NR 568/ NR568 Midterm Exam – Advanced Pharmacology for AGPCNP 2026/2027 | Chamberlain | Latest Questions & Verified Answers

NR 568/ NR568 Midterm Exam – Advanced Pharmacology for AGPCNP 2026/2027 | Chamberlain | Latest Questions & Verified Answers Classification of Antimicrobial Drugs • There are two main classification schemes 1. Classification by Susceptible Organism Antibacterial Drugs • Narrow Spectrum-Gram+ cocci/bacilli, Gram- aerobes, M. tuberculosis • Broad Spectrum-Gram+ cocci and gram- bacilli Antiviral Drugs • Drugs for HIV infection • Drugs for influenza • Other antiviral drugs-acycolvir Antifungal Drugs-amphotericin B; Azoles 2. Classification by Mechanism of Action • Inhibitors of cell wall synthesis • Drugs that disrupt the cell membrane • Bactericidal inhibitors of protein synthesis • Bacteriostatic inhibitors of protein synthesis • Drugs that interfere with synthesis or integrity of bacterial DNA and RNA • Antimetabolites • Drugs that suppress viral replication List the 10 classes of Antibiotics name examples HINT (acronym): Abx Can Terminate Protein Synthesis For Microbial Cells Like Germs ● Aminoglycosides-gentamicin, streptomycin ● Cephalosporins-Cephalexin (Keflex) ● Tetracyclines-tetra/doxyclycline ● Penicillins-PCN G/V, amoxicillin ● Sulfonamides-trimethoprim/sulfamethoxazole ● Fluoroquinolones-ciprofloxacin ● Macrolides-erythromycin, Azithromycin ● Carbapenems-imipenem, meropenem ● Lincosamides-Clindamycin ● Glycopeptides-Vancomycin Other ways to organize classes of Drugs What is Beta Lactams? • they have a β-lactam ring in their structure, the penicillins are known as β-lactam antibiotic • The β-lactam family also includes the cephalosporins, carbapenems, and aztreonam • All of the β-lactam antibiotics share the same mechanism of action: disruption of the bacterial cell wall • they are bactericidal; bacteria must be actively growing for them to work Other ways to organize classes of Drugs - Bacteriostatic Inhibitors of Protein Synthesis include 1. Tetracycline 2. Macrolide 3. Clindamycin Other ways to organize classes of Drugs - Bactericidal antibiotics directly kill bacteria and include aminoglycosides, beta-lactams, fluoroquinolones, metronidazole, most antimycobacterial agents, streptogramins, vancomycin. Other ways to organize classes of Drugs What are Antimetabolites? Sulfonamides, Trimethoprim & Nitrofurantoin Broad spectrum vs narrow spectrum Broad-spectrum - Broad-spectrum penicillins: ampicillin and others - Extended-spectrum penicillins: piperacillin and others - Cephalosporins (third generation) - Tetracyclines: tetracycline and others - Carbapenems: imipenem and others - Trimethoprim - Sulfonamides: sulfisoxazole and others - Fluoroquinolones: ciprofloxacin and others narrow-spectrum - Penicillin G and V - Penicillinase-resistant penicillins: oxacillin and nafcillin - Vancomycin - Erythromycin - Clindamycin - Aminoglycosides: gentamicin and others - Cephalosporins (first and second generations) - Isoniazid - Rifampin - Ethambutol - Pyrazinamide - Understand broad spectrum vs narrow spectrum agents Broad-Spectrum: 1. Targets wider number of bacteria types. Acts on both 2. Commonly used against 3. Commonly used for (blank) therapy; when the pathogen is unknown or 4. A major con is disruption of Narrow-Spectrum: 1. Effective against a specific 2. Used when infecting pathogens Broad-Spectrum: 1. gram- and gram + organisms 2. H. influenzae, E. coli, Proteus mirabilis, enterococci, N. gonorrhoeae 3. empiric; infection with multiple types of bacteria is suspected. 4. native bacteria and the development of antimicrobial resistance Narrow-Spectrum: 1. bacteria type 2. is known - Understand empiric treatment and when to use: 1. It is used when 2. is initiated based on two main things: 3. Can be used in severe illnesses when 4. What is the protocol for these pts 5. IV vs. PO? 6. Bactericidal vs. Bacteriostatic 1. when cultures are not available or results are not back yet 2a. NP's knowledge of the patient's history, typical pathogens, gram stain results, and 2b. local susceptibility reports on which abx work best in certain geographic locations. 3. Critically ill pts need immediate empiric antibiotics 4. after first set of cultures is obtained, do not wait for results. Give empiric (broad-spectrum) abx 5. IV-for Critical or severe infections PO for Mild/moderate or pts; Switch from IV to PO once the patient is stable 6. Bactericidal antibiotics directly kill bacteria preferred for immunocompromised patients such as those with diabetes, HIV, cancer or overwhelming infections What types of infections are usually viral and do not warrant antibacterial agents? community-acquired, mostly viral, upper respiratory tract infections; - these infections are usually viral patients are exposed to all the risks of abx but have no chance of receiving benefits Penicillins-Examples 1. Narrow-spectrum PCNs (penicillinase sensitive) 2. Narrow-spectrum penicillins: (penicillinase-resistant) 3. Broad-spectrum penicillins (aminopenicillins) 4. Extended-Spectrum Penicillins (Antipseudomonal Penicillins) 1. Penicillin G, Penicillin V 2. Nafcillin, Oxacillin, Dicloxacillin 3. Ampicillin, Amoxicillin 4. piperacillin Indications for use of PCNs 1. Penicillin G, Penicillin V (Narrow/PCN-ase S) 2. Nafcillin, Oxacillin, Dicloxacillin (Narrow/PCN-ase R) 3. Ampicillin, Amoxicillin (Broad) 4. piperacillin (extended) 1. streptococcal pharyngitis, N. Meningitis/gonorrhoeae; active against most gram +/- cocci and spirochetes-T. pallidum 2. use for all PCN-ase R Staph infections ie: S. aureus and S. epidermidis, NOT MRSA 3. Amoxicillin-1st line for ENT/Skin/UTIs ie: AOM and sinusitis, Amoxicillin + clavulanate first line for Severe AOM & animal/human bites, Ampicillin-1st line for infants with UTIs 4. used mainly for P. aeruginosa; often combined with β-lactamase inhibitor (Zosyn), also used for H. influenzae, E. coli, enterococci, N. gonorrhoeae, MOA for PCNs • disruption of the bacterial cell wall • they are bactericidal; bacteria must be actively growing for them to work Contraindications and high-risk patients of PCNs 1. What is the main contraindication in general? 2. Penicillin G, Penicillin V 3. Ampicillin, Amoxicillin (Broad) 4. piperacillin (extended) 1. PCN allergy- it can range from a minor rash to anaphylaxis; it can decrease over time but if severe should NOT be used; if no other alternative pts can undergo skin testing but this still carries a risk 2. The next most common ADR is non-allergic rash; Probenecid (antigout med) prolongs the half-life of PCNs and increases risk for toxicity 3. rash and diarrhea are most common 4. can cause bleeding by disrupting plt function • Dosage should be reduced in patients with renal impairment Monitoring needs for PCNs 1. Monitoring for renal impairment which can cause 2. Identifying High-Risk Patients 3. Baseline data 1. PCNs to accumulate to toxic levels. Also monitor for allergy symptoms, C.diff diarrhea 2. Penicillins should NOT be used in patients with a history of severe allergic reactions to penicillins, cephalosporins, or carbapenems 3. Obtain a culture Patient-Centered Care Across the Life Span-Penicillins Infants • Penicillins are used safely in infants with Children/adolescents • Penicillins are a common drug used to treat Pregnant women • Although there are no well-controlled studies in pregnant women Breastfeeding women • (blank) is safe for use in breastfeeding mothers. Older adults • Doses should be adjusted in older adults with Infants • bacterial infections, including syphilis, meningitis, and group A streptococcus. Children/adolescents • bacterial infections in children. Pregnant women • evidence we do have suggests there is no second