl alcohol or its derivatives (can develop a potentially fatal “gasping syndrome” with complications that include respiratory distress, cardiovascular collapse, seizures, & metabolic acidosis). • Ivermectin—Patients with hypotension or taking antihypertensive drugs may be at risk for increased hypotension & falls. • Moxidectin—Patients with hypotension or taking antihypertensive drugs may be at risk for increased hypotension & falls. Nucleotide Reverse Transcriptase Inhibitors (NRTIs) for HIV infection (p. 762) • Didanosine—Risk for pancreatitis is increased by a history of alcoholism or pancreatitis & by use of IV pentamidine. • Zidovudine—Risk for hematologic toxicity is increased by a low granulocyte count; low levels of hemoglobin, vitamin B12, or folic acid; & concurrent use of drugs that are myelosuppressive, nephrotoxic, or toxic to circulating blood cells. Protease Inhibitor for HIV infection • Lopinavir—*Lopinavir/ritonavir oral solution is contraindicated for full-term infants (until 14 days after birth) & preterm infants (until 14 days after their predicted due date. *Use with caution in patients with structural heart disease, cardiac conduction disturbances, & ischemic heart disease, & in those taking other drugs that prolong the PR interval. *Avoid in patients with congenital long QT syndrome, & in those taking drugs that prolong the QT interval. -Adverse Effects Anthelmintics for parasitic worms (pp. 773-775) • Albendazole—Generally well tolerated. *Mild to moderate liver impairment has occurred in 16% of patients. Liver function should be assessed before each cycle of treatment & 14 days later. *Suppresses bone marrow function & therefore can cause granulocytopenia, agranulocytosis, & even pancytopenia. Liver impairment may increase risk. Blood cell counts should be obtained before each cycle of treatment & 14 days later. *Is teratogenic in animals, so should not be used during pregnancy. If pregnancy occurs, the drug should be discontinued immediately. • Mebendazole—Systemic effects are rare at usual doses. *The most concerning are bone marrow suppression & liver impairment, however these are typically only a problem with high doses or prolonged treatment. *In patients with massive parasitic infestations, transient abd pain & diarrhea may occur. • Pyrantel pamoate—*Neonates given formulations with benzyl alcohol or its derivatives had developed a potentially fatal “gasping syndrome” with complications that include respiratory distress, cardiovascular collapse, seizures, & metabolic acidosis. *Otherwise, serious reactions are rare. *The most common effects are GI reactions (N/V/D, abd pain, & cramps). *Possible central nervous system effects include dizziness, drowsiness, headache, & insomnia. • Ivermectin--*Patients treated for onchocerciasis (a major cause of blindness worldwide) commonly develop pruritus, rash, fever, lymph node tenderness, & bone & joint pain. This reaction, known as a Mazotti reaction, is an allergic & inflammatory response to the death of O. volvulus rather than a reaction to the drug. *Abdominal pain & headache are seen in less than 5% of patients. *Hypotension develops rarely. *Ivermectin is teratogenic in mice, rats, & rabbits—cleft palate is the most common effect. There are no adequate data of teratogenesis in humans, so this medication should be avoided during pregnancy. • Moxidectin—*Patients typically experience the flu-like symptoms of the Mazotti-response associated with death of the microfilariae during the first week. Adverse effects mirror those of ivermectin. *Early studies suggest that a major advantage over ivermectin is moxidectin’s apparent decreased risk for teratogenesis, however human studies are lacking so we do not have enough data yet to determine if this med is safe to take during pregnancy. Protease Inhibitors for HIV infection (p. 756) • Lopinavir/ritonavir—BLACK BOX WARNING: Dangerous drug interactions (with drugs that inhibit or induce P450 enzymes & with drugs that are substrates for P450 enzymes), hepatotoxicity, pancreatitis, PR interval prolongation, QT interval prolongation, hyperglycemia or diabetes (new onset or exacerbation), immune reconstitution syndrome, redistribution of adipose tissue, hyperlipidemia, renewed bleeding in patients with hemophilia, headache, N/V, abd pain, indigestion, weakness. • Saquinavir—BLACK BOX WARNING: Dangerous drug interactions (including danger with