By T. Zarkos. Mercyhurst College.
INDIVIDUAL DRUGS Expectorants Individual decongestants discount 20mg atorlip-20 with amex, antitussives buy atorlip-20 20 mg on line, expectorants order atorlip-20 20mg on-line, and mu- Expectorants are agents given orally to liquefy respiratory se- colytics are listed in Drugs at a Glance: Nasal Decongestants, cretions and allow for their easier removal. Guaifenesin is the Antitussives, and Expectorants; selected combination prod- most commonly used expectorant. Several supplements are commonly used to prevent or treat Mucolytics symptoms of the common cold. Mucolytics are administered by inhalation to liquefy mucus in Echinacea preparations differ in chemical composition the respiratory tract. Solutions of mucolytic drugs may be neb- depending on which of the nine species or parts of the plant ulized into a face mask or mouthpiece or instilled directly into (eg, leaves, roots, whole plants) are used, as well as the sea- the respiratory tract through a tracheostomy. Sodium chloride solution and acetylcysteine (Mucomyst) are the only agents recommended for use as mucolytics. Acetylcysteine is effec- tive within 1 minute after inhalation, and maximal effects Nursing Notes: Apply Your Knowledge occur within 5 to 10 minutes. Oral acetylcysteine is widely used in the treatment of acetaminophen overdosage (see Chap. Joan, a college student, comes to the health clinic with cold symptoms (productive cough, low-grade fever, continuous nasal Cold Remedies discharge, and general malaise and discomfort). She states she went to the drugstore to buy some cold medicine, but there were so many different preparations that she was confused. Discuss Many combination products are available for treating symp- your recommendations for Joan, with their underlying rationale. Many of the products contain an CHAPTER 49 NASAL DECONGESTANTS, ANTITUSSIVES, AND COLD REMEDIES 731 Drugs at a Glance: Nasal Decongestants, Antitussives, and Expectorants Routes and Dosage Ranges Generic/Trade Name Adults Children Nasal Decongestants Ephedrine sulfate 0. Maximum, 6 doses/24 h 6–11 y: 2–3 sprays in each nostril no more often than q4h. Maximum 120 mg/24 h 12 y and older: Same as adults Topically, 2–3 sprays or drops of 0. Maximum 60 mg/24 h or 1% solution in each nostril no more often Topically, 2–3 sprays of 0. Pseudoephedrine (Sudafed, Dimetapp) Regular tablets, PO 60 mg q4–6 h 12 y and older: Same as adults for regular and Extended-release tablets, PO 120 mg q12h or extended release tablets 240 mg q24h. Maximum, 60 mg/24 h <2 y: Consult pediatrician Tetrahydrozoline (Tyzine) 0. Nonnarcotic Antitussive Dextromethorphan (Benylin DM, others) Liquid, lozenges, and syrup, 10–30 mg q4–8h. Sustained action liquid, 6–12 y: 30 mg q12h 2–5 y: 15 mg q12h Expectorant Guaifenesin (glyceryl guaiacolate) PO 100–400 mg q4h. Mucolytic Acetylcysteine (Mucomyst) Nebulization, 1–10 mL of a 20% solution or Acetaminophen overdosage, see literature 2–20 mL of a 10% solution q2–6h Instillation, 1–2 mL of a 10% or 20% solution q1–4h Acetaminophen overdosage, PO 140 mg/kg initially, then 70 mg/kg q4h for 17 doses; dilute a 10% or 20% solution to a 5% solution with cola, fruit juice, or water 732 SECTION 8 DRUGS AFFECTING THE RESPIRATORY SYSTEM TABLE 49–1 Representative Multi-Ingredient Nonprescription Cold, Cough, and Sinus Remedies Ingredients Trade Name Antihistamine Nasal Decongestant Analgesic Antitussive Expectorant Actifed Cold & Allergy Triprolidine Pseudoephedrine 2. Also, which constituents of the plants are cause adverse effects and about 90% of large doses is ex- pharmacologically active is unclear. Very little is absorbed and blood levels of Some studies indicating effectiveness of echinacea in vitamin C are raised only slightly. Most of the studies suggesting benefit are consid- controlled study showed no benefit of using echinacea for ered flawed in methodology. For example, although some preventing the common cold or respiratory infection. Thus, there is no convincing evidence that echi- Nursing Process nacea is effective. Moreover, the purity and potency of echinacea products are unknown or variable among prod- Assessment ucts.
