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I can only hope they will be put under scrutiny and substantiated or refuted by others order doxazosin with american express gastritis diet and recipes. A good example of such problems lies in the use of informed consent for elective procedures purchase 4mg doxazosin overnight delivery gastritis diet ��. Informed consent obtained by the physician who will do the elective procedure is probably not truly informed consent best 1mg doxazosin gastritis otc. I am so certain of this concern that I suggest that someone not doing or involved in the procedure should obtain the consent of the patient. The extreme variation in the rate of procedures across small geographic areas also suggests that some factor other than clinical need is operating (see Wen- nberg and Gittelsohn 1982). At the very least, to test these ideas, the profession should carefully study video-recorded examples of physicians obtaining informed consent. Several foun- dations said we provided no basis for our suggested studies. I have often wondered if behavioral studies of the sort we suggested were simply outside the prevailing biomolecular model and therefore not fundable. I had returned to Vanderbilt and Saint Tomas from my sabbatical in Fairhope, even more determined to explore and deﬁne the prob- lems of patients with SUO. An extensive GI workup by her referring physician, including a small-bowel biopsy, was entirely normal. Every test I might consider had already been done, with negative ﬁndings. The results of the workup ruled out a long list of diseases, but it did not establish a diagnosis. Agnes had noted no pattern to the diarrhea and thought it came all the time. Embedding challenges in questions reduces the chance of a defensive answer. People hear embedded challenges as less confrontational than direct challenges. The trick is to get the patient to ﬁnd and deﬁne that wobble, that variance. Insistence by a patient that 102 The Diarrhea of Agnes 103 any chronic symptom is continuous or all the time is a red ﬂag. By challenging Agnes, I was setting in motion a search for the pattern of the diarrhea. She did not know her pattern of diarrhea on the early visits and would have to discover it. I had found my approach of refusing to label patients prema- turely more and more useful and productive. I was careful to name those diseases that had killed some member of the family if I was sure the patient did not have that disease. My reasoning was that whatever buried anxiety patients might have had over the family killer might be reduced by speciﬁcally telling them the disease was not present. In some cases, I suspected that the anxiety and worry over inheriting a family disease were suﬃcient in themselves to produce the symp- toms. My statement at least got the subject out in the open in a subtle manner. With Agnes, as with other patients, I wanted to avoid using what I call dead-end diagnoses. Without exhaustive examinations for causes, these labels are prematurely deﬁnitive. Something, usu- ally something ingested, is causing the bowel to be irritable or the colon to be spastic. Tere was no mention of time or 104 Symptoms of Unknown Origin place or context, yet both questions clearly directed the patient to do an exhaustive mental search. I was directing the patient to search for an answer, but I was not specifying in any way what area of life was to be scanned. In the ﬁrst question, I left open all possibilities for what actions the patient could stop doing. Tese directed but unspeciﬁed injunctions cre- ate maximum internal mental searches for answers. Tere is a certain elegance in using a process approach such as this and staying out of content. As long as the process leads to corrective action, I do not need to know the con- tent. This approach also permits the patient to ﬁnd or admit to hidden perverse or abhorrent be- haviors without discussing them. This powerful technique clearly pushes the patient to ﬁnd solutions, as speciﬁed and direct questions do not. I was also becoming more aware of the timing of my words and the inﬂections of my voice. In both these questions, I emphasize certain short phrases with my tone: What are you doing that you should stop doing? I supposed the brain would hear this as stop doing whatever it had sorted out to be stopped. For the second question, I emphasize with my tone of voice and volume should be doing, making this an injunction for the patient to dis- The Diarrhea of Agnes 105 cover what action might be missing. Either question could produce deep thought with slackened facial muscles and sometimes a drooping of the mouth. I waited as long as necessary until the patient shifted to a more alert facial expres- sion. My intention was to leave the door open to all possibilities by being directive but not speciﬁc. I wanted the patient to supply the speciﬁcity from his or her own thoughts and observations, not from mine. If I asked speciﬁc questions, the patient could only af- ﬁrm or deny them. I am literally guessing when I ask narrow questions, and guessing can go on ad inﬁnitum. However, if I ask the question more broadly—Do you ever have any pains? Tus, if I ask general nonspeciﬁed questions, the patient must supply the detail. With Agnes, in addition to the two unspeciﬁed questions, I asked her to note in a diary the time and place of each bowel move- ment and the associations that came to mind.