ritonavir), PR interval prolongation, QT interval prolongation, diabetes (new onset or exacerbation), immune reconstitution syndrome, redistribution of adipose tissue, renewed bleeding in patients with hemophilia, exacerbation of comorbid hepatic disease, hyperlipidemia, N/V/D, abd pain, fatigue. HIV Fusion Inhibitor for HIV infection • Enfuvirtide—BLACK BOX WARNING: *Injection site reactions in 98% of patients, usually within the 1st week of treatment (pain & tenderness, erythema & induration, nodules or cysts, pruritus, & ecchymosis) that are generally mild to moderate, but can also be severe. *Hypersensitivity reactions (rash, fever, N/V, chills, rigors, hypotension, & elevated serum transaminases). *Has also been associated with respiratory distress, glomerulonephritis, Guillain-Barré syndrome, & primary immune complex reaction, all of which may be immune mediated. *Increases the risk for bacterial pneumonia, so use with caution in patients who have increased risk factors (low initial CD4 cell counts, high initial viral load, IV drug use, smoking, & a history of lung disease). -Lifespan Considerations • Which medications are safe during pregnancy or childhood? Antifungal Agents : (p. 718) Infants: Nystatin is used to treat oral candidiasis in premature & full-term infants. Fluconazole is also used safely to treat systemic candidiasis in newborn infants. Children/adolescents: Many antifungal agents are used safely in children, in lower doses. Side-effect profiles are similar to those of adults. Pregnant women: Risks & benefits must be considered for administration during pregnancy. Systemic Drugs for Herpesvirus & Varicella Zoster Virus Infections : (p. 724) Children: Acyclovir is approved for children as young as 3 months of age. Valacyclovir is approved for children 2 years of age. The safety & efficacy of foscarnet have not been established for children. The efficacy of famciclovir in children has not been established. Pregnant women: Epidemiologic reviews of the use of acyclovir, famciclovir, & valacyclovir in pregnant women did not find a significant increase in abnormal outcomes compared with the general population. Foscarnet, which is deposited in bone & teeth, has caused abnormal development of tooth enamel in animal studies & therefore is not recommended during pregnancy. Antiviral Drugs for Influenza : (pp. 742-743) Children: Oseltamivir (Tamiflu) is approved for the prevention & treatment of influenza in patients 1 year of age & older. Zanamivir (Relenza) is approved for treatment of acute uncomplicated influenza in patients at least 7 y.o. & for prophylaxis in patients at least 5 y.o. Baloxavir marboxil (Xofluza) may be used in patients 12 y.o. & older. Pregnant women: Because of the harmful effects of influenza on the developing embryo & fetus, the American College of Obstetricians & Gynecologists (ACOG) recommends oseltamivir for both prophylaxis & treatment in pregnant women. The ACOG recommends zanamivir for pregnant women, however if there is an option to give oseltamivir, it is preferred. At this time, there is not enough data to adequately determine safety for the use of baloxavir marboxil in pregnancy. Treatment: All children with AOM should receive pain medication, & some should receive antibiotics. Prescribing antibiotics for all children should be discouraged because most (over 80%) of AOM episodes resolve spontaneously within a week. Current guidelines recommend OBSERVATION (management of symptomatic relief alone for 48-72 hours), then if symptoms persist or worsen, antibacterial therapy is initiated. *All children younger than 6 months should receive antibiotics, regardless of diagnostic certainty or symptom severity. *Children 6 months to 2 years: antibiotics indicated if diagnosis is certain OR illness is severe; if not then observation. *Children 2 years & older: antibiotics indicated if diagnosis is certain AND illness is severe; otherwise observation, regardless of symptom severity. o High-dose Amoxicillin is the treatment of choice (40-45 mg/kg BID x 5-10 days) o Non-severe (Type II) PCN allergy: Cephalosporin (Cefdinir, Cefuroxime) o Severe (Type I) PCN allergy: Azithromycin, Clarithromycin o Treatment of Antibiotic-Resistant AOM: High-dose Amoxicillin/Clavulanate o Non-severe (Type II) PCN allergy: Ceftriaxone o Severe (Type I) PCN allergy: Clindamycin -Treatment of Otitis Externa and associated symptoms (pp. 853-855) Symptoms