or third trimester fetal risk. Breastfeeding women • Amoxicillin; Data are lacking regarding transmission of some other penicillins from mother to infant through breast milk. Older adults • renal dysfunction. Patient Education-in general 1. Finishing the Prescribed Course It is imperative that antibiotics not be discontinued prematurely. Early discontinuation is a common cause of recurrent infection, and the organisms responsible for relapse are likely to be more drug resistant than those present when treatment began Alternative drugs to patients with a history of penicillin allergy • If the allergy is mild, a cephalosporin is often an appropriate alternative • For many infections, vancomycin, erythromycin, and clindamycin are effective and safe alternatives Contraindications and high-risk patients Cephalosporins 1. the Main risk with cephalosporins is 2. Cephalosporins have been reported with type I allergic reactions 3. Contraindicated for 4. Caution is needed if these drugs are combined with other bleeding agents 1. C. difficile infection 2. serum sickness-like reactions, and other skin rashes, arthralgia, and fever 3. pts with severe PCN allergy or Ceph allergy 4. (anticoags, NSAIDS, thrombolytic) they can interfere with Vit K Indications for use of Cephalosporins 1. First-generation-Cephalexin (Keflex) 2. Second generation-cefoxitin (Mefoxin) 3. Third-generation cefotaxime 4. Fourth generation cefepime (Maxipime) 5. ceftaroline (Teflaro) 1. narrow spectrum, skin, soft tissue infections, used for Gram + S. Aureus/epidermidis/streptococci, used as an alternative in pts with a mild PCN allergy, surgical prophylaxis 2. broader spectrum, otitis, sinusitis, respiratory tract, Klebsiella, E. coli Gr+ /Gr- 3. more resistant to β-lactamases; meningitis, gram - nosocomial infections 4. narrow spectrum-HAP and resistant pseudomonas 5. narrow spectrum; MRSA infections Cephalosporins MOA - disrupt cell wall synthesis - are bactericidal, often resistant to β-lactamases Monitoring needs for Cephalosporins 1. In patients with renal insufficiency, 2. Baseline Data: Take samples Patient Education 3. Instruct patients to report increase in 4. cefazolin-1st gen and cefotetan—2nd gen; can induce a state of alcohol intolerance 1. dosages of most cephalosporins must be reduced 2. for culture to determine the identity and sensitivity Patient Education 3. stool frequency; All cephalosporins can promote C. difficile infection. 4. the disulfiram effect can be very dangerous pts taking these drgs should avoid alcohol Lifespan considerations for Cephalosporins - see notecard 28 Indications for use Carbapenems 1. imipenem is the most effective beta-lactam 2. Mechanism of Action 1. for anaerobic bacteria & serious infections caused by gram-pos/neg cocci, gram-neg bacilli (broad spect) 2. Imipenem binds to two PBPs, causing weakening of the bacterial cell wall; resistant to all beta-lactamases Contraindications and high-risk patients Carbapenems 1. Imipenem can reduce blood levels of 2. Dosage should be reduced in patients 1. valproate, an anti-seizures med; the combo should be avoided 2. with renal impairment 1. Monitoring Carbapenems 2. Baseline Data: 1. No routine laboratory monitoring is suggested. 2. Take samples for culture to determine the identity and sensitivity of the infecting organism. Patient-Centered Care Across the Life Span Cephalosporins, Carbapenems, and Others Infants • Third-generation cephalosporins are used to Children/adolescents • Cephalosporins are commonly used to treat Pregnant women • (blank) carries a black box warning Breastfeeding women • (blank) are generally not expected to cause adverse effects in breastfed infants. Older adults • Doses should be adjusted in older adults with Infants • treat bacterial infections in neonates as well as infants. Children/adolescents • bacterial infections in children, including otitis media and gonococcal and pneumococcal infections. Pregnant women • Televancin (Glycopeptide); secondary to risk for adverse developmental outcomes. All cephalosporins appear safe for use in pregnancy. Breastfeeding women • Cephalosporins Older adults • decreased renal function. Other Inhibitors of Cell Wall Synthesis Aztreonam Indications for use Vancomycin-Glycopeptide 1. Principal indications are 2. MOA 3. indications for using Telavancin (Glycopeptide) 1. C. difficile infection, MRSA infection, or allergy to PCN 2. vancomycin inhibits cell wall synthesis 3. treating vancomycin-resistant infections; Contraindications and high-risk patients Vancomycin-Glycopeptide 1. In patients with 2. Black Box Warning of Telavancin (Glycopeptide) 1. renal impairment, dosage must be reduced 2. when used to tx HAP/VAP in patients with a Cr clearance of less than 50 mL/min has been associated with increased mortality • can prolong the QT intervals • Contraindicated in pregnancy Monitoring needs for Vancomycin-Glycopeptide 1. Baseline Data: 2. Monitoring: Vancomycin (blank) should be monitored during IV administration. 1. Take samples for culture to determine the identity and sensitivity of the infecting organism. 2. drug levels Indications for use Tetracyclines 1. broad-spectrum abx with a variety of uses 1. rickettsial diseases, 2. Chlamydia trachomatis infections, (3) brucellosis; (4) cholera; (5) pneumonia caused by Mycoplasma pneumoniae; (6) Lyme disease; (7) anthrax; (8) gastric infection with H. pylori 9. severe acne vulgaris MOA for Tetracyclines tetracyclines suppress bacterial growth by inhibiting protein synthesis by binding to the 30S ribosomal subunit and thereby interfering with the messenger RNA–ribosome complex. Contraindications and high-risk patients for Tetracyclines 1. Tetracyclines bind to calcium in developing teeth, 2. Hepatotoxicity-Tetracyclines can cause fatty infiltration of 3. Renal Toxicity-tetracycline and demeclocycline are 4. Drug and Food Interactions 1. causing staining of teeth of the infant; Discoloration of permanent teeth occurs when taken by children aged 4 months to 8 years; avoid in children 8 yrs 2. the liver; highest risk-Pregnant and postpartum 3. contraindicated in pts with renal impairment; doxycycline or minocycline are safe with renal impairment as they're eliminated by liver 4. Can bind with certain metal ions (calcium, iron, magnesium, aluminum, zinc) found in milk products, calcium/iron supplements, magnesium-containing laxatives, and most antacids resulting in decreased absorption Patient Education for Tetracyclines 1. Sun Exposure Risk With Tetracyclines- 1. All tetracyclines can increase the sensitivity of the skin to UV light resulting in sunburn. Advise patients to avoid prolonged exposure to sunlight, to wear protective clothing, and to apply sunscreen to exposed skin Patient-Centered Care Across the Life Span-Tetracyclines Children/adolescents • Tetracyclines should not be used in children younger than Pregnant women • Animal studies reveal that tetracyclines can cause Breastfeeding women • Use of tetracyclines during tooth development can cause Older adults • Tetracyclines can interact with drugs, including Children/adolescents • 8 years because they may cause permanent discoloration of the teeth. Pregnant women • fetal harm in pregnancy. Thus this class of drugs should be avoided in pregnant women. Breastfeeding women • permanent staining. Tetracyclines should be avoided by breastfeeding women. Older adults • digoxin. & many medications, check for interactions. Indications for use Macrolides 1. erythromycin is the treatment of choice 2. may be used as an alternative to 3. macrolides are all considered first-line treatments 4. Like are also tetracyclines are DOC for 1. for acute diphtheria & Bordetella pertussis 2. PCNs in pts w/allergy 