The physiological function would then be the action (the application atorlip-20 20mg cheap, in mathematical terms) and the product would be the result of the function (the value of the function generic 20mg atorlip-20 with mastercard, in mathematical terms) that is often identiﬁed with the physiological function itself buy atorlip-20 20mg otc. Although this deﬁnition is general, it is unfortunately not operational. It is relatively easy to describe particular physiological functions such as vision, di- gestion, memorization, and so on, but it is far more di‰cult to give an operational deﬁnition of a physiological function in general. One possibility may be to deﬁne a physiological function in terms of a combinatorial set of functional interactions between structures. Such functional interactions are evidently speciﬁc since they de- scribe the action (whatever its nature) of one structure on another or, more precisely, the action of a source on a sink, after the action has undergone a transformation in the source. In addition, it has another important property, that of nonlocality, a notion somewhat more di‰- cult to appreciate since it stems from the structural hierarchy of the system (G. This may be explained as follows: (1) From a mathematical point of view, in a continuous representation, the action of one structure on another is necessarily the 134 G. This does not correspond to the action of one cell on another in physical space since a cell contains regions with specialized functions and therefore cannot be reduced to a point. Thus, other levels of organisation in the hierarchical system contribute to the working of a given struc- ture at a given level in the hierarchy. This is nonlocality, which is due to the choice of the representation, here a hierarchical representation. Equations that represent pro- cesses have then a di¤erent structure and must include nonlocal terms. The same reasoning applies to the dynamic processes of functional interactions operating, for example, between neural groups or between endocrine glands. In more general terms, this can be extended to the entire activity of the organism, provided that all the functional interactions involved are correctly represented. We may then formulate a hierarchical theory of functional organization as follows: In a multiple-level hierarchical system, each functional interaction is described by the transport of an activating and/or inhibiting signal (in the form of an action potential, a hormone, or some other type of interaction) between a source and a sink, and each physiological function results from a combination of such interactions. This idea can be conveniently expressed in terms of a ﬁeld theory according to which an operator transmits an interaction at a certain rate from a source to a sink situated in the space of units, with the source and the sink each being reduced to a point. This representa- tion constitutes the basis for the deﬁnition of a physiological function as the overall behavior of a group of structural units within a hierarchical system. From a mathematical point of view, a functional interaction is deﬁned as the inter- action between two of the p structural units ui and uj ði; j ¼ 1; pÞ of a formal biolog- ical system (FBS). One of the units, for example, the source ui, emits a signal that acts on the other, the sink uj, which in turn emits a substance after an eventual trans- formation (ﬁgure 7. This interaction, called an elementary function, is represented by cij and constitutes an element of the mathematical graph representing the orga- nization of the formal biological system (O-FBS). The dynamics of the functional interactions are then described by a system of equations of the type: cc_ ¼ f ðc ; c ;... The structural unit is deﬁned as the set of anatomical or physical elements inter- vening in the physiological function. Thus, from a functional point of view, a system made up of a set of elements, such as molecules, cellular organelles, cells, tissues, and organs, is represented by func- tional interactions and structural units. Mathematical Modeling of Neuromimetic Circuits 135 Source Sink Functional ui interaction uj (a) Structural Discontinuity Structure A Structure B (b) Non-local functional interaction Figure 7. Structural Discontinuities Functional interactions may be identiﬁed by the pres- ence of structural discontinuities. Suppose we have two structural units separated by a structural discontinuity. The interaction is propagated from one unit to the other across the discontinuity, which could, for example, be a membrane allowing active transport. The membrane is at a lower level in the structural hierarchy than the two interacting units. From the point of view of the dynamics of the functional interac- tion, we may say that this interaction consists of a certain physiological process oper- ating in the two units [located at r0 and r in the space of units, that is, the r-space, referred to as r0ðx0; y0; z0Þ and rðx; y; zÞ in the physical three-dimensional space], with a di¤erent physiological process being executed at a lower level in the structural discontinuity.