of Acute Otitis Externa (AOE): “Swimmer’s ear”; patients present with 1 or more of the following: rapid-onset ear pain associated with pruritus, a sensation of ear fullness, tenderness on manipulation of the external ear, or edema or erythema of the external ear canal (EAC); impaired hearing & purulent discharge may occur. Treatment: The same analgesics used for AOM are appropriate for AOE pain management. For most patients, cleaning & using topical antibiotics will suffice. If the infection is extensive, oral antibiotics may be needed. *First line treatment is a topical 2% solution of acetic acid (alternative solution of alcohol plus acetic acid given additional benefit of promoting tissue drying. *For more extensive or resistant AOE, a topical antibiotic is indicated: Ciprofloxacin/dexamethasone otic drops (0.3%/0.1%) includes glucocorticoid with added benefit of decreasing pain by reducing swelling caused by inflammation. (If edema results in EAC closure that is sufficient to impede drug penetration, insertion of an ear wick can facilitate medication delivery—apply enough medication to exposed tip to keep the wick moist & replace at least every 48 hours). *Oral antibiotics indicated if the infection has spread beyond the EAC to involve the pinna OR in patients with diabetes, immune deficiencies, or those who would have difficulty with proper administration of topical drugs. (Adults: Ciprofloxacin; Children: Cephalexin) *10% of cases are Fungal Otitis Externa (Otomycosis) : Presents as intense pruritis & erythema, with or without pain or hearing loss. First line treatment is the same topical 2% solution of acetic acid 3-4x/day for 7 days. If these measures prove inadequate: antifungal solution 1% clotrimazole BID x 7 days. If unsuccessful, oral antifungal therapy may be needed: itraconazole or fluconazole. *First line analgesics for AOM with mild to moderate pain is acetaminophen & ibuprofen. *For moderate to severe pain, codeine & similar drugs may be needed. *For children older than 5 years, a topical anesthetic such as procaine or lidocaine drops is recommended (contraindicated if the TM is perforated!) (p. 850) Otitis Media (Middle Ear Infection) Otitis Externa (Swimmer’s Ear) Otomycosis (Fungal Ear Infection) Presumptive AOM: • Pain control 2-3 days - if symptomatic after 3 days, then start ABX Confirmed AOM: • Pain control & ABX therapy 1st line: Tylenol (kids: 10-15mg/kg q 4-6 hours) or Ibuprofen (kids 5- 10mg/kg q 6-8 hours) 1st: Amoxicillin OR Augmentin 2nd: Cefdinir OR Cefuroxime 3rd: Azithromycin OR Ceftriaxone Bacterial: Initial Tx, NON perforated 1st line: Ciprofloxacin/dexamethasone otic Tympanic Membrane drops (0.3%/0.1%) 1st line: 4 drops in affected ear(s) twice daily x 7-10 Hydrocortisone/acetic acid otic day drops OR (1%/2%) children ≥3 years of age Ofloxacin otic drops (0.3%) -5 drops into and adults: 3-5 drops into the affected ear(s) once daily x 7 days affected ear(s) three times daily (for pt’s over 6 months of age) for 7-10 days OR ADULTS: 10 drops into affected ear(s) once daily for 7 days Acetic Acid Otic Drops (2%) children and adults: 3-5 drops into the affected ear(s) three times daily for 7-10 days PERFORATED Tympanic Membrane Tolnaftate Otic Drops (1%) children ≥2 years of age and adults: 3-4 drops into the affected ear(s) three to four times daily for 7 days • Delayed therapy is an option in healthy patients 6 months or older with reliable follow-up, • Initial treatment refers to otherwise healthy people without any extension to the outside ear canal. • Frequent cleaning by medical professionals is necessary. Prior to the use of topical ear drops, particularly patients who do not meet the diagnostic criteria or have a less certain diagnosis. • A recommended approach is to provide analgesia and observe for 2 to 3 days. If the patient remains symptomatic after the observation period ends, the antibiotic is started. This approach may reduce the number of unnecessary antibiotic courses, decrease the occurrence of adverse antibiotic reactions, improve the benefit provided by antibiotics, and reduce healthcare expenditures. Children under 2 years of age and with bilateral disease or who have severe tympanic membrane bulging may respond less well with this approach. • Prior to the use of topical ear drops, the ear canal needs to be cleaned of any debris or wax. • Patients who have severe swelling of the ear canal may have difficulty