If neural truncal and leg activity for locomotion (see repair strategies are to produce functional ben- Chapter 1) generic doxazosin 2 mg with visa gastritis diet 3-2-1. Segmental sensory feedback from efits to patients cheap 2 mg doxazosin with mastercard gastritis diet ��, biologic interventions will re- locomotor-related proprioceptive and cuta- quire motor learning and rehabilitation inter- neous afferents has a powerful modulating ef- ventions to help train the new networks purchase doxazosin mastercard gastritis empty stomach. Cortical rep- cilitation may lead to functional incorporation resentations for the hand and trunk have shown of new motoneurons and ascending and de- considerable plasticity in people with complete scending axons that bridge a SCI. Repetitive from altered spinothalamic and spinocerebel- practice under a variety of conditions may in- lar inputs to primary motor cortex. The spino- duce many of the neurochemical, trophic, and cerebellar pathway runs along the outer rim of morphologic changes in the spinal cord that spinal cord white matter, so it may be partially underpin proposed neural repair strategies. These experiments are OF REPAIR TO CLINICAL TRIALS often given a breathless sound byte by the me- dia, which raises expectations about an immi- the number of failed phase 2 and phase 3 hu- nent cure for paralysis. Clinicians often express rodent models of injury,320–324 as of the year the misconception that basic research with an- 2002, at least 65 randomized clinical trials in imals is easier to carry out, more scientifically stroke, 25 in cerebral trauma, and 8 in SCI have rigorous, and permits the measurement of not led to better outcomes for patients. Only more clearcut outcomes than any possible de- one or two acute interventions for each type of sign for a clinical trial in patients. Investigators ventional studies in animal models have sys- and pharmaceutical companies have tried to tematic flaws that may mislead clinicians about find ways to explain the failures to translate ro- the potential for efficacy in human trials? Overview of Animal Models of Neural Repair for Spinal Cord Injury MODELS Rodents Standard drop weight contusion Focal demyelination Focal compression Root avulsion Hemisection—dorsal or lateral cord Transgenic mouse gene manipulation Tract ablation Nonhuman primates Tract ablation Root avulsion MEASURED OUTCOMES Gross tissue preservation Histology Label and count new axons, growth cones, boutons Morris water maze Label and count new neurons Activity meter Behaviors (often videotaped evaluations) Robotic device measures—kinematics, torques Forepaw use—feeding, locomotion, climbing Sensation—tail flick analgesia Hindlimb use—BBB scale for qualitative locomotion; footprint placement; grid, beam or ladder walk BBB, open-field Basso, Beattie, Bresnahan score. Also, microstimulation of the motor cortex that represents the paw and 1. In animal re- distal arm reveals a much smaller representa- search, vendors provide healthy, highly inbred tion for the wrist in Fischer rats than in Long- rats and mice. Intensive training of paw reaching and strain, same age, weight, and gender. The CNS of a gle gene mutation permits the study of a spe- neonate may still be developing, allowing for cific phenotype, such as absence of an in- far greater opportunity for morphologic adap- hibitory molecule in the matrix of the cord or tations than may evolve in an adult. In human excessive production of a particular neu- trials, the study population has great variabil- rotrophin. Different inbred murine strains re- ity in genes, age, sex, medication taken, and spond quite differently to ischemia or trauma premorbid health. Such heterogeneity in hu- and most mice respond differently than most mans may not be overcome by simply using rats in terms of injury and regenerative cas- large sample sizes and some obvious inclusion cades. Indeed, large sample sizes will not be cannot assume that a human subject will have practical for trials of neural repair strategies. Even in rats, significant interspecies and in- Laboratory rodents are kept in separate trastrain variablity may foil the results of stud- cages in most instances, so they do not injure ies carried out in different laboratories. Although the rodents animals depend largely upon rules that evolved came from the same strain, different vendors from interactions with natural environments. Indeed, although highly in- than others to develop a glial scar after the bred transgenic mice are wonderful tools for same SCI that produces a large barrier to ax- the study of the effects of specific genes, envi- onal regeneration in another species. Differ- ronmental conditions have led