NR 565 NR565 WEEK 2 Midterm review Completed A++++

NR 565 NR565 WEEK 2 Midterm review Completed A++++ 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 t ...

NR 565 NR565 WEEK 2 Midterm review Completed A++++ 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.