applying ear drops. A wick should be inserted in the ear canal to allow for drug delivery. • Ciprofloxacin/dexamethasone and ofloxacin can be used in patients with perforated tympanic membranes. • Ototoxic ear drops (those that contain aminoglycosides and alcohol) should be avoided in patients with possible tympanic perforations the ear canal needs to be cleaned of any debris or wax. • Patients who have severe swelling of the ear canal may have difficulty applying ear drops. A wick should be inserted in the ear canal to allow for drug delivery. • Oral antifungals may be used if caused by candida infection. Further studies are needed to assess the benefit of oral antifungal agents in otomycosis. Dose and duration of treatment for such an indication have not been fully studied. Itraconazole may be used if caused by Aspergillus infection. -Treatment of acne (pp. 835-841) When evaluating acne, we should note its severity, distribution, & type of lesions: *Severity: can be mild, moderate, or severe. *Distribution: lesions typically develop on the face, neck, chest, shoulders, & back. *Type of lesions: –Open comedones (blackheads) are the most common—forms when sebum combines with keratin to create a plug within a pore; oxidation of the sebum causes the exposed surface of the plug to turn black. – Closed comedones (whiteheads) develop when pores become blocked with sebum & scales below the skin surface. – Abscesses & inflammatory cysts is most severe form of acne known as severe nodulocystic acne vulgaris. • Mild : *Nonpharmacological measures include reducing surface oiliness by cleansing with a gentle nonirritant soap a couple of times per day, avoiding irritation from vigorous scrubbing, avoiding oil-based makeup & moisturizers, comedo extraction & dermabrasion. *Pharmacological treatment= topical antibiotics (Benzoyl peroxide, Clindamycin, Dapsone, Erythromycin) & topical retinoids (Adapalene, Tazarotene, Tretinoin). • Moderate : *Can be treated with oral antibiotics (doxycycline, minocycline) & topical comedolytics (retinoids & keratolytics: Azelaic acid, Salicylic acid) • Severe (two agents) : *Can be treated with oral antibiotic PLUS topical combination therapy (antibiotic + retinoid) OR oral Isotretinoin *Monotherapy with either topical Clindamycin or Erythromycin quickly leads to drug resistance. To protect against this, there drugs can be combined with Benzoyl peroxide. 2 fixed-dose combinations are available: clindamycin/benzoyl peroxide & erythromycin/benzoyl peroxide. Latano prost (Xalatan), Travo prost (Travatan) , Bimato prost (Lumigan) , Latano prost ene bunod (Vyzulta) , Taflu prost (Zioptan) : Approved for topical therapy of glaucoma; are as effective as the beta-blockers & cause fewer side effects. Considered first-line medications for glaucoma. Lowers IOP by facilitating aqueous humor outflow, in part by relaxing the ciliary muscle. (pp. 825-826) o Adverse effects: Most significant side efect is a harmless heightened brown pigmentation of the iris that stops progressing when the med is stopped but does not usually regress. Can also increase pigmentation of the eyelid & may increase the length, thickness, & pigmentation of the eyelashes. Other side efects include blurred vision, burning, stinging, conjunctival hyperemia, conjunctival edema, & punctuate keratopathy. Rarely causes macular edema. o Patient teaching: For all topical glaucoma meds—*It is important to take the prescribed medications according to schedule. If days are skipped or if prescriptions are not refilled, loss of vision may occur. *Notify the provider immediately if experiencing vision loss, severe eye pain, headache, or N/V. These could indicate angle-closure glaucoma. *If photophobia is a problem outdoors, sunglasses, wide- brimmed hats, visors, or baseball caps may be helpful. *Take care not to touch the dropper to the eyes & not to touch the tip with your fingers. Contamination can cause an eye infection. *To improve topical absorption & minimize systemic absorption, close the eye(s) for 3 minutes after administering the eye drop(s) & lightly press a thumb or finger over the medial canthus (inner corner of the eye). • Salicylic Acid for Acne : A topical keratolytic drug for mild to moderate acne; promotes shedding of the outermost layer of the epidermal skin cells. (p. 839) o Adverse effects: Adverse efects such as local irritation & peeling are usually mild. However, if