to a reversal of ences in injury-induced T-cell responses and in those gene effects. The biologic effects of an in- Biologic Adaptations and Neural Repair 131 tervention and its behavioral outcomes have, produce a uniform lesion with particular fea- for example, been repeatedly confounded by tures that represent a partial equivalent to hu- differences in caloric intake, whether sponta- man damage, the model may not serve a study neous or secondary to the experimental of repair. Some injury models originally aimed to search for repair mechanisms may yield results evaluate NMDA receptor-mediated neuronal in rats that are not clearly relevant to people. Most hu- For example, I discussed trials in which run- man lesions from stroke or TBI do not even ning in an enriched environment increased involve the hippocampus, unless global hypo- production of a variety of neurotrophins, as perfusion or hypoxia develop. The AMPA recep- ural environments evolved to find food and tors of oligodendrocytes mediate cytotoxic in- shelter by scurrying about as they vigilently at- jury, not NMDA receptors. Aimless tions across tissues help account for the failure exercise, such as jogging on a treadmill or wan- of human clinical trials of interventions for dering in a shopping mall, may be much less NMDA receptor-mediated injury. Differences of an inducement for the stimulation of BDNF in receptor types within regions of the brain and other growth factors, genes that promote and spinal cord and further changes brought plasticity, memory molecules, or neurons in pa- on by injury will also have to be reckoned with tients with neurologic diseases. If such stimu- in the translation of models to human neural lation is part and parcel to human learning, as repair. Among other queries, the reader of an it seems, learning paradigms will need to be experiment carried out with animals or cell cul- designed for rehabilitation that stimulate genes tures must always wonder how similar the re- and cells. Is the model of injury and repair in ro- had been used and how applicable the partic- dents similar enough to what happens to peo- ular model of injury and repair will be to the ple? Scooping out cortex in an ablation model majority of clinical injuries and of mechanisms for stroke may produce the same amount of tis- of restitution or substitution. Is the brain and spinal cord of a rat or cade of molecules and gene expression that fol- mouse simply a thimble-sized version of the hu- low injury will differ between ablation and man brain? The surface area of the brain of a ischemia, as described in Experimental Case mouse is 1/1000th that of the human brain. The milieu for mechanisms of re- Studies of axonal regeneration in rats and mice pair will differ as well with the type of lesion consider an extension of axons for a few mil- induced. A cortical infarct will not elicit the limeters to a centimeter as exuberant growth. Axons in human brain to moderate cortical injury that resolves in sev- or spinal cord may have to grow from several eral days. A human injury may include contu- centimeters to over a meter to reach targets. These differences in pathology and the Signaling molecules that fashioned the CNS persistence of injury-induced cascades in hu- during embryogenesis and development never mans make interventions for neuroprotection had to manage such long distance tours. Very different fective dose-response curve for biologic inter- mechanisms and outcomes may unfold in hu- ventions in man? A repair intervention in mice mans over time as molecular cascades interact. Since humans will need to produce complex behav- the injury model was originally developed to iors such as goal-directed walking and manip- 132 Neuroscientific Foundations for Rehabilitation pair intervention in the rat or mouse and the timing of the same intervention in patients? Medications may have con- founding effects on an intervention for repair. The need for immunosuppressants after a transplant of cells may have adverse effects on regenerative capacity. In addition, animals do not take drugs for hypertension, diabetes, pain, seizures, and other ailments. How will adjunct drugs and associated diseases affect the human equivalent of an animal intervention, especially over the weeks and months needed for some types of repair? Adjuncts may alter the ab- sorption or metabolism or bioavailability of the experimental intervention. Also, an interven- tion in a rodent model is derived from dose- response curves for serious toxicity such as death. Human trials almost invari- man brain compared to a whole brain and spinal cord from ably use doses of drugs that are far lower than a rat and the even smaller CNS of a mouse.