3. for patients with CAP who have no comorbidities or risk factors for drug-resistant pathogens 4. certain chlamydial infections (urethritis, cervicitis) Mechanism of Action Macrolides Protein synthesis inhibition: erythromycin binds to the 50S ribosomal subunit • The drug is usually bacteriostatic but can be bactericidal against highly susceptible organisms or when present in high concentrations Contraindications and high-risk patients Macrolides 1. When erythromycin is combined with a CYP3A4 inhibitors (ie: verapamil, diltiazem, azole antifungals-ketoconazole, HIV protease inhibitors (e.g., ritonavir, saquinavir) 2. erythromycin should be avoided by patients with 3. food decreases absorption of all except erythromycin 4. As a CYP3A4 inhibitor erythromycin can raise levels of 1. there is 5x the risk for sudden cardiac death 2. congenital QT prolongation and by those taking class IA or III antidysrhythmic drugs 3. ethylsuccinate or enteric-coated formulations 4. theophylline, carbamazepine (used for szs and bipolar disorder), and warfarin Monitoring needs Macrolides 1. There is no Patient education 2. GI disturbances (epigastric pain, nausea, vomiting, diarrhea) are the most common side effects; These can be reduced by 1. baseline or routine monitoring required 2. administering with meals but should only be with acid stable formulations-enteric-coated Lifespan considerations Macrolides Indications for use Clindamycin-Lincosamides 1. DOC for severe group A 2. widely as an alternative 1. streptococcal infection and for gas gangrene & anaerobic infections outside the CNS 2. to penicillin b/c its effective against gram + cocci MOA for Clindamycin - Clindamycin is usually bacteriostatic • Clindamycin binds to the 50S subunit of bacterial ribosomes and thereby inhibits protein synthesis Contraindications and high-risk patients Clindamycin-Lincosamides 1. Black Box Warning: Clindamycin can cause potentially fatal 1. C. difficile assoc diarrhea (CDAD)- characterized by profuse, watery diarrhea (10 to 20 watery stools per day) 1. Monitoring needs for Clindamycin-Lincosamides 2. Patient education 1. Monitor for CDAD 2. Patients should promptly report any diarrhea to their health care provider. Indications for use Aminoglycosides ie gentamicin, tobramycin 1. Parenteral Therapy: tx of serious infections 2. Topical Therapy: is used for 3. Often given in Combination therapy with drugs that 1. from aerobic gram-neg bacilli ie: E. coli, Klebsiella pneumoniae, Serratia marcescens, Proteus mirabilis, and P. aeruginosa-common in Cystic Fibrosis 2. Gentamicin and tobramycin can treat eye infections, neomycin is for infections of ear and eye 3. weaken the cell wall-PCNs, cephs, Vanc Mechanism of Action for Aminoglycosides • these drugs bind to the 30S ribosomal subunit, causing inhibition & termination of protein synthesis, & production of abnormal proteins which is why they are bactericidal & NOT bacteriostatic Contraindications and high-risk patients Aminoglycoside 1. • Black Box Warning: All aminoglycosides can accumulate within the inner ears, causing 2. Black Box Warning: Neurotoxicity: sx may include 3. Black Box Warning: (blank) has highest risk increases in pts w/ prolonged use and with preexisting renal impairment; 3. These drugs readily cross the placenta and may be 1. irreversible injury ototoxicity that can impair both hearing and balance 2. numbness, tingling, muscle twitching, and seizures 3. Nephrotoxicity; injury to the kidneys usually reverses after aminoglycoside use is stopped; risk increased when pts are on loop diuretics, other nephrotoxic drugs and with prolonged used of aminoglycosides. 4. toxic to the fetus Monitoring needs for Aminoglycosides 1. Baseline Data 2. Monitoring: 3. Provider monitoring 1. Blood and/or urine cultures. 2. Aminoglycoside levels (peaks-to have sufficient killl levels, and troughs-to prevent ototoxicity) and renal function must be monitored. 3. The first sign of impending cochlear damage (tinnitus, persistent headache, or both). Patient Education for Aminoglycosides 1. hearing loss begins 2. • The first sign of impending vestibular damage is 3. Pts should be informed about the 1. in the high-frequency range then progresses to Loss of low-frequency headache, which may last for 1 or 2 days; After that, nausea, unsteadiness, dizziness, and vertigo begin to appear. 3. sx of vestibular and cochlear damage and instructed to report them Patient-Centered Care Across the Life Span-Aminoglycosides Infants • Aminoglycosides are approved to treat bacterial infections in infants younger than Children/adolescents • Aminoglycosides are Pregnant women • There is evidence that use of aminoglycosides in pregnancy can Breastfeeding women • (blank) is probably safe to use during lactation Older adults • Caution must be used regarding decreased Infants • 8 days. Dosing is based on weight and length of gestation. Children/adolescents • safe for use against bacterial infections in children and adolescents. Pregnant women • harm the fetus. Breastfeeding women • Gentamicin; although there is limited information Older adults • renal function in the older adult. Indications for use Sulfonamides and trimethoprim combo is abbreviated SMZ/TMP 1. 1st line drug for Uncomplicated UTIs 2. sulfonamides are alternatives to pt's with allergies to 3. Topical sulfonamides are used to tx infections 4. TMP/SMZ is valuable for 1. Trimethoprim/sulfamethoxazole 3 days -OR- Nitrofurantoin 5 days 2. PCN, doxycycline & erythromycin 3. of the eyes and to suppress bacteria in burn patients and bacterial vaginosis caused by G. vaginalis 4. UTIs, otitis media, bronchitis MOA for Sulfonamides/Trimethoprim Sulfonamides suppress bacterial growth by inhibiting key precursors of folate; Remember* all organisms depend on folate for DNA, RNA, and protein synthesis • Selective toxicity: it doesn't harm humans b/c mammalian cells can take up folate from their diet whereas bacteria must synthesize it from precursors Contraindications and high-risk patients Sulfonamides and trimethoprim 1. Hypersensitivity Reactions; are frequent with 2. Can cause Hematologic: blood dyscrasias including 3. Sulfonamides promote (blank) in newborns by displacing bilirubin from plasma proteins 4. Because older sulfas can form crystalline aggregates they are contraindicated in 4. trimethoprim should be avoided in pts with folate deficiency such 5. Trimethoprim suppresses renal excretion of potassium and can 6. SMZs can intensify the effects of 1. topical sulfas and include: Mild reactions—rash, drug fever, photosensitivity to Severe reaction- Stevens-Johnson syndrome; d/c use if a rash is observed 2. including hemolytic anemia in patients with G6PD deficiency, agranulocytosis, leukopenia, thrombocytopenia, & bone marrow suppression 3. kernicterus 4. patients with severe renal disease and req reduced dosage for pts with renal impairment 5. as ETOH abuse and in pregnant women 6. promote hyperkalemia; Risks are elevated in those with renal impairment, & those taking drugs that elevate K+, including ACEIs, ARBs, aldosterone antagonists 7. warfarin, phenytoin, and sulfonylureas Monitoring needs for Sulfonamides and trimethoprim 1. Monitoring for Sulfonamides 2. Monitoring for trimethoprim 3. Monitoring for both 4. Baseline Data: Establish infection: 1. Monitor renal fx for sulfas; In pts with renal impairment (Cr clearance-15–30 mL/min), dosage should be decreased by 50% 2. If hyperkalemia is suspected due to trimethoprim, K must be checked 4 days after starting treatment. 