acne is extensive & the drug is applied to the trunk, back, & other locations, salicylate toxicity may occur (hyperpnea, tinnitus, N/V, & mental status changes). o Patient teaching: For all topical acne meds—*Can increase the risk for sunburn; avoid exposure to sunlight, sunlamps, & tanning beds during treatment. *Avoid irritant soaps & scrubs. *Wash & dry skin before applying med & then wash hands afterwards. *Keep the drug away from the eyes, mouth, & mucous membranes as well as inflamed, denuded, or sunburned skin. *Some drying, slight burning, & peeling is expected; however, report severe irritation such as blistering, intense burning, or swelling. A dosage adjustment or a diferent drug may be necessary. • Benzoyl peroxide : A first-line topical drug for mild to moderate acne; is both an antibiotic & keratolytic. Benefits derive primarily from suppressing the growth of P. acnes, but also reduces inflammation & promotes keratolysis (peeling of the horny layer of the epidermis). (p. 837) o Adverse effects: May produce drying & peeling of the skin. Has been associated with potentially serious hypersensitivity reactions in patients with asthma. o Patient teaching: For all topical acne meds—*Can increase the risk for sunburn; avoid exposure to sunlight, sunlamps, & tanning beds during treatment. *Avoid irritant soaps & scrubs. *Wash & dry skin before applying med & then wash hands afterwards. *Keep the drug away from the eyes, mouth, & mucous membranes as well as inflamed, denuded, or sunburned skin. *Some drying, slight burning, & peeling is expected; however, report severe irritation such as blistering, intense burning, or swelling. A dosage adjustment or a diferent drug may be necessary. • Isotretinoin (Accutane ): A Vitamin A derivative that is highly effective when used to treat severe nodulocystic acne vulgaris. For most patients, a single course of therapy can produce complete & prolonged remission. Decreases sebum production, sebaceous gland size, inflammation, & keratinization. (pp. 840-841) o Adverse effects: *BLACK BOX WARNING—carries a high risk of severe structural & cognitive defects in the developing fetus. It is also associated with an increased risk for spontaneous abortion. *Most common reactions are nosebleeds; inflammation of the lips; inflammation of the eyes; & dryness or itching of the skin, nose, & mouth. *Some patients experience pain, tenderness, or stifness in muscles, bones, & joints. *Other reactions include skin rash, headache, hair loss, & peeling of skin from the palms & soles. *Reduction of night vision has occurred, sometimes with sudden onset. *Increases the risk for several significant problems including pseudotumor cerebri (benign elevation of intracranial pressure), pancreatitis, hearing impairment (with or without tinnitus), decreased bone mineral density, & mental ▪ Intranasal antihistamines (e.g., azelastine, olopatadine) are particularly effective for rhinorrhea and nasal congestion, but they do not improve symptoms at non-nasal sites. ▪ They have a fast onset of action after initial dosing (usually 15 to 30 minutes, and no later than 3 hours) and are effective over a 12-hour period, but they may cause ▪ Oral antihistamines reduce sneezing, rhinorrhea, and itching of the nose, palate, and eyes. However, they only have a modest effect on nasal congestion ▪ Second-generation oral antihistamines are preferred to first-generation agents because they cause less or no sedation. Cetirizine has been found to be particularly effective in AR. ▪ Sedation is possible with cetirizine and levocetirizine; unlikely with loratadine, desloratadine, and fexofenadine; and likely with chlorpheniramine and diphenhydramine. ▪ There is a risk of paradoxical hyperactivity with use of sedating antihistamines, particularly in children. ▪ Allergen avoidance should be attempted by all patients with AR. Allergy testing can be helpful in identifying the relevant allergens of concern for a particular patient. health changes, including depression with SI. *Triglyceride levels may become elevated. *Adverse efects can be increased if also using tetracyclines and/or Vitamin A. o Patient teaching: *This drug may afect vision in the dark, therefore avoid driving at night if this afects you. *You may sunburn easily; protect skin from sunlight & avoid sunlamps & tanning beds. *Your provider will need you to come in periodically for blood tests & other