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Similareffects(andabsenceofeffectsinsoleus)have beenobtainedfromstimulationofvariousskinﬁelds Effects of low-threshold cutaneous on the foot sole buy doxazosin 1mg online gastritis diet ��. The time course of the cutaneous afferents effects when the ISI between cutaneous and con- ditioning group I volleys was varied shows an early In the low spinal cat purchase doxazosin with visa gastritis que puedo comer, the dominant effect of cuta- suppression lasting for a few milliseconds followed neous afferents is disynaptic facilitation of interneu- byfacilitation-MACROS-. Calculationsbased rones conveying Ib inhibition (Lundberg discount doxazosin 4mg amex chronic gastritis mucosa, Malmgren on the distances from stimulation sites to the spinal & Schomburg, 1977). However, owing to the mutual cord and the afferent conduction times of the cuta- inhibition of these interneurones, trisynaptic cuta- neous and group I volleys suggest that the early sup- neous IPSPs may also be recorded in Ib interneu- pression is mediated through a short oligosynap- rones (see Brink et al. A possible circuit for the cutaneous suppression is sketched in the diagram in Fig. Itispresumed Cutaneous suppression of Ib inhibition that, at rest, in the absence of descending activity to knee muscles at rest (see below), cutaneous excitation is dominant on a Atrest,cutaneousvolleyscandepressIbinhibitionto subpopulation of interneurones, e. Cutaneous facilitation of transmission in reﬂex pathways from Ib afferents Cutaneous facilitation of homonymous Ib inhibition of quadriceps has been observed However, the most frequently observed effect of during strong contractions of quadriceps low-threshold cutaneous volleys is facilitation of transmission in the pathway of Ib inhibition to the facilitation of the quadriceps H reﬂex produced motoneurones. The inhibition Cutaneous facilitation at rest during contraction is the result of cutaneous facilita- Even at rest, cutaneous facilitation of Ib inhibition to tionofIbinhibitionactivatedbythetestvolleyforthe knee muscle motoneurones follows the initial cuta- quadriceps H reﬂex (Marchand-Pauvert et al. This effect is potent from gas- Such an inhibition of the quadriceps H reﬂex dur- trocnemius medialis to biceps and for homonymous ing quadriceps contraction has not been observed quadriceps group I inhibition (Pierrot-Deseilligny after stimulation of the sural nerve or of the foot et al. Cutaneous facilitation of gastrocnemius medialis-induced Ib inhibition during voluntary Cutaneous facilitation of transmission contractions of triceps surae in Ib pathways has also been observed in the upper limb Gastrocnemius medialis-induced Ib inhibition to soleus is decreased with respect to rest during the initial radial-induced inhibition of the FCR H gastrocnemius-soleus voluntary contractions (see reﬂex is curtailed by a trend to facilitation attributed pp. This cutaneous facil- lation in various situations, and this suggests that itation of gastrocnemius medialis-induced Ib inhi- interneurones transmitting Ib inhibition to a given bition to soleus and quadriceps has been disclosed motoneurone pool are organised in subpopulations, only when (i) the voluntary contraction involves the which may be differentially selected in different triceps surae, and (ii) the cutaneous stimulation is tasks, through descending control and mutual inhi- applied to the anterior part of the foot sole (grey area bitionofIbinterneurones. The effects of the triceps surae con- neous facilitation of Ib inhibition might be used to tractionprobablyresultfromdescendingfacilitation curtail an exploratory movement (see pp. Recurrent inhi- by joint afferents bition produced by the discharge of the unit could not suppress the discharge of that same unit, and So far, the effects of joint afferents have only been aRenshaw origin of the inhibition is unlikely. Gat- investigated on the pathways of Ib inhibition to ing of the femoral volley is therefore likely, and this is quadriceps motoneurones. Similar effects by joint afferents were observed with joint afferents from the ankle Conditioning stimulation can be applied to the lat- travelling in the deep peroneal nerve (Chapter 1, eral articular nerve of the knee joint, which con- pp. Stimulation of joint afferents facilitates the Facilitation of heteronymous Ib inhibition quadricepsHreﬂexduringweakquadricepscontrac- by joint afferents tions, but this can be reversed to inhibition during the effects of increased pressure in the knee joint strong contractions. However, during caused by intra-articular infusion of saline (indu- strong contractions, the same joint afferent volley cing no sensation of pain) have been investigated facilitates the on-going voluntary EMG recorded on the quadriceps H reﬂex (Iles, Stokes & Young, in the quadriceps at corresponding central delays 1990). The facilitation of the on-going EMG the quadriceps H reﬂex both at rest and during probably results from facilitation of motoneurones quadriceps contractions. Joint distension also pro- by joint