B. Riordian. School of the Art Institute of Chicago.
Recommendations to decrease nephrotoxicity effects of cyclosporine generic 30 mg prevacid fast delivery, oral contraceptives buy 15 mg prevacid amex, salicylates order 30 mg prevacid otc, and are listed in the section on Use in Renal Impairment; those warfarin, probably by inducing hepatic drug-metabolizing en- to decrease fever and chills include premedication with zymes and accelerating their metabolism. A test dose is often given, but this parenteral agents, safety, effectiveness, and guidelines for use does not reliably predict or rule out anaphylaxis, which have not been established. In addition, some agents have no is a rare adverse effect of both conventional and lipid established dosages and others have age restrictions. These in- used to treat anemia if the client has a low plasma level clude conventional and lipid formulations of amphotericin B, of erythropoietin. As in other pop- ulations receiving these drugs, children should receive the lowest effective dosage and be monitored closely for adverse Effects of Antifungals on Other Drugs effects. The safety and efﬁcacy of caspofungin in children have not been established. Amphotericin B increases effects of cyclosporine (nephro- toxicity), digoxin (risk of hypokalemia and resultant cardiac dysrhythmias), nephrotoxic drugs (eg, aminoglycoside anti- Use in Older Adults biotics), skeletal muscle relaxants (amphotericin B-induced hypokalemia may enhance muscle relaxation), and thiazide Speciﬁc guidelines for the use of antifungal drugs have not and loop diuretics (risk of hypokalemia). Azoles inhibit the metabolism of many drugs (by inhibit- Virtually all adults receiving IV amphotericin B experi- ing cytochrome P450 drug-metabolizing enzymes in the liver ence adverse effects. With the impaired renal and cardio- and small intestine, especially 3A4 enzymes) and therefore in- vascular functions that usually accompany aging, older adults crease their effects and risks of toxicity. These drugs include are especially vulnerable to serious adverse effects. They benzodiazepines (alprazolam, midazolam, triazolam), cal- must be monitored closely to reduce the incidence and sever- cium channel blockers (felodipine, nifedipine), cyclosporine, ity of nephrotoxicity, hypokalemia, and other adverse drug phenytoin, statin cholesterol-lowering drugs (lovastatin, sim- reactions. Lipid formulations are less nephrotoxic than the vastatin), sulfonylureas, tacrolimus, theophylline, warfarin, conventional deoxycholate formulation and may be preferred vincristine, and zidovudine. Azole drugs should probably be stopped if CHAPTER 40 ANTIFUNGAL DRUGS 609 hypertension, edema, or hypokalemia occur. Plasma drug levels should be monitored and conazole has been associated with heart failure, a common dosage should be adjusted to maintain blood levels below condition in older adults. Terbinafine clearance is reduced by 50% in clients with significant renal impairment (CrCl of 50 mL/ minute or less). Use in Clients With Cancer Clients with cancer are at high risk for development of seri- Use in Hepatic Impairment ous, systemic fungal infections. In clients receiving cytotoxic anticancer drugs, antifungal therapy is often used to prevent Although the main concern with amphotericin B is nephro- or treat infections caused by Candida and Aspergillus organ- toxicity, it is recommended that liver function tests be moni- isms. For prophylaxis, topical, oral, or IV agents are given be- tored during use.
