Nursing NR 565WEEK 2 Midterm review Nursing NR 565WEEK 2 Midterm review

Nursing NR 565WEEK 2 Midterm review Nursing NR 565WEEK 2 Midterm review WEEK 2 Midterm review Know how to treat o Different types of Tinea Tinea pedis. 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, and dry their feet after bathing. Tinea corporis. 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 (e.g., griseofulvin). Tinea cruris. 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 (e.g., clotrimazole) may be needed; topical or systemic glucocorticoids may be needed as well. Tinea capitis. Tinea capitis is 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. o Oral candidiasis Oral candidiasis. 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. o Aspergillosis Voriconazole - Voriconazole and Phenobarbital should not be combined due to CYP450O Phenobarbital is a CYP450 inhibitors which can reduce the levels of drugs like voriconazole.  - Adverse reactions/Patient Teaching o Itraconazole Adverse effects. Itraconazole is well tolerated in usual doses. Gastrointestinal reactions (nausea, vomiting, diarrhea) are most common. Other reactions include rash, headache, abdominal pain, and edema. Itraconazole may also cause two potentially serious effects: cardiac suppression and liver injury. Cardiac suppression. Itraconazole has negative inotropic actions that can cause a transient decrease in ventricular ejection fraction. Cardiac function returns to normal by 12 hours after dosing. The drug may still be used to treat serious fungal infections in patients with heart failure but only with careful monitoring and only if the benefts clearly outweigh the risks. If signs and symptoms of heart failure worsen, itraconazole should be stopped. Black Box Warning Negative Inotropic Actions With Itraconazole Because of its negative inotropic actions, itraconazole should not be used for superfcial fungal infections (dermatomycoses, onychomycosis) in patients with heart failure, a history of heart failure, or other indications of ventricular dysfunction. Summary of Key Prescribing Considerations Azoles Therapeutic Goal: Treatment of systemic and superfcial mycoses. Baseline Data: Baseline tests of liver function.Monitoring: No recommended monitoring. Identifying High-Risk Patients: Use with great caution in patient with liver disease. Evaluating Therapeutic Effects: Monitor for indications of antifungal effects—reduction in fever, pain, or inflammation. Minimizing Adverse Effects: Instruct patients to report signs of liver dysfunction. Avoid use with drugs metabolized by CYP3A4 (warfarin, cyclosporine, digoxin, quinidine). o Nucleotide Reverse Transcriptase Inhibitors (NRTIs) Adverse Effects The NRTIs share a core of adverse effects associated with mitochondrial toxicity. Recall that mitochondria are cellular organelles that take in nutrients and convert them into adenosine triphosphate (ATP) for energy. NRTIs can disrupt synthesis of mitochondrial DNA and can thereby impair mitochondrial function. Lactic acidosis. A major consequence of mitochondrial impairment is lactic acidosis. Lactic acid accumulates because dysfunctional mitochondria cannot break down lactic acid. Symptoms include nausea, malaise, fatigue, anorexia, and hyperventilation (blowing off carbon dioxide can reduce acidosis). Left untreated, the syndrome can be fatal. Diagnosis is based on lactic acid measurement in arterial blood. The United States Food and Drug Administration (FDA) requires all NRTIs to carry black box warnings about this possibility, even though it is rare for most. Those for which this is most likely to occur are didanosine and stavudine. Hepatic steatosis. Hepatic steatosis (fatty degeneration of the liver) and hepatomegaly are also adverse effects of NRTIs. This is also associated with mitochondrial impairment because there is decreased breakdown of fatty acids by mitochondria leading to fatty deposits in the liver. Other adverse effects.NRTIs may also cause pancreatitis and myopathies, which are likely tied to lactic acidosis. Adverse effects of individual NRTIs are discussed separately. ▪ Example drugs of NRTIs At this time, seven NRTIs are available: abacavir [Ziagen], didanosine [Videx], emtricitabine [Emtriva], lamivudine [Epivir], stavudine [Zerit], tenofovir [Viread], and zidovudine [Retrovir]. They are commonly identifed by assigned abbreviations: abacavir (ABC), didanosine (ddI), emtricitabine (FTC), lamivudine (3TC), stavudine (d4T), tenofovir (TDF), and zidovudine (ZDV).  - Diagnostics & Monitoring for anthelmintics Summary of Key Prescribing Considerations Anthelmintic Drugsa Therapeutic Goal: To eradicate parasitic worm infestation Baseline Data: Confrmation of infestation. Pregnancy test. Drugs requiring additional baseline data are albendazole (liver function and complete blood count [CBC] with differential); mebendazole (liver function, CBC with differential, and renal function); praziquantel (liver function); and ivermectin and moxidectin (ophthalmologic exam for evidence of eye infestation). Monitoring: Drugs requiring monitoring (other than confrmation of a cure, if needed) are: albendazole (liver function and CBC with differential); mebendazole (liver function, CBC with differential, and renal function); praziquantel (liver function); and ivermectin andmoxidectin (ophthalmologic exam if abnormal at baseline). Identifying High-Risk Patients: o• Albendazole – Because bone marrow suppression, impaired liver function, and possibly renal function may occur, patients with liver or kidney disease, anemia, bleeding disorders, and infections are at increased risk. o• Mebendazole – Because bone marrow suppression and liver impairment may occur, patients with liver disease, anemia, bleeding disorders, and infections are at increased risk. o• 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. o• Praziquantel – Patients with cardiac disease, liver impairment, or seizure disorders are at increased risk for complications. o• Ivermectin and Moxidectin – Patients with hypotension or taking antihypertensive drugs may be at risk for increased hypotension and falls. Evaluating Therapeutic Effects: Follow-up testing confrms cure. Minimizing Adverse Effects: For most of these drugs, adverse reactions do not require special treatment. Mazzoti reactions can be treated with antihistamines and NSAIDs. Rarely, glucocorticoids are needed. Ensuring adequate hydration is important.  - Identifying High-Risk Patients with the following drugs o Albendazole: Albendazole o Target Organismso Albendazole (Albenza) is active against many cestode and nematode parasites, including larval forms of Taenia solium and Echinococcus granulosus. In the United States, the drug is approved only for (1) parenchymal neurocysticercosis caused by larval forms of the pork tapeworm, T. solium; and (2) cystic hydatid disease of the liver, lung, and peritoneum caused by larval forms of the dog tapeworm, E. granulosus. However, despite lack of FDA approval, albendazole is considered a drug of choice for infestation with hookworms, pinworms, whipworms, Chinese liver flukes, giant roundworms, and pork roundworms, the cause of trichinosis. o Mechanism of Action o Albendazole inhibits polymerization of tubulin and hence prevents the formation of cytoplasmic microtubules. As a result, microtubule-dependent uptake of glucose is prevented. o Adverse Effects o Albendazole is generally well tolerated. Mild to moderate liver impairment has occurred in 16% of patients, as indicated by elevation of liver transaminases in plasma. Liver function should be assessed before each cycle of treatment and 14 days later. o Albendazole suppresses bone marrow function and can, hence, cause granulocytopenia, agranulocytosis, and even pancytopenia. Liver impairment may increase risk. Blood cell counts should be obtained before each cycle of treatment and 14 days later. In postmarketing studies, some patients developed renal failure. This occurred rarely and the association with albendazole has not been established. o Albendazole is teratogenic in animals and hence should not be used during pregnancy. If pregnancy occurs, the drug should be discontinued immediately. o Mebendazole:Mebendazole Target Organisms Mebendazole (Emverm and Vermox) is a drug of choice for most intestinal roundworms. This agent clears infestation with pinworms, hookworms, and giant roundworms. Because of its relatively broad spectrum of action, mebendazole is especially useful for treatment of mixed infestations. Mechanism of Action Mebendazole prevents uptake of glucose by susceptible intestinal worms. Glucose deprivation results in immobilization followed by slow death. Because the worms die slowly, up to 3 days may elapse between treatment onset and complete clearance of parasites. Mebendazole does not influence glucose uptake or utilization by humans. Adverse Effects Systemic effects are rare at usual doses, perhaps because the drug is so poorly absorbed. The most concerning are bone marrow suppression and liver impairment; however, these are typically only a problem with high doses or prolonged treatment. In patients with massive parasitic infestations, transient abdominal pain and diarrhea may occur. o Pyrantel pamoate: Pyrantel Pamoate Target Organisms Pyrantel pamoate (Reese's Pinworm Medicine, Combantrin ) is active against intestinal nematodes. The drug is an alternative to mebendazole or albendazole for infestations with hookworms or pinworms. Mechanism of Action Pyrantel is a depolarizing neuromuscular blocking agent that causes spastic paralysis of intestinal parasites. The paralyzed worms are cleared in the feces.Adverse Effects 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, and metabolic acidosis. Otherwise, serious