afferents, as has been described in the cat duces spatial facilitation of Ib inhibition of the after rubral stimulation (Hongo, Jankowska & Lund- quadriceps H reﬂex from group I afferents in the berg, 1969; sketch in Fig. Inhibition of the H reﬂex can between the effects on the EMG and H reﬂex dur- therefore be attributed to facilitation by knee joint ing strong quadriceps contractions is explained by afferents of interneurones mediating Ib inhibition the existence of an inhibitory mechanism gating the to quadriceps motoneurones. Investigations per- formed on the PSTHs of single units have allowed Conclusions this mechanism to be deﬁned. This facilitation of Ib inhi- voluntarily active vastus lateralis unit was reduced bition could play a role in the relaxation of a mus- when it was preceded by an articular volley, which cle when joint afferents are activated in hyperﬂexion by itself did not modify the ﬁring probability of the or-extension(seep. The difference between the effect on com- interneurones by joint afferents could also have a bined stimulation and the sum of effects of separate protective role in preventing excessive contraction 264 Ib pathways Ib IN 8 (a) (d ) FN 0. Facilitation of autogenetic Ib inhibition of quadriceps by knee joint afferents. Ib and Ia afferents from quadriceps (Q) and knee joint afferents converge onto common Ib interneurones (INs) projecting onto Q motoneurones (MN). There is also a pathway mediating joint afferent excitation of MNs (revealed after rubral stimulation in the cat). Note the lack of suppression in the initial bins of the FN group I excitation (i. Organisation and pattern of connections 265 from damaging the ligaments and capsule of the Vestibular facilitation of Ib inhibition joint. The ﬁnding that the facilitation of autogenetic Spatialinteractionhasalsobeenfoundbetweengas- Ib inhibition of quadriceps motoneurones by knee trocnemius medialis-induced Ib inhibition and the joint afferents is seen only during strong quadriceps inhibition of the soleus H reﬂex evoked by galvanic contractions(cf. Here also, the inter- action is facilitatory when the inhibitions are weak, Effects from nociceptive afferents but reverses to occlusion when they are strong, pro- vidingevidenceforconvergenceofvestibularsignals Tonic activation of nociceptors has been shown onto interneurones mediating Ib inhibition. These changes increase in parallel interneurones with the sensation of pain. Opposite changes have been observed from the skin (dorsal surface of the In the above sections, multiple peripheral and foot) and muscle (extensor digitorum brevis): stimu- descendinginputshavebeenshowntoproducefacil- lationofnociceptivecutaneousafferentsincreasesIb itation or inhibition of interneurones mediating Ib inhibition, whereas stimulation of nociceptive mus- inhibition to motoneurones. The extent to which cle afferents decreases it (Rossi & Decchi, 1995, 1997; different inputs converge on the same subpopu- Rossi et al. Given that in the cat nociceptive lations of interneurones has been approached by afferentscanexciteandinhibitIbinterneurones(see activating Ib inhibitory interneurones to quadriceps Jankowska, 1992) and alter presynaptic inhibition of motoneurones by a femoral volley and combining Ia and Ib afferents (see Rudomin & Schmidt, 1999), this homonymous group I volley with various other the exact mechanism of these changes is difﬁcult to inputs. Descending effects Strong contractions Corticospinal excitation During strong contractions, cutaneous and joint Spatial interactions have been found between cor- afferents facilitate the transmission of homony- tically evoked and Ib inhibitions of the soleus H mous Ib inhibition of quadriceps motoneurones (cf. The reasons why convergence of femoral inhibitory actions are weak, the interaction is facil- groupIandjointorcutaneousvolleysisrevealedonly itatory, suggesting convergence onto interneurones during strong contractions of the target muscle are mediating Ib inhibition, as demonstrated in the cat discussed below. Increasing the strength of cortical and group I inhibitory actions During weak contractions of the quadriceps, invol- reverses the interaction, suppressing the inhibition. Ib and Ia afferents from quadriceps (Q) in the femoral nerve (FN), joint afferents in the deep peroneal (DPN) and cutaneous (Cut) afferents in the superﬁcial peroneal (SPN) nerves converge onto common Ib interneurones (INs) projecting onto Q motoneurones (MN). Pathways through which separate stimulation of DP and SP nerves evoke facilitation of Q MNs are not represented. Note the lack of suppression in the initial bins of the peak of femoral excitation (i. Motor tasks – physiological implications 267 Ia excitation evoked by femoral nerve stimulation elicited by combined deep and superﬁcial pero- in a voluntarily activated vastus lateralis unit was neal volleys in Fig. If anything, in the absence of the femoral group I volley, combined stimulation of deep and superﬁ- Conclusions: necessity for convergence cial nerves produced some facilitation in the PSTH of multiple inputs (not