Based upon two phase II tri- als in previously treated NSCLC patients discount prevacid 30 mg fast delivery, in which response rates of 10–20% were found buy prevacid 30mg low price,35 order prevacid 15 mg without a prescription,36 Stage IV Disease two phase III trials were initiated comparing Several meta-analyses have demonstrated that chemotherapy plus an EGFr inhibitor, ZD1839, chemotherapy improves survival in patients with with chemotherapy in untreated NSCLC. Some- metastatic NSCLC (approximately 10% 1-year what surprisingly, no beneﬁt was observed in these trials. These include, among TREATMENT: SMALL-CELL LUNG CANCER others, vinorelbine, the taxanes (docetaxel and paclitaxel), gemcitabine and the topoisomerase Small-cell lung cancer differs from NSCLC in I inhibitors (irinotecan and topotecan). Ran- a number of important ways: (1) it has a more domised studies have shown that these agents rapid clinical course and natural history, with the improve survival when combined with cisplatin, rapid development of metastases, symptoms and as compared to cisplatin alone,27,28 or the other death; (2) it exhibits features of neuroendocrine agent alone. Because of the (cyclophosphamide, adriamycin and vincristine) rapid development of distant disease and its as second-line therapy revealed no difference in extreme sensitivity to the cytotoxic effects of response rates, duration of response, or survival chemotherapy, this mode of therapy forms the between the two groups. Chemotherapy plus Chest Irradiation First-Line Therapy Numerous studies have been done with chemo- A number of combination chemotherapeutic reg- therapy and thoracic radiotherapy for patients imens are available for SCLC. Conﬂicting results have chemotherapy regimens, overall response rates of been attributed to differences in chemother- 75–90% and complete response rates of 50% apy regimens and different schedules integrat- for localised disease can be anticipated. Despite these high response radiation does result in a small but signiﬁcant rates, however, the median survival time remains improvement in survival and major control of about 14 months for limited-stage disease and the disease in the chest, although no conclusions 7–9 months for extensive-stage disease. Less could be made regarding the optimal sequencing than 5% of extensive-stage patients have long- of chemotherapy and thoracic radiation. A phase III randomised trial has been reported Fractionation of Radiotherapy: For limited-stage in abstract form, in which patients with SCLC SCLC, thoracic radiotherapy has been known were randomised to the control arm of etoposide to improve survival, but the best ways of inte- and cisplatin, versus cisplatin and the topoiso- 39 grating chemotherapy and thoracic radiotherapy merase I inhibitor, irinotecan. In order to settle this question, a and 1-year survival was 420 days and 60% in phase III randomised clinical trial was conducted the cisplatin/irinotecan arm and 300 days and in which 417 patients with limited SCLC were 40% in the cisplatin/etoposide arm. If ongo- randomised to receive a total of 45 Gy of radio- ing phase III studies conﬁrm these results, cis- therapy, either twice-daily over a 3-week period or platin/irinotecan would become the ﬁrst combi- once-daily over a 5-week period, concurrently with nation of chemotherapy to improve survival over 43 four 21-day cycles of cisplatin plus etoposide. Twice-daily radiotherapy improved median sur- vival as compared with once-daily radiotherapy Second-Line Therapy (23 months vs. However, No curative regimens for patients with recur- grade 3 or 4 oesophagitis was signiﬁcantly more rent disease have been identiﬁed. In general these designs are based on the ily based on Bayesian statistical modelling of the paradigm that with the increased myelosuppres- dose–toxicity relationship with a targeted toxicity sion, tumour cells are more likely to be killed, probability for the MTD. With radiotherapy con- leading to shrinkage of tumours, and that there cerned with late-onset toxicities as the primary is a monotonically increasing dose–response and endpoint, the standard dose-escalation design for dose–toxicity relationship. It is also assumed that phase I clinical trials is inadequate because of the tumour shrinkage will eventually lead to clinical long-term follow-up required for late-onset toxic- beneﬁt such as prolonged survival or improved ities associated with radiotherapy. In essence, tumour shrinkage has toxicities, the continual reassessment method has served as a surrogate for clinical beneﬁt.