reactions are rare. The most common effects are GI reactions (nausea, vomiting, diarrhea, stomach pain, and cramps). Possible central nervous system effects include dizziness, drowsiness, headache, and insomnia. o Ivermectin: Ivermectin o Target Organisms o Ivermectin (Stromectol) is active against many nematodes. Currently, the drug has two approved indications: onchocerciasis (a major cause of blindness worldwide) and intestinal strongyloidiasis. Ivermectin is active against the tissue microfilariae of O. volvulus (the cause of onchocerciasis), but not against the adult form. However, because adults are unable to produce microfilariae that remain viable, they are not replaced. Ivermectin can also be used to kill mites and lice, although these parasites are not approved targets. In addition to its use in humans, ivermectin is used widely in veterinary medicine. o Mechanism of Action o Ivermectin disrupts nerve traffic and muscle function in target parasites by opening chloride channels on the cell surface, which allows chloride ions to rush into nerve and muscle cells. The resultant hyperpolarization of these cells causes paralysis followed by death. Host cells are not affected, because ivermectin is selective for chloride channels in parasites. o Adverse Effects o Patients treated for onchocerciasis commonly develop pruritus, rash, fever, lymph node tenderness, and bone and joint pain. This reaction, known as a Mazotti reaction, is an allergic and inflammatory response to the death of O.volvulus rather than a reaction to the drug. (Mazotti-type reactions do not occur in patients treated for strongyloidiasis.) Abdominal pain and headache are seen in less than 5% of patients. Hypotension develops rarely. o Ivermectin is teratogenic in mice, rats, and rabbits. Cleft palate is the most common effect. There are no adequate data on teratogenesis in humans. Until more is known, ivermectin should be avoided during pregnancy. o Moxidectin: Moxidectin Target Organisms Moxidectin (Moxidectin) received the FDA approval for treatment of onchocerciasis due to O. volvulus in 2018. Activity against other helminths is unknown at this time. Mechanism of Action The exact mechanism of moxidectin is unknown, but the end result, like ivermectin, is increased cellular permeability followed by influx of calcium. Also, like ivermectin, the resultant hyperpolarization leads to paralysis. Adverse Effects Patients typically experience the flu-like symptoms of the Mazotti-response associated with death of the microflariae during the frst week. Adverse effects mirror those of ivermectin. Early studies suggest that a major advantage over ivermectin is moxidectin's apparent decreased risk for teratogenesis. In animal studies with rats (at 15 times the human dose) and rabbits (at 24 times the human dose), there were no signifcant effects on the embryo or fetus. Human studies are lacking, though, and we do not yet know what postmarketing studies may reveal. o Didanosine:Patient-Centered Care Across the Life Span Nucleoside Reverse Transcriptase Inhibitors Life Stage Considerations or Concerns Children Both stavudine and zidovudine are approved for neonates. Abacavir and lamivudine are approved for infants as young as 3 months. Tenofovir is approved for children age 2 and older. Didanosine is approved for children 6 years and older weighing at least 20 kg. Pregnant women Antiretroviral therapy is recommended for all HIV-infected pregnant women to lower the viral load and decrease the risk of perinatal transmission. The choice of antiretroviral drug for the pregnant woman must consider not only the risk for harm to the fetus from the drug but also the risk for harm to the fetus from the adverse effects tied to the drug. Didanosine, emtricitabine, and tenofovir are associated with less risk than lamivudine, stavudine, and zidovudine. Less is known about abacavir, but there are currently no known long-term adverse effects to the fetus despite a high level of placental transfer. Combined NRTIs during pregnancy increase the risk for lactic acidosis, which can be life threatening. Breastfeeding women Breastfeeding should be avoided by women with HIV because there is a danger of transmitting the virus. Older adults Older patients taking didanosine have a higher risk for developing pancreatitis than younger patients. Peripheral neuropathy mayLife Stage Considerations or Concerns be increased for older patients taking stavudine. o Zidovudine: Zidovudine Instruct patients to report new or worsening symptoms of anemia (e.g., 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. o Lopinavir:  Lopinavir/ritonavir oral solution is contraindicated for fullterm infants (until 14 days after birth) and preterm infants (until 14 days after their predicted due date).  • Use atazanavir, saquinavir, and lopinavir/ritonavir with caution in patients with structural heart disease, cardiac conduction disturbances, and ischemic heart disease, and in those taking other drugs that prolong the PR interval.  • Avoid lopinavir/ritonavir and saquinavir in patients with congenital long QT syndrome, and in those taking drugs that prolong the QT interval.  - Adverse Effects o Albendazole o Pyrantelpamoate: o Mebendazole o Ivermectin o Moxidectino Lopinavir/ritonavir see above!! o Saquinavir:  Use atazanavir, saquinavir, and lopinavir/ritonavir with caution in patients with structural heart disease, cardiac conduction disturbances, and ischemic heart disease, and in those taking other drugs that prolong the PR interval.  • Avoid lopinavir/ritonavir and saquinavir in patients with congenital long QT syndrome, and in those taking drugs that prolong the QT interval. o Enfuvirtide Adverse effects Injection-site reactions. In clinical trials, ISRs developed in 98% of patients, usually within the frst week of treatment. Principal manifestations are pain and tenderness, erythema and induration, nodules or cysts, pruritus, and ecchymosis (small hemorrhagic spots). Although generally mild to moderate, symptoms can also be severe. In 17% of patients, individual ISRs persisted more than 7 days. Because ISRs are both common and long lasting, 23% of patients had six or more ongoing ISRs at any given time. The intensity of ISRs can be reduced by rotating the injection site, avoiding sites with an active ISR, and avoiding unnecessarily deep injections. If a severe ISR occurs, or if local infection develops, patients should seek immediate medical attention. Pneumonia. Enfuvirtide appears to increase the risk for bacterial pneumonia. Patients should be informed about signs of pneumonia (cough, fever, breathing difficulties), and instructed to report them immediately. Enfuvirtide should be used with caution in patients who have pneumonia risk factors: low initial CD4 cell counts, high initial viral load, IV drug use, smoking, and a history of lung disease.Hypersensitivity reactions. Because enfuvirtide is a foreign peptide, it can trigger hypersensitivity reactions. Typical symptoms, which may occur individually and in combination, are rash, fever, nausea, vomiting, chills, rigors, hypotension, and elevated serum transaminases. Enfuvirtide has also been associated with respiratory distress, glomerulonephritis, Guillain-Barré syndrome, and primary immune complex reaction, all of which may be immune mediated. If a systemic hypersensitivity reaction occurs, enfuvirtide should be discontinued immediately and never used again.  - Lifespan Considerations o Which medications are safe during pregnancy or childhood Patient-Centered Care Across the Life Span Antifungal Agents Life Stage Patient Care Concerns Infants Nystatin is used to treat oral candidiasis in premature and 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 and benefits must be considered forLife Stage Patient Care Concerns administration during pregnancy. Breastfeeding women Data are lacking regarding most antifungals and breastfeeding. Most antifungals are considered safe in lower doses. The exception to this is ketoconazole. Because it has high potential for hepatotoxicity, it should be avoided in breastfeeding women. Older adults Older adults have a higher risk for achlorhydria 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. Patient-Centered Care Across the Life Span Nonnucleoside Reverse Transcriptase Inhibitors Life Stage Considerations or Concerns Children Nevirapine may be given to infants as young as 15 days. Efavirenz is approved for children older than 3 months and weighing at least 3.5 kg. Etravirine may be given to children who are 3 years and older. Safety and efficacy have not been established for rilpivirine and, for delavirdine, safety has not been established for patientsLife Stage Considerations or Concerns younger than 16 years. Pregnant women Antiretroviral therapy is recommended for all HIV-infected pregnant women to lower the viral load and decrease the risk of perinatal transmission. Etravirine, nevirapine, and rilpivirine are among the safest drugs in this category. Delavirdine carries a slightly higher risk for complications. Efavirenz is teratogenic. Pregnancy must be ruled out before efavirenz is used. For women capable of becoming pregnant, two forms of contraception are recommended during treatment and for 3 months after treatment is discontinued. Breastfeeding women Breastfeeding should be avoided by women with HIV because there is a danger of transmitting the virus. Older adults Each drug in this category identified insufficient numbers of older adults in clinical trials. Consider individual patient status regarding cardiac, hepatic, and renal status or comorbidities that may necessitate alternate regimens. Patient-Cenetered Care Across The Life Span AnthelminticsaLife Stage