illustrated). This indicates that convergence of thetwoconditioningvolleyswiththefemoralgroupI the above ﬁndings indicate that group I afferents in volley is required for the inhibition to manifest itself. At rate stimuli (h)reveals a profound suppression that rest, or during weak contractions, this convergence spares the ﬁrst 0. This initial sparing conﬁrms the conver- articular and cutaneous, which excite Ib interneu- genceofthedifferentvolleysontointerneuronesthat rones through ﬁrst-order interneurones (see the areintercalatedinadisynapticinhibitorypathwayto sketch in Fig. The most parsimonious explanation would be gence has been observed when combining afferent that during such contractions there is a descend- volleys in the superﬁcial (or the deep) peroneal and ingfacilitationoftheﬁrst-orderinterneuronesmedi- the lateral articular nerve of the knee joint. Thus, descending voluntary drives would have two effects: (i) depression of transmis- Resting conditions sion in Ib inhibitory pathways, which would prevent At rest, stimulation of either the superﬁcial or the the Ib discharge from the contracting muscle from deep peroneal nerves at appropriate ISIs and inten- hinderingthedischargeofactivemotoneurones;and sities facilitates the quadriceps H reﬂex (Figs. Yet, when the two con- transmission through interneurones mediating this ditioningvolleyswerecombined,thefacilitationpro- Ibinhibition,thusallowingautogeneticinhibitionto duced by either volley alone was reversed to signiﬁ- reappear when necessary to modulate contractions cant suppression. Thus, suppression of the quadriceps Motor tasks and physiological Hreﬂex, due to convergence of conditioning volleys implications inbothdeepandsuperﬁcialperonealnerveswiththe femoral test volley may be observed at rest. The brief Human tendon organs respond readily in isometric duration of the inhibition of the quadriceps H reﬂex voluntary contractions and usually discharge 268 Ib pathways strongly during shortening contractions, even in rest, but this inhibition is markedly depressed dur- the absence of an external load.

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Ad- blood levels because they metabolize theophylline rapidly purchase doxazosin on line gastritis heartburn, ministration of activated charcoal and a cathartic is also and clients with liver disease buy cheap doxazosin 1 mg on-line gastritis diet ��, congestive heart failure buy 1mg doxazosin visa gastritis histology, recommended, especially for overdoses of sustained- chronic pulmonary disease, or acute viral infections usually release formulations. For obese clients, theophylline dosage the airway, giving oxygen, injecting IV diazepam (0. Toxicity of Antiasthmatic Drugs These drugs seem relatively devoid of serious toxicity. There have been few reports of toxicity in humans and Signs and symptoms of overdose and toxicity are probably little clinical experience in managing it. If toxicity oc- most likely to occur when clients with acute or chronic curs, general supportive and symptomatic treatment is bronchoconstrictive disorders overuse bronchodilators in indicated. Adrenal insufficiency is most likely to occur with sys- temic or high doses of inhaled corticosteroids. Dose-related Gwen, a 7th grader, comes to the health center at the middle school in moderate respiratory distress. Her respiratory rate is inhibition of growth has been reported in short and inter- 36 and you hear audible wheezing without a stethoscope. Her in- mediate studies but long-term studies have found few, if any, halers (albuterol and Vanceril) are kept in the health center for decreases in expected adult height. Gwen has not been in to use have not been associated with signiﬁcant decreases in bone her inhalers for the last week. Bone growth should be monitored might be important to assist Gwen in long-term management of closely in children taking corticosteroids. The risk of high doses is especially great in children with other allergic conditions that require topical Use in Children corticosteroid drugs. The risk can be decreased by using the lowest effective dose, administration techniques that mini- the American Academy of Pediatrics endorses the clinical mize swallowed drug, and other antiasthmatic drugs to re- practice guidelines established by the National Asthma duce corticosteroid dose. In gen- Leukotriene modiﬁers have not been extensively studied eral, antiasthmatic medications are used in children and in children and adolescents. With montelukast, the 10-mg adolescents for the same indications as for adults. With ﬁlm-coated tablet is recommended for adolescents 15 years adrenergic bronchodilators, recommendations for use vary of age and older and a 4-mg chewable tablet is recommended according to route of administration, age of the child, and for children 2 to 5 years of age. However, even infants and young zaﬁrlukast in children younger than 12 years have not been children can be treated effectively with aerosolized or neb- established. In addition, some oral drugs can be given to Cromolyn aerosol solution may be used in