3. CBC should be monitored if the patient develops S/S of blood disorders, as should CD4+ count for patients with HIV infection; S/S of hypersensitivity reactions 4. UA (if UTI is suspected) with C&S as indicated. Obtain CBC with diff if indicated or if treatment will be prolonged. Renal function should be checked if there is concern that it may be compromised. Patient Education-Sulfonamides 1. Encourage hydration; pts should drink at least 2. To prevent photosensitivity reactions, advise patients 3. Pts should be instructed to observe for alterations that may indicate 1. 8-10 glasses of water/noncaffeinated fluids per day to decrease the risk for crystalluria. 2. to avoid prolonged exposure to sunlight, wear protective clothing, apply sunscreen, avoid tanning beds 3. hypersensitivity (esp with topical agents) (e.g., rash) and to report these promptly if they occur. Lifespan considerations for Sulfonamides and trimethoprim Infants • Use of sulfonamides in infants younger than 2 months Pregnant women • Systemic sulfonamides & trimethoprim may cause birth defects if taken during Breastfeeding women • Sulfonamides are secreted in breast milk. Women should be warned that Older adults • Older patients are more likely to Infants • can cause kernicterus, a potentially fatal condition. Pregnant women • the first semester. If taken near term, the infant may develop kernicterus; trimethoprim may impact folate levels Breastfeeding women • breastfeeding an infant younger than 2 months can cause kernicterus Older adults • adverse effects, and when experienced, the effects are more likely to be severe. Life-threatening effects—including neutropenia, Stevens-Johnson syndrome, and toxic epidermal necrolysis— occur more frequently in older adults. Indications for use Nitrofurantoin 1. Nitrofurantoin is indicated for acute infections of the 2. can also be used for prophylaxis of 3. Can used used as an alternative for a 1. lower urinary tract (uncomplicated cystitis) NOT the upper urinary tract 2. recurrent lower UTI (called urinary antiseptics) 3. Sulfa allergy Nitrofurantoin Mechanism of Action • is a broad-spectrum antibacterial drug • produces bacteriostatic effects at low concentrations and bactericidal effects at high concentrations • Nitrofurantoin injures bacteria by damaging DNA Another Urinary AntiSeptic: Methenamine Mechanism of Action • Methenamine is a prodrug that, under acidic conditions (pH 5.5), breaks down into ammonia and formaldehyde • formaldehyde denatures bacterial proteins, causing cell death Contraindications and high-risk patients for Nitrofurantoin 1. Pulmonary: can induce serious pulmonary reactions: 2. Can cause hematologic reactions: 3. Can cause Peripheral neuropathy: may be irreversible; highest risk in pts with 4. Do NOT use nitrofurantoin in pts with 5. Hepatotoxicity: has caused severe liver injury, 6. Birth defects: should absolutely be avoided in pregnant 1. Most common-manifest as dyspnea, chest pain, cough-stop drug if these sx are observed 2. agranulocytosis, leukopenia, thrombocytopenia, and megaloblastic anemia; Avoid in newborns 1 mo, pregnant women near term, pts with G6PD deficiency 3. renal impairment taking nitrofurantoin chronically 4. renal impairment 5. Deaths have occurred. Patients should undergo periodic tests of liver function 6. women near term: 38–42 weeks of gestation Monitoring needs for Nitrofurantoin 1. Routine monitoring: None was listed in book but should undergo 2. Baseline Data 1. renal and liver fxn tests for in pts w/ liver impairment 2. Renal function, urinalysis with culture Patient education for Nitrofurantoin 1. most adverse reactions are GI (anorexia, nausea, vomiting, diarrhea). These can be minimized by 2. Early symptoms of Peripheral neuropathy include: 3. Detecting acute pulmonary injury: 4. Inform pregnant women about risk birth defects and to avoid use 5. Severe liver damage may manifest as 1. administering nitrofurantoin with milk or with meals, 2. muscle weakness, tingling sensations, and numbness. Patients should report them immediately 3. Instruct pts to report: dyspnea, chest pain, chills, fever, cough; if present stop tx 4. especially in 3rd trimester 5. as hepatitis, cholestatic jaundice, and hepatic necrosis Patient-Centered Care Across the Life Span-Drugs for UTI: Nitrofurantoin, Methenamine & Fluoroquinolones Infants • (blank & blank) are recommended to treat infants with UTI. Children/adolescents • Methenamine hippurate is approved for use in children between Pregnant women • UTIs in pregnancy must be treated as Breastfeeding women • Fluoroquinolones have been Older adults • Nitrofurantoin should be Infants • Ampicillin and gentamycin; Nitrofurantoin is contraindicated in infants less than one month of age. Trimethoprim/sulfamethoxazole should also be avoided in the early stages of infancy. Children/adolescents • 6-12 years of age. Methanamine mandelate can be used in children 6 years of age. Pregnant women • complicated infections. Nitrofurantoin is contraindicated in the third trimester of pregnancy. Fluoroquinolones should also be avoided in pregnancy. Breastfeeding women • detected in breast milk at low doses. Short-term use during breastfeeding is acceptable. For greatest safety, breastfeeding should be avoided between 4 and 6 hours after a dose. Older adults • avoided in older adults with decreased renal function. Indications for use Fluoroquinolones ie: Cipro, ofloxacin (Floxin), levofloxacin (Levaquin) and moxifloxacin 1. approved for a variety of infections including 2. For CAP they should only be used if 3. What are preferred agents for complicated UTIs & Pyelonephritis 4. Also used as 1st line therapy for 4. This is DOC for prevention of 5. Two approved used in children 1. the respiratory tract, urinary tract, (GI) tract, bones, joints, skin, and soft tissues 2. individual has been treated with an antimicrobial agent in the last 90 days that could increase the risk of a drug-resistant microbe 3. Ciprofloxacin, levofloxacin 4. acute prostatitis 4. anthrax 5. (1) complicated UTIs/kidney infections-E. coli, (2) postexposure prophylaxis of anthrax MOA of Fluoroquinolones Benefits derive from disrupting DNA replication/cell division; Fluoroquinolones DO NOT disrupt synthesis of proteins or the cell wall • fluoroquinolones are broad-spectrum agents; Contraindications and high-risk patients of Fluoroquinolones 1. Older adults are at high risk for (HINT two things) 2. Others at high risk for tendon rupture include 3. Black Box Warning: Ciprofloxacin and other fluoroquinolones can 4. These broad spectrum abx can also cause infections such as 5. Like tetracylcines Absorption can be reduced by 6. Ciprofloxacin can increase plasma levels of 1. for confusion, somnolence, psychosis, and visual disturbances; cartilage damage(tendon rupture), usually of the Achilles tendon highest risk are those 60 years, 2. those taking glucocorticoids, those with a heart, lung, or kidney transplantation 3. exacerbate muscle weakness in patients with myasthenia gravis-avoid in these pts 4. Candida infections of the pharynx and vagina may develop and C. Diff during treatment 5. compounds that have aluminum/magnesium-containing antacids, iron salts, zinc salts, sucralfate, calcium supplements, and milk and dairy 6. theophylline, warfarin, and tinidazole (an antifungal) Patient Education with Fluoroquinolones 1. fluoroquinolones should be discontinued at the first 2. fluoroquinolones pose a risk for phototoxicity 1. sign of tendon pain, swelling, or inflammation• In addition, patients should refrain from exercise until tendinitis has been ruled out 2. (severe sunburn), characterized by burning, erythema, blistering, and edema. • This can occur even if sunscreen has been applied.