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the writers responsibility essay Hepatic metabolism and biliary excretion account for the majority of paclitaxel’s elimination. Paclitaxel has demonstrated activity in several solid tumors. Considerable variability exists in paclitaxel dosing, from weekly 1-hour infusions to 24-hour infusions administered every 3 weeks. The diluent for paclitaxel, cremophor el, is composed of ethanol and castor oil. Infusions must be prepared and administered in non–polyvinyl chloride– containing bags and tubings, and solutions must be filtered. Patients receive dexamethasone, diphenhydramine, and an h2 blocker to prevent hypersensitivity reactions caused by cremophor el. Patients also may have asymptomatic bradycardia during the infusion. Approximately 3 to 5 days after administration, patients may complain of myalgias and arthralgias that may last several days. Myelosuppression, flushing, neuropathy, ileus, and total-body alopecia are other common side effects. Because paclitaxel is a substrate for cyp 3a4, steady-state concentrations of paclitaxel were 30% lower in patients receiving phenytoin than in patients not receiving phenytoin. Paclitaxel clearance was decreased by 33% when it was administered after cisplatin, so paclitaxel is administered before cisplatin. A nanoparticle albumin-bound nab-paclitaxel product is also available for the treatment of metastatic breast cancer resistant to conventional chemotherapy or progressing within 6 months of receiving a regimen containing an anthracycline. The nabpaclitaxel formulation uses nanotechnology to combine human albumin with paclitaxel allowing for the delivery of an insoluble drug in the form of nanoparticles. This unique formulation allows for an increased bioavailability and higher intracellular concentrations of the drug. It does not have the serious hypersensitivity reactions encountered with paclitaxel solubilized in cremophor el, so premedication with h1 and h2 blockers and steroids is not necessary. There is also a significantly lower incidence of severe neutropenia when compared to paclitaxel. The dose is infused over 30 minutes and does not require a special iv bag, tubing, or filter. The dosing of this product is different from that of the original paclitaxel, so practitioners need to be aware of which product is being prescribed. The pharmacokinetics of the albumin-bound paclitaxel displays a higher clearance and larger volume of distribution than paclitaxel. The drug is eliminated primarily via fecal excretion. 17 bone marrow suppression, neuropathy, ileus, arthralgias, and myalgias still occur. Docetaxel has activity in the treatment of several solid tumors also. Dexamethasone, 8 mg twice daily for 3 days starting the day before treatment, is used to prevent the fluid-retention syndrome associated with docetaxel and possible hypersensitivity reactions. The fluid-retention syndrome is characterized by edema and weight gain that is unresponsive to diuretic therapy and is associated with cumulative doses greater than 800 mg/m2. Myelosuppression, alopecia, and neuropathy are other side effects associated with docetaxel treatment. Cabazitaxel is a newer taxane used in combination with prednisone for the treatment of metastatic hormone-refractory prostate cancer in patients previously treated with a docetaxelcontaining treatment regimen. Cabazitaxel has shown to have similar adverse effects as paclitaxel and docetaxel. Premedication with an antihistamine, corticosteroid, and h2 antagonist to prevent hypersensitivity reactions is required. »» halichondrins eribulin mesylate is a nontaxane microtubule dynamics inhibitor.

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http://ccsa.edu.sv/study.php?online=thesis-and-dissertation-binding thesis and dissertation binding 2 linear growth velocity is reduced by less than half a centimeter per year and height after 1 year of treatment is decreased by less than 1 cm in children treated with low and medium dose ics. 21,22 a significant drug interaction causing cushing syndrome and adrenal insufficiency occurs when potent inhibitors of cyp3a4 (ritonavir, itraconazole, ketoconazole) are administered with high doses of ics. 18 poor adherence to ics treatment is common and contributes to uncontrolled asthma. 23 the slow onset of action and concerns about side effects are major deterrents to using these highly effective medications. Considerable variability in response to ics exists, with up to 40% of patients not responding to ics. This lack of response may be related to functional glucocorticoid-induced transcript 1 gene (glcci1) variant in some patients with asthma. 24 systemic corticosteroids prednisone, prednisolone, and methylprednisolone are the cornerstone of treatment for acute asthma not responding to an saba (see table 14–3 for recommended doses). 1,2 the onset of action for systemic corticosteroids is 4 to 12 hours. For this reason, systemic corticosteroids are started early in the course of acute exacerbations. The oral route is preferred in acute asthma. There is no evidence that intravenous corticosteroid administration is more effective. Therapy 248  section 2  |  respiratory disorders table 14–5  estimated comparative daily dosages for inhaled corticosteroids for asthma2,32 low daily dose high daily dose ages 0–11 years ages 12 years and older ages 0–11 years ages 12 years and older 40 mcg, 1–2 puffs 80 mcg, 1 puff twice daily or 80 twice daily mcg, 1 puff twice dailya budesonide dpi 90 or 90 mcg, 1–2 180 mcg, 1 180 mcg/inhalation inhalations twice inhalation daily or 180 mcg, twice daily 1 inhalation twice dailya budesonide inhalation ages 0–4. 0. 25 mg n/a suspension for once or twice daily. Nebulization ages 5–11. 0. 25 0. 25 mg/2 ml, mg twice daily or 0. 5 mg/2 ml, 0. 5 mg once daily 1 mg/2 ml ciclesonide hfa 80, 80 mcg, 1 puff once 160 mcg, 1 puff 160 mcg/puff or twice daily or once or twice 160 mcg, 1 puff daily dailyb flunisolide hfa 80 mcg, 1 puff twice 80 mcg, 2 puffs 80 mcg/puff dailya twice daily 80 mcg, 2 puffs twice dailya 80 mcg, 3 puffs twice daily 80 mcg, > 2 puffs twice dailya 80 mcg, > 3 puffs twice daily 180 mcg, 2 inhalations twice dailya 180 mcg, 2–3 180 mcg, inhalations twice > 2 daily inhalations twice dailya 180 mcg, > 3 inhalations twice daily fluticasone furoate n/a dpi 100 or 200 mcg/ inhalation fluticasone 44 mcg, 1–2 puffs propionate hfa twice daily (mdi) 44, 110, or 220 mcg/puff 100 mcg, 1 inhalation daily n/a 200 mcg, 1 inhalation daily 110 mcg, 1 puff twice daily 110 mcg, 1 puff twice daily 110 mcg, 2 puffs twice daily or 220 mcg, 1 puff twice daily fluticasone propionate dpi 50, 100, or 250 mcg/ inhalation 100 mcg, 1 inhalation twice daily 100 mcg, 2 inhalations twice dailya 250 mcg, 1 inhalation twice daily 220 mcg, 1 inhalation daily 110 mcg, 1–2 220 mcg, 1 inhalations inhalation twice daily or twice daily or 2 220 mcg, 1 inhalations daily inhalation twice dailyc medication ages 0–11 years ages 12 years and older medium daily dose beclomethasone hfa (mdi) 40 or 80 mcg/puff 50 mcg, 1–2 inhalations twice daily or 100 mcg, 1 inhalation twice dailya mometasone dpi 110, 110 mcg, 1 220 mcg/inhalation inhalation dailyc combined ics/laba fluticasone/ 100/50 mcg, salmeterol dpi 1 inhalation 100/50 mcg, twice dailyd 250/50 mcg, 500/50 mcg. Hfa (mdi) 45/21 mcg, 115/21 mcg, 230/21 mcg budesonide/ n/ab formoterol hfa (mdi) 80/4.

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