Cost-effectiveness models suggest that per arm generic 20 mg atorlip-20 with visa, comparing no post-surgical treatment to one-time screening colonoscopy between ages adjuvant treatment with either levamisole alone 50–54 years may be a rationale colorectal cancer or 5-FU plus levamisole cheap atorlip-20 20 mg amex. Given the novelty of GASTROINTESTINAL CANCERS 125 this result buy atorlip-20 20mg with amex, in a decision that likely would never infusion. Based on promising results in the be made in the current day, the investigative advanced disease setting (as discussed below), team decided to embark on a larger, conﬁrmatory multiple clinical trials have been conducted using trial prior to the release of the results to the regimens based on a long-term infusion with oncology community. Intergroup trial 0153 directly compared known as Intergroup trial 0035, enrolled over a bolus to an infusional 5-FU based regimen 1200 patients to the same three arms as the in a randomised Phase III trial of 1078 patients initial trial. Intergroup 0035 clearly demonstrated (terminated early at an interim analysis–original improved overall survival in patients treated with planned sample size of 1800 patients). Based on these results, with stage 3 colon cancer who are unable to two recent Phase III randomised trials in the enter a clinical trial should be offered adjuvant United States have used control arms of 6 months treatment with 5-FU plus levamisole unless there of bolus 5-FU plus leucovorin. Several of these trials included a areas – ﬁrst, to improving the treatment options no post-surgical treatment control arm, and thus available, and second, and relatedly, to tailoring these trials were closed prior to reaching their therapy to the individual patient. Included in area, for the time being, new studies will ran- this list of trials that were closed prematurely domise patients to treatments based on adding a were ﬁve Phase III randomised trials testing new treatment to a 5-FU and leucovorin regimen. The results from three of these 51 in the United States compared 5-FU and leucov- trials were pooled for analysis; the other two 52,53 orin to either a 5-FU, leucovorin and irinotecan were reported separately. In each of these (trial C89803) or 5-FU, leucovorin and oxali- analyses, adjuvant 5-FU plus leucovorin showed platin (trial C-06). In somewhat of a leap of faith, a survival advantage compared to control. In the trial currently being planned by the US Gas- subsequent studies, throughout the 1990s, various investigative groups conducted trials comparing trointestinal Intergroup will compare 5-FU, leu- various different schedules and combinations covorin and irinotecan to 5-FU, leucovorin and of 5-FU combined with either leucovorin or oxaliplatin. None of these trials demonstrated a realities of conducting trials in the adjuvant colon statistically signiﬁcant improvement in survival setting – namely, that patient outcome has been between study arms, although through such trials sufﬁciently improved that signiﬁcant follow-up it did become clear that 6 months of 5-FU plus is required in order to obtain sufﬁcient events to leucovorin was at least as effective as 12 months power a study. The options for of 2002) for stage 3 colon cancer is 6 months of conducting a follow-up study are thus to wait at 5-FU plus leucovorin. A dis- the delivery of 5-FU as a short-term bolus cussion of the second area, tailoring therapy to 126 TEXTBOOK OF CLINICAL TRIALS the individual patient, will be deferred until the Mamounas et al. In none One additional insight into the conduct of clin- of these four trials was there a direct randomised ical trials in GI cancers may be gained by exam- comparison between treatment and control. In ining the steady increase in the sample sizes that their analysis, the authors estimated the magni- has occurred in stage 3 colon clinical trials over tude of the difference in outcome between the two the past two decades. They then early 1980s, sample sizes of 100–200 per arm compared whether this difference in outcome dif- were typical,48,52 with some exceptions (such as fered by patient stage. The authors concluded that the NSABP C-01 trial, with approximately 380 the treatment effect within each study was similar patients per arm). Fortunately, 5-FU, when ment is beneﬁcial in stage 3 patients, they con- combined with either levamisole or leucovorin, cluded that treatment is also beneﬁcial in stage did provide a rather large effect, with a reduction 2 patients. In this analysis, the study team pooled ment advance by such a magnitude is unlikely, the data from stage 2 patients who had partic- and smaller advances may indeed be clinically ipated in ﬁve randomised trials of 5-FU plus relevant. They found no statis- disease have included sample sizes of 1600 (trial tically signiﬁcant beneﬁt of treatment, based on C89803), 2400 (trial C-06) and 4900 patients for a pooled sample size of just over 1000 patients. One possible strategy for prac- had poor power to detect a small but possi- tically conducting such large trials is discussed in bly important improvement in patient outcome the next section. Thus, the beneﬁt of 3 disease, the beneﬁt of adjuvant treatment for 5-FU based adjuvant therapy in stage 2 disease stage 2 (node negative) disease is unclear. In remains unclear, and further pooled analyses will many previous trials, patients with stage 2 disease likely be necessary. A large randomised trial of have been pooled together with stage 3 patients. For a variety of reasons, patients trial should help clarify the appropriate treatment with stage 3 disease have typically constituted for patients with stage 2 disease. Due to the limited sample size in It is likely that more clinical trials have been each trial, two attempts have been made to pool conducted in advanced colon cancer than in any data from several trials in order to gain a sufﬁ- other GI disease site.