assessments. *Women who can become pregnant should use 2 kinds of reliable birth control; notify your provider if you miss a period. *You cannot donate blood while taking this med & for 1 month after you stop. *Avoid alcohol & supplements containing Vitamin A. *Scarring may occur if you have cosmetic skin procedures while taking this drug & up to 6 months after stopping. Avoid waxing, laser therapy, dermabrasion, or similar procedures. *It is important to notify your provider of ANY new problems that develop while taking this drug. It is especially important to report the following—Severe headaches, vision changes (other than decreased night vision), vomiting, weakness, or seizures as these may be signs of increased pressure in the brain. –Symptoms of depression or thoughts of harming yourself or others. –Problems obtaining or maintain an erection. -Be familiar with which medications control which set of symptoms: • Intranasal glucocorticoids , such as fluticasone propionate, are the most effective drugs for prevention and treatment of seasonal and perennial symptoms because they prevent or suppress all the major symptoms of allergic rhinitis (congestion, rhinorrhea, sneezing, nasal itching, and erythema). • Pseudoephedrine is an oral sympathomimetic used to reduce nasal congestion associated with allergic rhinitis. It has no effect on other symptoms. • Loratadine, an oral antihistamine , reduces sneezing, rhinorrhea, and nasal itching only and is less effective than intranasal glucocorticoids. • Intranasal cromolyn sodium is moderately effective in the treatment of allergic rhinitis, but the benefits are much less than those of intranasal glucocorticoids. -Know treatment for allergic rhinitis • 1st - Intermittent Mild Symptoms: o Oral antihistamine + allergen avoidance ▪ Cetirizine/Desloratadine/Fexofenadine/Loratadine o Intranasal antihistamine + allergen avoidance ▪ Azelastine nasal/Olopatadine nasal • Naltrexone/Bupropion (Contrave) : A combination product approved for weight loss. Combines the effects of a dopamine & norepinephrine-reuptake inhibitor with an opioid antagonist. (p. 634) o Adverse effects: *The most common adverse reactions are N/V, constipation, headache, dizziness, & insomnia. *Some patients also experience an increase in blood pressure, dry mouth, diarrhea, abd pain, anxiety, & fatigue. *BLACK BOX WARNING—This med is associated with an increased risk for SI & suicide attempts in children, adolescents, & young adults. *BLACK BOX WARNING—When this med is given to patients who are taking or discontinuing bupropion, severe neuropsychiatric reactions have occurred, including depression, mania, psychosis, & homicidal ideation. o Patient teaching: *This med should not be used for weight loss in patients with uncontrolled HTN, seizure disorders, or eating disorders such as anorexia or bulimia. *Patients who are undergoing alcohol, barbiturate, or benzodiazepine withdrawal should not take this drug. *This med should not be taken within 2 weeks of MAOIs. *Bupropion has several indications for use: major depressive disorder, prevention of seasonal affective disorder (SAD), smoking cessation. Unlabeled uses include relief of neuropathic pain, treatment of depressive episodes in bipolar disorder, & management of ADHD. (p. 226) -Drug Interactions • Orlistat : *Because med can reduce absorption of fat-soluble vitamins & Vitamin K deficiency can intensify the efects of Warfarin, patients taking Warfarin should monitor for anticoagulant efects & take a daily multivitamin 2 hours before or after taking Orlistat. *Can cause hypothyroid in patients taking levothyroxine, so take meds at least 4 hours apart. *Can reduce absorption of cyclosporine, so take meds at least 3 hours apart. (pp. 631-632) • Lorcaserin : *Risk for serotonin syndrome is associated with serotonergic drugs, so caution & close monitoring are advised when this drug is taken w/other serotonergic drugs (bupropion, dextromethorphan, MAOIs, SNRIs, SSRIs, St. John’s wort, & triptans). *Lorcaserin is an inhibitor of the CYP2D6 isoenzyme of cytochrome P450. When given for CYP2D6 substrates (drugs metabolized by CYP2D6 isoenzymes), the serum levels of the substrates can be increased. To decrease the risk for toxicity, the substrate may have to be prescribed at a lower dose. (p. 633) -Baseline data and ongoing assessment needs for prescribing (pp. 635-636) • Liraglutide (Saxenda ) : Promotes satiety; slows