• • Drug should be withdrawn at the first sign of a phototoxic reaction (e.g., burning sensation, redness, rash) Monitoring needs with Fluoroquinolones 1. Although no routine or baseline 1. monitoring is listed in book; Levofloxacin needs reduction if GFR is 50ml/min Patient-Centered Care Across the Life Span-Fluoroquinolones Children/adolescents • (blank & blank) are the only Pregnancy • Although data reveal little potential for fluoroquinolone toxicity in the fetus, Breastfeeding women • Effects of fluoroquinolones on the nursing infant are largely Older adults • Fluoroquinolones are generally well tolerated in older adults. Children/adolescents • Ciprofloxacin and levofloxacin; fluoros approved for use in children. Because of concerns of tendon injury, fluoros are generally avoided in this population. Pregnancy • flouros are generally avoided Breastfeeding women • unknown. Other medications should be considered if possible. Older adults • For safe dosing, creatinine clearance should be calculated Miscellaneous Abx-Metronidazole 1. MOA 2. Clinical uses 3. Adverse effects 1. interacts with DNA to cause strand breakage of structure, inhibition of synthesis and cell death 2. used in combo with a tetracycline and bismuth subsalicylate to eradicate H. pylori in PUD; used as an alternative to vanc in tx of C. difficile infection 3. Black Box Warning: has been assoc with increased carcinogenic risk in mice and rats Patient-Centered Care Across the Life Span-Antimicrobials 1. Infants Infants are highly vulnerable to drug toxicity. Because of 2. Children/adolescents The tetracyclines are toxic b/c 3. Pregnant women Antimicrobial drugs can cross the 4. Breastfeeding women Antibiotics can enter breast milk, possibly affecting the 5. In the older adult, heightened drug sensitivity is due in large part 1. Infants • poorly developed kidney and liver function, neonates eliminate drugs slowly. Use of sulfonamides in newborns can produce kernicterus, a severe neurologic disorder caused by displacement of bilirubin from plasma proteins . 2. Children/adolescents • They bind to developing teeth, causing discoloration. 3. Pregnant women • placenta, posing a risk to the developing fetus. For example, when gentamicin is used during pregnancy, irreversible hearing loss in the infant may result. 4. Breastfeeding women • the nursing infant. ie, sulfonamides can reach levels in milk that are sufficient to cause kernicterus As a general guideline, benefits should outweigh the risks. 5. Older adults • to reduced rates of drug metabolism and drug excretion, which can result in accumulation of antibiotics to toxic levels. What drugs are considered safe during pregnancy? PCNs, cephalosporins & erythromycin If someone is allergic to one antibiotic group, which do you prescribe in its place? 1. If the PCN allergy is mild, a 2. If the PCN allergy is severe, 3. If a pt has a Sulfa allergy what do you prescribe? 1. a cephalosporin is often an appropriate alternative 2. vancomycin, erythromycin, and clindamycin are effective and safe alternatives; AVOID carbapenems 3. Nitrofurantoin Which antibiotics require renal dose adjustments? Agents to avoid in severe Chronic Kidney Disease - Penicillin G (Myoclonus, Seizures, coma risk) - Imipenem (Seizure risk); Meropenem safe - Tetracycline (Uremia); Doxycycline safe - Nitrofurantoin (peripheral neurotoxicity) - Aminoglycosides (close monitoring if used) Which antibiotics require renal dose adjustments? Agents that must be reduced in renal impairment Penicillins Cephalosporins Penicillins - Penicillin Reduce to 50% if GFR 30 ml/min - Amoxicillin GFR10 ml/min - Augmentin Reduce if GFR30 ml/min Cephalosporins - Cefazolin GFR 50 ml/min; Reduce to 50% if GFR10 - Cefuroxime - Cephalexin Which antibiotics require renal dose adjustments? Agents that must be reduced in renal impairment Fluoroquinolones Macrolides Antimetabolites Glycopeptides Fluoroquinolones - Ciprofloxacin Reduce to 50-75% if GFR50 ml/min - Levofloxacin Reduce if GFR50 ml/min; Avoid if GFR10 ml/min Macrolides - Clarithromycin Reduce by 50% if GFR30 ml/min Antimetabolites - TMP-SMZ,( Bactrim) Reduce to 50% if GFR 30 ml/min Avoid if GFR15 ml/min Glycopeptides - Vancomycin Adjust based on drug level&Cr Clearance Antibiotics that require NO renal dose adjustment Azithromycin-macrolide Ceftriaxone-Ceph 3rd gen Clindamycin-Lincosamides Doxycyline-tetra Linezolid Moxifloxacin-fouro Nafcillin Rifampin Clostridiodies difficile Infection-another section • Causes/Transmission Causes/Transmission • CDI is almost always preceded by the use of abx, which kill off normal gut flora and allow C. diff. to flourish. • Antibiotics most likely to promote CDI are clindamycin, second- and third-generation cephalosporins, and fluoroquinolones Treatment of C. Diff 1. Initial episode: mild or moderate 2. Initial episode: fulminant-characterized by shock, megacolon, or hypotension— 3. Alternative tx 1. oral vancomycin or fidaxomicin-a narrow spectrum macrolide 2. oral vancomycin is preferred. 3. Metronidazole can be used in situations where oral vancomycin or fidaxomicin is not available Community-Acquired Pneumonia (CAP) - pneumonia acquired outside hospital or healthcare facilities - most often seen in primary care. Causative agents 1. Most common bacteria is 2. What other pathogens can cause CAP in the General population 3. What causes CAP in Smokers and those with COPD 4. What causes CAP in those with cystic fibrosis (CF) 5. What is the Gold Standard for CAP dx 6. What pathogen is usually transmitted by inhaling mist or aspiration liquid that comes from a water source 1. Streptococcus Pneumoniae (aka pneumococcus); gram positive; also most deadly 2. Atypical bacteria (Mycoplasma pneumoniae)-often seen in people of close proximity (correctional facilities, college dormitories, SNFs) or Viruses (influenza, RSV) 3. Haemophilus influenzae (gram-neg) 4. Pseudomonas aeruginosa (gram neg) 5. Chest x-ray 6. Legionella sp Community-Acquired Pneumonia (CAP) Treatment options for Typical pneumonia 1. If pt has NO comorbidities: 2. What other class can be used for penicillin-sensitive S. pneumoniae 3. If those therapies FAIL and a resistant organism is suspected 1. First-line agents: Beta-lactam or doxycycline ○ Amoxicillin 1,000 mg PO TID x 5-7 days OR ○ Doxycycline 100mg PO BID x 5-7 days ● Alternative: Macrolides ○ Azithromycin (Z-pack) daily x 5 days ○ Clarithromycin 2. Linezolid (Zyvox) 3. the use of respiratory fluoroquinolones active against S. pneumoniae is warranted Community-Acquired Pneumonia (CAP) Treatment options for Atypical Pneumonia 1. What is the 1st DOC cause by Mycobacterium Pneumoniae 1. Macrolide-Erythromycin Community-Acquired Pneumonia (CAP) Treatment options 1. If pt HAS comorbidities: ETOH; CHF; heart/lung/liver/kidney disease; abx in the last three months; diabetes; splenectomy/asplenia or high rates (25%) of macrolide-resistant S. pneumoniae 2. What other drug class can be used for high Antimicrobial Resistance 1. Combination therapy (beta-lactam + macrolide) ○ Amoxicillin/clavulanate (Augmentin) 1,000mg/62.5mg PO BID -or- Cephalosporin cefpodoxime or Ceph-cefuroxime + azithromycin (Z-pack) or clarithromycin 2. Respiratory fluoroquinolone; duration 5-7 days ○ Moxifloxacin ○ Gemifloxacin - Treatment of chlamydial pneumonia: 1. C. pneumoniae (atypical pneumonia) is more commonly seen in 2. 1st line Treatment is 1. children and young adults 2a. Macrolides Azithromycin (5 days total) 2b. Tetracycline - 250 mg orally every 6 hours for 14-21 days 2c. Doxycyclines for 10 days - Do not use doxy in pregnant women 2d. Fluoroquinolones-Levofloxacin for 7-14 days Week 2-Fungal Fungal infections - Mycoses (fungal infections) can be categorized as either systemic or superficial. - Understanding the appropriate drug choice for each type of fungal infection is an essential element of safe prescribing 1. Systemic mycoses can be subdivided into two categories: 2. The opportunistic mycoses include— 3. nonopportunistic infections include . Treating systemic mycoses can be difficult; may require prolonged therapy with drugs that frequently prove toxic. 