Such issues as patient satisfaction trials where different packages of management and quality of life are obviously beyond the scope are evaluated purchase 15mg prevacid with amex, such as in the comparison of a self- of a self-controlled design prevacid 30mg visa. It is surprising that administered topical product for psoriasis with self-controlled designs have been the preferred hospital-based therapy like phototherapy prevacid 30 mg mastercard. Tradi- design in situations like topical immunotherapy tionally, motivation is seen as a characteristic of of alopecia areata or short-contact therapy of the patient that is assumed not to change with the psoriasis where patient satisfaction and mainte- nature of the intervention. We have PHASE III TRIALS already mentioned that the boundary between disease and non-disease is particularly shady in From phase III studies we request randomised dermatology. They there is a need to ensure that patient information should study those clinical outcomes that are and motivations are taken into proper considera- of major interest to physicians and patients (as tion when designing and analysing clinical trials 226 TEXTBOOK OF CLINICAL TRIALS on skin disorders. The issue is not only a mat- with variations in disease severity over time. A distinction should situations where a variable time-course of the be drawn between an informed choice based on clinical condition is expected, it may be advis- factual data–such as a reliable estimate of the able to proceed with sequential evaluations using risks and beneﬁts of interventions–and attitudes standardised criteria to judge the stability of the towards treatment based on emotional aspects disease over time. In recent years, a number tion about the stability of the clinical condition is of design variants on the traditional randomised often neglected in clinical trial reports. They include the partially psoriasis examined more than 60 clinical trials between 1988 and 198921 and documented that randomised patient preference design and the so-called randomised consent or Zelen design. This is rarely found in clinical trial Dutch patients affected by psoriasis considered reports concerning skin disorders. An example of the safety issue and long-term management as how far exclusion criteria may operate and limit more important than fast clearing. There trial, only 396 were eventually selected to be is room for testing study designs that allow for randomised in the treatment or placebo group. Such exclusion must be a warning when interpret- ing the actual effectiveness of Dabao on males affected by alopecia androgenetica. It is quite ENTRY CRITERIA plausible that a similar selection process operates in many RCTs concerning skin disorders. The deﬁnition of the study population is of par- ticular importance in dermatology where large PLACEBO USE variations in disease severity and different clini- cal subgroups may exist–e. In addition, there may be problems placebo in randomised control trials. As a consequence, ing the active therapy does not necessarily affect the use of placebo should be proscribed when the long-term prognosis. In spite issues of symptomatic relief and moderate sever- of these principles, studies which breach the ity disorders are commonly encountered in der- ethical principle are still commonly conducted matology and, in fact, a large number of placebo- with the approval of regulatory agencies and controlled RCTs are conducted in this area even institutional review boards.
For pedicu- sexual partners need simultaneous treatment to prevent losis cheap 15 mg prevacid with visa, permethrin is available as a 1% over-the-counter liquid reinfection generic 15 mg prevacid mastercard. For scabies buy generic prevacid 30 mg on-line, a 5% cream permethrin cream (Elimite) is • With pubic (crab) lice, assess sexual activity. For scabies, a single application of be transmitted by sexual and other close contact and by 5% permethrin cream is considered curative. The person may be asymptomatic, have people with a history of allergy to ragweed or chrysanthemum nausea, vomiting, diarrhea, abdominal cramping, and flowers should use it cautiously. The most frequent adverse weakness, or experience symptoms from ulcerations of effect is pruritus. With pediculosis, clothing and bedding biasis is diagnosed by identifying cysts or trophozoites should be sterilized by boiling or steaming and seams of E. Characteristic Gamma benzene hexachloride (Lindane) is a second- paroxysms of chills, fever, and copious perspiration may line drug for scabies and pediculosis. During acute malarial at- people who have hypersensitivity reactions or resistance to tacks, the cycles occur every 36 to 72 hours. It is applied topically, and sub- symptoms include nausea and vomiting, splenomegaly, stantial amounts are absorbed through intact skin. CNS toxi- hepatomegaly, anemia, leukopenia, thrombocytopenia, city has been reported with excessive use, especially in infants and hyperbilirubinemia. The drug is available in a 1% concentration in fying the plasmodial parasite in peripheral blood smears a cream, lotion, and shampoo. Women usually have vaginal burning, in the treatment of head lice, and Pyrethrin preparations itching, and yellowish discharge; men may be asympto- (eg, Barc, RID) are available over the counter as gels, sham- matic or have symptoms of urethritis. The condition is poos, and liquid suspensions for treatment of pediculosis. Heavy infestations produce symptoms according to the particular parasitic worm. Hookworm, roundworm, Nursing Process and threadworm larvae migrate through the lungs and may cause symptoms of pulmonary congestion. The Assessment hookworm may cause anemia by feeding on blood from Assess for conditions in which antiparasitic drugs are used. Large masses of roundworms or 12 ﬂuenced by many variables (eg, geographic location, per- tape-worms may cause intestinal obstruction. The major sonal hygiene, environmental sanitation), some useful symptom usually associated with pinworms is intense questions may include the following: itching in the perianal area (pruritus ani). Helminthi- • Does the person live in an institution, an area of poor asis is diagnosed by microscopic identification of par- sanitation, an underdeveloped country, a tropical re- asites or ova in stool specimens.