gastric emptying, promoting a sense of fullness. o Side Effects: *N/V/D, elevated heart rate, hypoglycemia (in patients w/diabetes). o Baseline Data: *HbA1C, lipids, renal function. *Assessment of ability of patient or family to administer injections. o Special Monitoring Needs: *HbA1C every 6 months if stable—more often PRN; periodic monitoring of triglycerides, if indicated. *Assess for s/s of cholecystitis, pancreatitis, depression, & suicidal thoughts. • Orlistat (Alli, Xenical) : o Baseline Data: N/A o Special Monitoring Needs: *Assess for s/s of deficiency in fat soluble vitamins (Vitamins A, D, E, & K). *Monitor for s/s of liver damage (itching, vomiting, jaundice, anorexia, fatigue, dark urine, & light- colored stools. • Phentermine (Adipex-P, Lomaira) : o Baseline Data: *Cardiac assessment. o Special Monitoring Needs: *Ongoing assessment of cardiac status. • Naltrexone/bupropion (Contrave) : o Baseline Data: *Blood glucose, liver function, renal function, & mental status. o Special Monitoring Needs: *Periodic assessment for blood glucose, liver & renal function, s/s of depression, anxiety or panic attacks, suicidal ideation, & mania. -Role of topiramate in the treatment for obesity (p. 634) Topiramate is currently approved for seizure disorders & the prophylaxis of migraines. It induces a sense of satiety, possibly through the antagonism of glutamate (an excitatory neurotransmitter), modulation of receptors for - aminobutyric acid, & inhibition of carbonic anhydrase. It is used for weight loss when given in a combination product with phentermine. -Obesity stages (p. 629) • Stage 0 : A BMI of 25 or more with no complications o Lifestyle therapy o Drug therapy to be considered if lifestyle therapy alone is ineffective • Stage 1 : A BMI of 25 or more in the presence of one or more mild to moderate complications amenable to moderate weight loss o Lifestyle therapy o Drug therapy to be considered if lifestyle therapy alone is ineffective or if BMI is 27 or more • Stage 2 : A BMI of 25 or more & at least one complication requiring significant weight loss o Lifestyle therapy o Drug therapy to be considered for BMI of 25-26 o Drug therapy to be initiated for BMI of 27 or more o Bariatric surgery to be considered for BMI of 35 or more Components of Lifestyle Therapy • Food Intake : o Healthy intake at 500-700 kcal deficit daily. o Individualize intake according to personal & cultural preferences. o Preferred meal plans include the DASH diet; Mediterranean diet; low-carb, low-fat, high-protein diet; vegetarian diet; & volumetric diet. o Optional meal plans include meal replacements & very low-calorie diets (under supervision) • Physical Activity : o Reduce sedentary activity. o Individualize activity according to personal preferences & physical ability. o At least 150 minutes of aerobic activity 3-5 days per week. o Resistance exercises 2-3 times per week. • Behavior : o Self-monitor intake, weight, & activity. o Set goals. o Become educated using reliable resources. o Obtain counseling & treatment if needed. o Make use of social support. -DEA Schedules of drugs used to treat obesity (pp. 635-636) All DEA regulated drugs used to treat obesity are Schedule IV medications : • Lorcaserin • Diethylpropion • Phentermine • Phentermine/Topiramate Uncontrolled drugs used to treat obesity : • Liraglutide • Orlistat • Bupropion/Naltrexone Prescription Writing -Medications you will need to know for the prescription writing questions include: • Amoxicillin : Adults: 750-1750 mg total daily dosage given PO every 8 hrs Children: 20-90 mg/kg total daily dosage given PO every 8 hrs • Tetracycline : Adults: 1000-2000 mg total daily dosage given PO every 6 hrs Children: 25-50 mg/kg total daily dosage given PO every 6 hrs • Benzoyl Peroxide Cream : 10% cream: thin film applied topically once daily initially; increase to 2-3x/day PRN • Acyclovir : Capsule: 200 mg/Tablet: 400 & 800 mg/Suspension: 200 mg/5 mL Orolabial HSV: 200 mg 5x/day OR 400 mg TID x 7-10 days Orolabial HSV in ICH: 400 mg TID x 5-10 days or until lesions have healed Varicella in children under 40 kg: 20 mg/kg per dose QID x 5 days Varicella in children over 40 kg & adults: 800 mg QID x 5 days Herpes zoster: 800 mg 5x/day x 7-10 days • Timolol ophthalmic : 0.25% solution: 1 drop daily-BID 0.5% solution: 1 drop daily-BID 0.25% gel: 1 drop daily 0.5% gel: 1 drop daily • Betaxolol : 0.25% suspension: 1 drop BID