1. opportunistic infections and nonopportunistic infections. 2. candidiasis, aspergillosis, cryptococcosis, and mucormycosis—are seen primarily in debilitated or immunocompromised hosts 3. sporotrichosis, blastomycosis, histoplasmosis, and coccidioidomycosis; can occur in any host & are relatively uncommon Treatment Overview - List drugs for systemic infections - List drugs for superficial (local infections) Clotrimazole is not active against onychomycosis (nail fungus) Fluconazole [Diflucan] is active against all three Treatment for Systemic Fungal Infections List the two main types Amphotericin B - Broad-spectrum antifungal - Highly toxic medication - Black box warning: Use in life-threatening infections only - Administered IV only: refusion reactions are common - Premedicate: acetaminophen plus diphenhydramine Azoles ie, Ketoconazole - Broad-spectrum antifungals - Inhibit CYP450 Superficial Infections: 1. The superficial mycoses are caused by two groups of organisms 2. Dermatophytoses are generally confined to the 1. Candida species and dermatophytes-ie, ringworm 2. skin, hair, and nails. dermatophytes are more common than superficial infections with Candida Know how to treat Different types of ○ tinea pedis (ringworm of the foot, or “athlete’s foot”), 1. Is the most 2. generally responds well to 1. Common fungal infection 2. topical allylamine ■ Terbinafine, Butenafine Know how to treat Different types of ○ tinea corporis (ringworm of the body), 1. usually responds to a 2. Treatment should continue for 3. Severe infection may require 1. topical azole (Clotrimazole-Lotrimin) or allylamine (Terbinafine, Butenafine) or Ciclopirox (shampoo) 2. at least 1 week after symptoms have cleared. 3. a systemic antifungal agent (e.g., griseofulvin). Know how to treat Different types of ○ tinea cruris (ringworm of the groin), 1. responds well to 2. Treatment should continue for 3. If the infection is severely inflamed 1. topical allylamine/azole therapy. ■ Terbinafine, Butenafine, Clotrimazole - if severe 2. at least 1 week after symptoms have cleared. 3. a systemic antifungal drug (e.g. Clotrimazole) may be needed; topical or systemic glucocorticoids may be needed as well. Know how to treat Different types of ○ tinea capitis (ringworm of the scalp), 1. Is difficult to treat and (blank) drugs don't typically work 2. Usually responds well to 1. Topical 2. 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. ■ Griseofulvin, terbinafine Know how to treat Different types of Oral candidiasis, also known as thrush, is seen often. - Topical agents—nystatin, clotrimazole, and miconazole—are generally effective. • In the immunocompromised host, oral therapy with fluconazole or ketoconazole is usually required. Know how to treat Different types of Vagina - candida (vaginal yeast infection). Topical miconazole. Oral fluconazole Onychomycosis (infection of toenails) 1. Onychomycosis is difficult to eradicate and requires prolonged treatment. Infections may be caused by (blank) or (blank) 2. Onychomycosis may be treated with 1. by dermatophytes or Candida species. 2. oral allylamine/azole (terbinafine and itraconazole both are active against Candida species and dermatophytes) OR with topical ciclopirox-only active against dermatophyte Itraconazole-Azole ○ clinical uses ○ MOA Clinical Uses ○ is an alternative to amphotericin B for systemic mycoses and is the prototype for azole family. ○ also used in the oral tx of Onychomycosis-nail fungus MOA ○ itraconazole inhibits the synthesis of ergosterol, an essential component of the fungal cytoplasmic membrane. The result is leakage of cellular components Adverse reactions/High-Risk Patients • Adverse effects 1. Common ones are 2. Black Box Warning 3. Drug Interactions 3a. Avoid use with drugs metabolized by CYP3A4 3b. (blank drugs) can greatly reduce the absorption of oral itraconazole. 1. GI reactions (nausea, vomiting, diarrhea) are most common. Other reactions include rash, headache, abdominal pain, and edema (pg. 716). ○ serious effects: cardiac suppression and liver injury 2. Negative Inotropic Actions: can cause a transient decrease in ventricular EF%, should not be used for in pts with HF, a hx HF, or other indications of ventricular dysfxn 3a. (warfarin, dofetilide-Tikosin, cyclosporine, digoxin, quinidine-antiarrhythmic . 3b. Drugs that decrease gastric acidity—antacids, H2 antagonists, and PPIs— ○ administer at least 1 hour before itraconazole or 2 hours after Patient Teaching-Itraconazole 1. Patient Teaching Summary of Key Prescribing Considerations-Azoles 2. Baseline 3. Monitoring 4. Minimizing Adverse Effects: Avoid use with drugs metabolized by CYP3A4 1. Patient Teaching ○ Instruct patients to report signs of liver dysfunction. 2. tests of liver function. 3. AST/ALT, alkaline phosphate, bilirubin: Initially and then monthly. 4. (warfarin, cyclosporine, digoxin, quinidine) - Voriconazole and Phenobarbital should not be combined due to CYP450 induction Explain: ● Phenobarbital is a cytochrome P450 hepatic enzyme inducer -if given with Voriconazole plasma levels of Voriconazole are extremely lowered by phenobarbital Patient-Centered Care Across the Life Span-Antifungal Agents Infants • Nystatin is used to treat oral candidiasis in Children/adolescents • Many antifungal agents are used safely in children, Pregnant women • Risks and benefits must be considered for administration during Breastfeeding women • (blank) are lacking regarding most antifungals and breastfeeding. Older adults • Older adults have a higher risk for Infants • premature and full-term infants. Fluconazole is also used safely to treat systemic candidiasis in newborn infants. Children/adolescents • in lower doses. Side-effect profiles are similar to those of adults. Pregnant women • pregnancy. Breastfeeding women • Data; Most antifungals are considered safe in lower doses. The exception to this is ketoconazole-has high potential for hepatotoxicity-avoid in breastfeeding Older adults • achlorhydria (HCl acid in gastric secretions) than do younger individuals and may not predictably absorb some antifungal agents. In addition, common drugs prescribed to older adults, including warfarin, phenytoin, and oral hypoglycemic agents, are increased by azoles. Week 2 Anthelmintics Ch 83 1. Helminthiasis (worm infestation) is the most 2. The (blank) is a frequent site of infestation. Other sites include 1. common affliction of humans, affecting more than 2 billion people worldwide. 2. intestine; the liver, lymphatic system, and blood vessels. Infestation is frequently asymptomatic. The most common parasitic worms belong to three classes: 1. Nematoda (roundworms), 2. Cestoda (tapeworms) 3. Trematoda (flukes) 1. Nematode Infestations can be 2. Nematode Infestations are found mainly in 1. Intestinal: roundworm, Pinworm, Whipworm, Hookworm, & Threadworm - Extra-intestinal: Trichinosis; is acquired by eating undercooked pork, River Blindness-filarial (vector born) 2. worldwide; In the USA, isolated to rural areas without adequate sanitation 1. Cestode (Tapeworm) Infestations acquired by eating 2. Trematode (fluke) Infestations are acquired from 1. undercooked beef or pork undercooked fish that is infested with tapeworm larvae. 