The use of non-standard instru- matic trials are needed initially to convince peo- ments to measure awareness of stigma discount atorlip-20 20 mg with mastercard, coping ple that therapy is worthwhile discount 20mg atorlip-20 free shipping. What needs to be deﬁned for trials positive and negative symptoms at post-treatment of CBT for psychosis is the clinical signiﬁcance and follow-up in some studies safe atorlip-20 20mg. This was alluded to earlier in this als that have been designed to test the speciﬁcity chapter. Clinically signiﬁcant outcomes may be of treatment have not been so successful. Very reductions in the distress associated with the few differences emerge between CBT for psy- disorder. Currently clinical signiﬁcance is deﬁned chosis and alternative therapies are shown at post- as the sorts of improvements that are achieved treatment. Of the two studies with long follow- in drug trials–20% change in symptoms. This ups one showed an advantage for CBT over the alternative therapy16 but the other showed equiv- may be a low threshold for what could be achieved through psychological therapy. Many alent beneﬁts of both therapies (CBT and sup- trials of psychological therapy adopt only a portive counselling) over routine care. However, the effects only by these later developments that it will be of this therapy were not sustained to a follow-up possible to develop training and therefore provide where the patients in the comparison therapy con- larger numbers of people with psychosis with dition actually got worse. Nat- ural course of schizophrenic disorders: a 15 year ing symptoms over the course of the therapy and follow-up of a Dutch incidence cohort. Recent Advances in the counselling framework may be either shared Understanding Mental Illness and Psychotic Expe- riences. Leicester: British Psychological Society with supportive counselling or are as effective (2000). Cognitive therapy ble that within the model of schizophrenia which for psychosis: formulation, treatment, effects and encompasses a vulnerability stress model that the service implications. J Mental Health (1998) 7: two forms of therapy may work via different 123–33. Supportive counselling may work by rah JS, Porceddu K, Watts S, Freeman HL. The emphasising self-esteem through rapport within community management of schizophrenia: a con- the therapeutic relationship. Unlike befriending trolled trial of a behavioural intervention with fam- this support produces more stable changes that ilies. Cunningham-Owens DG, Carroll A, Fattah S, Clyde Z, Coffey I, Johnstone EC. A randomised, noted that supportive counselling did signiﬁcantly controlled trial of a brief educational package worse at treating hallucinations when compared for schizophrenic outpatients. Successful outpatient psychotherapy behaviour therapy works via a cognitive system, with a schizophrenic with delusion based on borrowed guilt. There may be many idiosyncratic routes behaviour therapy in the treatment of schizophre- that will only be established in large trials with nia: a review. Tarrier N, Beckett R, Harwood S, Baker A, In this trial hundreds of acute patients who are at Yusupoff L, Ugarteburu I. A trial of two cognitive behavioural methods of treating drug-resistant the beginning of their illness have been provided residual psychotic symptoms in schizophrenic with therapy and followed up over a long period. Br J Psychiat (1993) 162: It is only through these sorts of studies that it 524–32. Garety P, Kuipers E, Fowler D, Chamberlain F, empirically, all must have prizes. Drury V, Birchwood M, Cochrane R, Macmil- ison of cognitive therapy, applied relaxation and lan F. Cognitive therapy and recovery from acute imipramine in the treatment of panic disorder.
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