children 5 years children as young as 2 years and most can be given to chil- of age and older, and nebulizer solution is used with children dren 6 to 12 years of age. Nedocromil is not established as safe and With theophylline, use in children should be closely effective in children younger than 12 years of age. In children younger than 6 months, especially premature infants and neonates, drug elimination may be Use in Older Adults prolonged because of immature liver function. Except for pre- term infants with apnea, theophylline preparations are not Older adults often have chronic pulmonary disorders for which recommended for use in this age group. Children 6 months bronchodilators and antiasthmatic medications are used. As to 16 years of age, approximately, metabolize theophylline with other populations, administering the medications by in- more rapidly than younger or older clients. Thus, they may halation and giving the lowest effective dose decrease adverse need higher doses than adults in proportion to size and effects. If the child is obese, the dosage should be calculated excessive cardiac and CNS stimulation. On the one hand, cigarette forms are not recommended for children younger than smoking and drugs that stimulate drug-metabolizing en- 6 years of age. Children may become hyperactive and dis- zymes in the liver (eg, phenobarbital, phenytoin) increase ruptive from the CNS-stimulating effects of theophylline. On Tolerance to these effects usually develops with continued the other hand, impaired liver function, decreased blood ﬂow use of the drug. Adverse effects include cardiac and CNS stimula- ment of persistent bronchoconstrictive disorders. Safety can be increased by measuring serum drug tiveness and safety of inhaled corticosteroids in children older levels and adjusting dosage to maintain therapeutic levels than 3 years of age is well established; few data are available of 5 to 15 mcg/mL. If the client is obese, dosage should be on the use of inhaled drugs in those younger than 3 years. Most are Corticosteroids increase the risks of osteoporosis and given by inhalation, and dosage, type of inhaler device, and cataracts in older adults. Leukotriene modiﬁers usually are well CHAPTER 47 DRUGS FOR ASTHMA AND OTHER BRONCHOCONSTRICTIVE DISORDERS 711 tolerated by older adults, with pharmacokinetics and effects Use in Critical Illness similar to those in younger adults. With zaﬁrlukast, however, blood levels are higher and elimination is slower than in Acute, severe asthma (status asthmaticus) is characterized by younger adults. Zileuton is contraindicated in older adults with severe respiratory distress and requires emergency treatment. Beta2 agonists should be given in high doses and as often as every 20 minutes for 1 to 2 hours (by MDIs with spacer devices or by compressed-air nebulization). However, high doses of nebulized albuterol have been associated with tachycardia, Use in Renal Impairment hypokalemia, and hyperglycemia. Once symptoms are con- trolled, dosage can usually be reduced and dosing intervals ex- Bronchodilating and anti-inflammatory drugs can usually tended. High doses of systemic corticosteroids are also given be given without dosage adjustments in clients with im- for several days, IV or orally. Beta agonists may be given by in- drug, there is no therapeutic advantage to IV administration. Theophylline can be given in When respiratory function improves, efforts to prevent fu- usual doses, but serum drug levels should be monitored. Cromolyn is eliminated by renal and biliary excretion; the drug should be given in reduced doses, if at all, in clients with Home Care renal impairment. All of the drugs discussed in this chapter are used in the home setting. A major role of the home care nurse is to assist clients in using the drugs safely and effectively. Several studies have Use in Hepatic Impairment indicated that many people do not use MDIs and other in- Montelukast and zaﬁrlukast produce higher blood levels and halation devices correctly. The home care nurse needs to ob- are eliminated more slowly in clients with hepatic impair- serve a client using an inhalation device when possible. However, no dosage adjustment is recommended for errors in technique are assessed, teaching or reteaching may clients with mild to moderate hepatic impairment. With inhaled medications, a spacer device may be associated with hepatotoxicity and contraindicated in clients useful, especially for children and older adults, because less with active liver disease or aminotransferase elevations of muscle coordination is required to administer a dose. In addition, assist clients to recognize every 2 to 3 months for the remainder of the first year, and and treat (or get help for) exacerbations before respiratory periodically thereafter. In addition, the nurse needs to Cromolyn is eliminated by renal and biliary excretion; the reinforce the importance of not exceeding the prescribed drug should be given in reduced doses, if at all, in clients with dose, not crushing long-acting formulations, reporting adverse hepatic impairment.