2. snails, which take up residence in the vascular system, primarily in veins of the intestines and liver. Diagnostics and monitoring for Anthelmintics see diagram - Identifying High-Risk Patients with the following drugs Mebendazole 1. The most concerning adverse effects are 2. Baseline tests include 3.. The WHO allows mebendazole to be used in the (blank) and (blank) trimesters 4. This is the drug of choice for most intestinal Nematodes/roundworms. This agent clears 1. bone marrow suppression and liver impairment; however, these are typically only a problem with high doses or prolonged treatment • Because bone marrow suppression and liver impairment may occur, patients with liver disease, anemia, bleeding disorders, and infections are at increased risk 2. Liver fxn, CBC and renal fxn 3. in the second and third trimesters, but not the first trimester, 4. infestation with pinworms, hookworms, and giant roundworms - Identifying High-Risk Patients with the following drugs Albendazole (pg. 774) - 1. Albendazole may cause 2. Baseline line tests include 3. Who's at increased risk 4. In the USA, the drug is approved only for 5. albendazole is used off-label for 1. Mild to moderate liver impairment & bone marrow Suppression causing agranulocytosis and pancytopenia. Liver impairment may increase risk. 2. Liver function/CBC- before each cycle of tx and 14 days later. 3. Patients with liver, kidney disease, anemia-bleeding disorders & infections are at increased risk 4. pork tapeworms and disease of the liver, lung, and peritoneum by dog tapeworms 5. Nematodes: (hookworms, pinworms, giant roundworms, whipworms, and pork roundworms cause of trichinosis) & Chinese liver flukes - Identifying High-Risk Patients with the following drugs Pyrantel pamoate 1. Neonates should NOT be given formulations with 2. Most adverse effects are 3. Pts at high risk of adverse effects are 4. Pyrantel pamoate is active against 1. benzyl alcohol or its derivatives as they can develop potentially fatal “gasping syndrome” 2. are GI reactions (N/V, diarrhea, stomach pain). Possible CNS effects include dizziness, drowsiness 3. Patients with liver impairment 4. intestinal nematodes. The drug is an alternative to mebendazole or albendazole for hookworms or pinworms - Identifying High-Risk Patients with the following drugs Ivermectin/Moxidectin 1. common Adverse Effects include 2. Patients at high risk for Adverse Effects include 3. Baseline tests include 4. Both are active against many nematodes & DOC 5. An advantage of moxidectin over ivermectin is 1. pruritus, rash, fever, lymph node tenderness, and bone and joint pain-when treated for onchocerciasis known as a Mazotti reaction 2. Patients with hypotension or taking antihypertensive drugs may be at risk for increased hypotension and falls 3. Ophthalmologic exam for evidence of eye infestation 4. for onchocerciasis (River Blindness) and ivermectin is DOC for intestinal strongyloidiasis & kills mites such as Scabies in immunocompromised patients. 5. It's safer in pregnancy; low risk of teratogenicity Patient-Cenetered Care Across The Life Span-Anthelmintics Children • There are inadequate studies in children taking most of these drugs. Pyrantel pamoate Pregnant Women • Praziquantel appears to be the safest Breast-Feeding Women • The WHO advises women taking Older Adults • There are no current Children • formulations containing benzyl alcohol or its derivatives should not be prescribed for neonates (causes gasping syndrome). Pregnant Women • of the anthelmintics. Moxidectin has also demonstrated apparent safety; however, it was only approved recently. Breast-Feeding Women • mebendazole and pyrantel pamoate to continue breastfeeding but advises caution with albendazole and ivermectin. The manufacturer of praziquantel advises women not to nurse on the day of tx and 72 hours after. Older Adults • contraindications for older adults taking these drugs; but this is due to insufficient data to determine safety Week 2 Antiviral Agents Non-HIV Ch 80 • Unlike bacteria, viruses require a host cell in order to replicate. Medications used to treat viral infections work by interrupting the viral replication process inside host cells Herpes Simplex Viruses and Varicella-Zoster • Herpes Simplex Virus (HSV) family; a group that includes • HSV causes infection of • VZV is the cause of • HSV, varicella-zoster virus (VZV), and cytomegalovirus (CMV). • the genitalia, mouth, face, and other sites. • chickenpox and herpes zoster (shingles) Acyclovir (Zovirax) 1. Oral: is used to tx 2. Topical: is used to tx 3. IV: is used to tx 1. HSV infection and suppression, VZV infection 2. orolabial HSV (cold sores) 3. severe HSV/VZV infection or for immunocompromised patients 1. Valacyclovir (Valtrex) Oral: is used to tx 2. Foscarnet IV only Used for 1. HSV infection and suppression, VZV infection 2. immunocompromised patients with HSV or VZV Patient-Centered Care Across the Life Span Systemic Drugs for HSV and VZV Infections Children • Acyclovir is approved for children as young Pregnant women • the use of acyclovir, famciclovir, and valacyclovir Breastfeeding women • It is recommended that women who are taking systemic drugs for HSV and VZV Older adults • There are no Children • as 3 months of age. Valacyclovir is approved for children 2 years of age. The safety and efficacy of foscarnet/famciclovir have not been established Pregnant women • in pregnant women did not find a significant increase in abnormal outcomes. Foscarnet is not recommended Breastfeeding women • should avoid breastfeeding. Older adults • contraindications for this age group; however, those with renal impairment should be started on lower doses, with dosage adjustments made cautiously. Older adults taking acyclovir/valacyclovir are at greater risk for adverse CNS effects. Treatment for Influenza • Influenza is a serious respiratory tract infection, caused mainly by • (blank) is the primary strategy for prevention of influenza • Treatment for many patients with influenza is supportive: fluids and rest. Medication therapy is indicated • seasonal strains of influenza A (there is also a B strain) • Vaccination; Annual vaccination is the best protection against influenza • for patients with severe symptoms or at high risk of complications Neuraminidase Inhibitors Examples: oseltamivir PO (Tamiflu), peramivir, and zanamivir-inhaled. 1. They are active against 2. Note: these drugs are not as adequate as 3. When used for treatment, dosing must begin early— 4. These drugs can be used 1. most strains of influenza A and influenza B 2. vaccination and should not be considered as a substitute 3. ideally no later than 2 days after symptom onse 4. prophylactically after exposure Life Span considerations for Neuraminidase Inhibitors 1. Oseltamivir (Tamiflu) is an oral drug approved in patients 2. Because of the harmful effects of influenza on the developing embryo and fetus 1. One year of age and older. 2. experts recommend oseltamivir for both prophylaxis and treatment in pregnant women Week 2 Antiviral Agents for HIV Ch 81 Characteristics of HIV • HIV is a retrovirus; to replicate, retroviruses must first transcribe • The principal cells attacked by HIV are • their RNA into DNA. The enzyme employed for this process is reverse transcriptase. • CD4 T-cells (helper T lymphocytes) Replication Cycle of Human Immunodeficiency Virus 1. Knowing the steps of replications is key to understanding Step 2—The lipid bilayer envelope of HIV fuses Step 3/4—HIV RNA is transcribed into single-stranded DNA and then Step 10—after budding off, HIV undergoes final maturation under the influence of 1. the mechanism of Antiretroviral therapy (ART) Step 2—with the lipid bilayer of the host cell membrane; enfuvirtide—works by blocking the fusion process Step 3/4—converted into double-stranded HIV DNA by HIV reverse transcriptase (Reverse Transcriptase inhibitors) NRTIs block these steps) Step 10—protease, an enzyme that cleaves HIV, functional forms. If protease fails to cleave these proteins, HIV will remain immature and noninfectious. (HIV protease is the target of protease inhibitors) There are five classes of Antiretroviral Drugs 1. Three types—(blank, blank & blank)—inhibit enzymes required for HIV replication. 