Considerations or Concerns Children There are inadequate studies in children taking most of these drugs. Pyrantel pamoate formulations containing benzyl alcohol or its derivatives should not be prescribed for neonates. As with all drugs the benefits of treatment must be weighed against the risk of adverse effects. Pregnant Women Praziquantel appears to be the safest of the anthelmintics. No abnormalities occurred in animal studies. Moxidectin has also demonstrated apparent safety; however, it was only approved in June 2018 and post-marketing studies are unavailable. Animal reproduction studies have demonstrated abnormalities for mebendazole, albendazole, and ivermectin; however, the risk to humans has not been established. The World Health Organization (WHO) allows use of mebendazole, albendazole, and pyrantel pamoate in the second and third trimesters, but not the first trimester, and does not recommend the use of ivermectin and diethylcarbamazine as treatment for women who are pregnant. BreastFeeding Women The WHO advises women taking mebendazole and pyrantel pamoate to continue breastfeeding but advises caution with albendazole and ivermectin. The manufacturer of pyrantel pamoate, however, does not recommend breastfeeding when taking this drug. The manufacturer of praziquantel notes that significant amounts of the drug are excreted into breast milk and advises that women not nurse on the day of praziquantel treatment and during the subsequent 72 hours. Data are lacking for moxidectin.Life Stage Considerations or Concerns Older Adults There are no current contraindications for older adults taking these drugs; however, because there are relatively few studies on the effects of these drugs on older adults, insufficient data are available to determine safety. - How to measure therapeutic effect of HIV therapy Summary of Key Prescribing Considerations Drugs for Human Immunodeficiency Virus Infection Therapeutic Goal: Treatment has five goals: (1) maximal and long-lasting suppression of viral load, (2) restoration and preservation of immune function, (3) improved quality of life, (4) reduction of HIV-related morbidity and mortality, and (5) prevention of HIV transmission. Baseline Data: In addition to a complete history and physical exam: CD4 count, HIV viral load, resistance testing, HBsAb, HBsAg, HBcAb total, HCV antibody, serum Na, K, HCO3, Cl, BUN, creatinine, estimated glomerular filtration rate, ALT, AST, total bilirubin, CBC with differential, fasting lipid profile, fasting glucose or hemoglobin A1c, urinalysis, pregnancy test if capable of becoming pregnant, HLA-B*5701 testing if considering abacavir, tropism testing if considering maraviroc, and serum phosphorus if considering tenofovir for patients with chronic kidney disease. Monitoring: See Box 81.2. Identifying High-Risk Patients:  • Didanosine's risk for pancreatitis is increased by a history of alcoholism or pancreatitis and by use of IV pentamidine.  • Zidovudine's risk for hematologic toxicity is increased by a low granulocyte count; low levels of hemoglobin, vitamin B12, or folic acid; and concurrent use of drugs that are myelosuppressive, nephrotoxic, or toxic to circulating blood cells. • Lopinavir/ritonavir oral solution is contraindicated for full-term infants (until 14 days after birth) and preterm infants (until 14 days after their predicted due date).  • Use atazanavir, saquinavir, and lopinavir/ritonavir with caution in patients with structural heart disease, cardiac conduction disturbances, and ischemic heart disease, and in those taking other drugs that prolong the PR interval.  • Avoid lopinavir/ritonavir and saquinavir in patients with congenital long QT syndrome, and in those taking drugs that prolong the QT interval.  • Use enfuvirtide with caution in patients who have pneumonia risk factors: low initial CD4 cell counts, high initial viral load, IV drug use, smoking, and a history of lung disease.  • Patients with elevated liver function and cardiovascular disease who take maraviroc must be monitored carefully. Evaluating Therapeutic Effects: HIV RNA Success is indicated by a reduction in plasma HIV RNA. With ART, plasma HIV RNA should decline to 10% of baseline within 2 to 8 weeks. After 16 to 20 weeks of treatment, plasma HIV RNA should reach its minimum. Ideally, the minimum will be undetectable with sensitive assays. CD4 T-Cell Counts As viral load decreases, CD4 T-cell counts may rise, indicating some restoration of immune function. Additional Notes:  - Drugs that decrease gastric acid should be administered at least 2 hours apart from other drugs due to decreased drug absorption.  - Prompt recognition of liver injury is essential with oral antifungal drugs. AST, ALT, alkaline phosphatase, and bilirubin should be monitored prior to initiation of therapy, monthly for 3 to 4 months, and frequently thereafter during treatment.