2. The other two types—(blank & blank)—block viral entry into cell 3. reverse transcriptase inhibitors are subdivided into two groups: 1. reverse transcriptase inhibitors (NRTIs & NNRTIs), integrase strand transfer inhibitors (INSTIs), and protease inhibitors (PIs) 2. fusion inhibitors and CCR5 antagonists (1) nucleoside/nucleotide reverse transcriptase 3. nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs), and (2) nonnucleoside reverse transcriptase inhibitors (NNRTIs) Nucleoside/Nucleotide Reverse Transcriptase Inhibitors Examples:Abacavir, Didanosine & Zidovudine Spectrum • The NRTIs were the • The NRTIs are effective against both HIV-1 and HIV-2; however, Resistance • They are ineffective as monotherapy because Mechanism of Action • All NRTIs are prodrugs that inhibit HIV replication by suppressing Adverse effects • NRTIs share a core of adverse effects associated with mitochondrial toxicity Spectrum • first drugs used against HIV infection • their activity is greater for HIV-1 Resistance • resistance develops rapidly Mechanism of Action • synthesis of viral DNA by preventing reverse transcriptase from adding more bases Adverse effects • NRTIs can disrupt synthesis of mitochondrial DNA and can thereby impair mitochondrial function Specific Adverse effects of NRTIs • The FDA requires all NRTIs to carry black box warnings about this major consequence of mitochondrial impairment • NRTIs can cause (blank), referred to as fatty degeneration of the liver and hepatomegaly • Other adverse effects include • lactic acidosis • Hepatic steatosis which is caused by a decreased breakdown of fatty acids by mitochondria leading to fatty deposits in the liver. • pancreatitis and myopathies, which are likely tied to lactic acidosis Patient Teaching of Specific NRTIs • Abacavir - Inform patients of hypersensitivity reactions that are possible; Teach them common symptoms—. • Didanosine - Instruct patients to take didanosine 30 min before meals or 2 h after. Instruct patients to avoid mixing powder formulations with acid-containing beverages Also, inform patients about early signs of neuropathy including • Zidovudine - Instruct patients to report new or worsening symptoms of anemia such as • Abacavir - fever, rash, myalgia, arthralgia, nausea, vomiting, diarrhea, abdominal pain, pharyngitis, dyspnea, and cough—and instruct them to report these immediately • Didanosine - (numbness, tingling, or pain in hands and feet) and instruct them to report these immediately • Zidovudine -(pallor, weakness) or neutropenia (evidence of infection). To prevent exposure to illness, patients should be cautioned to avoid contact with people who are ill and to avoid areas where people may congregate in large numbers Patient Education Nucleoside/Nucleotide Reverse Transcriptase Inhibitors 1. Emphasize the need to avoid taking any 2. All NRTIs, (blank), may be taken without regard to meals. 3. Patients taking NRTIs are at risk of 4. Inform patients that, even when HIV RNA is undetectable, they are 1. OTC drugs or supplements without first checking with the provider to verify safety. Teach patients how to access and use drug interaction checkers 2. except didanosine 3. lactic acidosis and hepatic steatosis. Inform patients about symptoms—nausea, vomiting, abdominal pain, malaise, fatigue, anorexia, and hyperventilation—and instruct them to report these immediately. 4. still infectious and hence should avoid behaviors that can transmit HIV - Identifying High-Risk Patients with the following drugs • Didanosine can easily cause problems in pts with liver disease, • Zidovudine’s risk for hematologic toxicity is increased by • peripheral neuropathy, retinal disorders and/or optic neuritis; Didanosine's risk for pancreatitis is increased by a history of alcoholism or pancreatitis and by use of IV pentamidine • a low granulocyte count; low levels of hemoglobin, vitamin B 12 , or folic acid; and concurrent use of drugs that are myelosuppressive, nephrotoxic, or toxic to circulating blood cells Patient-Centered Care Across the Life Span-Nucleoside Reverse Transcriptase Inhibitors Children • Both stavudine and zidovudine are approved for neonates; Pregnant women • ART is recommended for all HIV-infected pregnant women to Breastfeeding women • Breastfeeding should be Older adults • Older patients taking didanosine have a higher risk for Children • 3 months: Abacavir and lamivudine • 2 years: Tenofovir • 6 years & weighing at least 20 kg: Didanosine Pregnant women • lower the viral load and decrease the risk of perinatal transmission. Didanosine, emtricitabine, and tenofovir have less risk than lamivudine, stavudine, and zidovudine. Abacavir is unk. Combined NRTIs during pregnancy increase the risk for lactic acidosis, which can be life threatening. Breastfeeding women • avoided by women with HIV because there is a danger of transmitting the virus. Older adults • developing pancreatitis than younger patients. Peripheral neuropathy may be increased for older patients taking stavudine. Protease Inhibitors (PIs) Example: lopinavir with ritonavir & saquinavir Spectrum • PIs are active against both HIV-1 and HIV-2; They are among the Resistance • PIs should never be used alone; rather, they should always be Mechanism of Action • Maturation is necessary for HIV to infect CD4 cells; immature forms are noninfectious. PIs prevent Drug Interactions • PIs can interact with drugs that inhibit or induce Adverse effects • There are several adverse effects that all PIs have in common. These include Spectrum • most effective antiretroviral drugs available Resistance • combined with at least one reverse transcriptase inhibitor, and preferably two Mechanism of Action • HIV maturation by blocking the HIV enzyme protease Drug Interactions • P450 enzymes, and with drugs that are substrates Adverse effects • hyperglycemia and the development of diabetes, lipodystrophy (fat redistribution), the elevation of serum transaminases, and decreased cardiac conduction velocity. They can also increase bleeding in patients with hemophilia Adverse effects of Lopinavir with ritonavir • Dangerous drug interactions, 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, nausea, vomiting, abdominal discomfort, indigestion, weakness. Adverse effects of Saquinavir • Dangerous drug interactions (including danger with ritonavir), PR interval prolongation, QT interval prolongation, All of the adverse effects of Lopinavir/ritonavir Plus exacerbation of comorbid hepatic disease, hyperlipidemia, nausea, vomiting, abdominal pain, diarrhea, fatigue Identifying High-Risk Patients-Saquinavir & lopinavir + ritonavir • Use atazanavir, saquinavir, and lopinavir/ritonavir with caution in • Avoid lopinavir/ritonavir and saquinavir in patients with • patients with structural heart disease, cardiac conduction disturbances, and ischemic heart disease, and in those taking other drugs that prolong the PR interval. • congenital long QT syndrome, and in those taking drugs that prolong the QT interval Patient-Centered Care Across the Life Span-Protease Inhibitors Children • Lopinavir/ritonavira may be given to infants as young as 14 days However: Pregnant women • Nelfinavir, ritonavir, and saquinavir are the Breastfeeding women • Breastfeeding should be Older adults • Data are lacking in patients 65 years and older consider Children • Lopinavir/ritonavir oral solution should not be given to preterm infants