Etanercept is approved for clients 4 to She complains of general malaise and not feeling well for the past 17 years of age with juvenile rheumatoid arthritis buy doxazosin 4mg fast delivery gastritis diet nuts. What additional in- trials proven doxazosin 4 mg antral gastritis definition, effects in children were similar to those in adults proven 1 mg doxazosin gastritis diet kits. Most formation will you collect to differentiate between infection and children in a 3-month study had an infection while receiving organ rejection? The infections were usually mild and consistent CHAPTER 45 IMMUNOSUPPRESSANTS 685 with those commonly seen in outpatient pediatric settings. Other medications (eg, a cor- of accumulation to toxic levels and additional renal ticosteroid, methotrexate, a nonsteroidal anti-inﬂammatory damage. However, the risks are less with the small drug, or an analgesic) may be continued during treatment. To de- crease these risks, adequate renal function should be Use in Older Adults documented before the drug is given and clients should be well hydrated. Immunosuppressants are used for the same purposes and pro- • Muromonab-CD3 has caused increased serum creati- duce similar therapeutic and adverse effects in older adults as nine and decreased urine output in a few clients during in younger adults. This was attributed to the re- disorders and organ impairments, it is especially important that lease of cytokines with resultant renal function impair- drug choices, dosages, and monitoring tests are individualized. The renal In addition, infections occur more commonly in older adults, function impairment was reversible. Overall, there is lit- and this tendency may be increased with immunosuppressant tle information about the use of this drug in clients with therapy. Doses higher than 1 g twice a • Azathioprine metabolites are excreted in urine but they day should be avoided in these clients. There is no in- are inactive, and the dose does not need to be reduced in formation about mycophenolate use in cardiac trans- clients with renal impairment. Dosage does not need to be re- has been noted in 25% of renal, 38% of cardiac, and duced with renal impairment. It usually subsides with decreased dosage or toxicity when given IV, so oral dosing is preferred. In renal transplant recipients, when serum creatinine and blood urea nitrogen levels remain elevated, a com- Little information is available about the use of basilix- plete evaluation of the client must be done to differen- imab, etanercept, inﬂiximab, or leﬂunomide in clients with tiate cyclosporine-induced nephrotoxicity from a renal impairment. However, leﬂunomide metabolites are partly transplant rejection reaction (although up to 20% of excreted renally and the drug should be used cautiously. If dosage reduction does not improve renal function, another im- munosuppressant is preferred. Use in Hepatic Impairment If renal function is deteriorating from a rejection re- action, decreasing cyclosporine dosage would increase • Azathioprine is normally metabolized to its active the severity of the reaction. As a result, pharmacologic ac- does not respond to treatment with corticosteroids and tion is decreased in clients with hepatic impairment. Liver To decrease risks of nephrotoxicity, dosage is ad- function usually improves within a week if azathioprine justed according to cyclosporine blood levels and renal is discontinued. An additional factor is the potential for vated serum aminotransferases and bilirubin) in ap- signiﬁcant drug interactions with microsomal enzyme proximately 4% of renal and liver transplant recipients inhibitors and inducers. This is most metabolism (eg, cimetidine) raise cyclosporine blood likely to occur during the ﬁrst month of therapy, when levels, whereas those that stimulate metabolism decrease high doses of cyclosporine are usually given, and usu- levels. With liver im- cate that these clients eventually sustain liver changes pairment, less formation of the active metabolite may that may include fatty deposits, lobular necrosis, ﬁbro- result in reduced therapeutic effect. The active metabolite is further metabolized and ex- to the deposition of methotrexate and its metabolites in creted through the kidneys and biliary tract. Many clinicians recommend serial liver the drug excreted in bile is reabsorbed. The role of the liver in drug metabolism and excretion in cause fibrosis and cirrhosis may not produce clinical bile increases risks of hepatotoxicity. In addition, in clients with or without initial liver im- Most elevations were mild and usually subsided with pairment, liver function tests should be performed to continued therapy. Higher elevations were infrequent monitor clients for hepatotoxicity and to guide drug and subsided if dosage was reduced or the drug was dis- dosage. It is recommended that liver enzymes, espe- creased by 25% if bilirubin (normal = 0. When ALT elevation is more than twice the upper the drug should be omitted if bilirubin is above 5 mg/dL. If ALT levels are more than twice but transferase [ALT]) with the ﬁrst few doses. Overall, not more than three times the ULN and persist despite however, there is little information about drug effects or dosage reduction, liver biopsy is recommended if use in clients with liver impairment. If elevations are more • Mycophenolate is metabolized in the liver to an active than three times the ULN and persist despite dosage metabolite that is further metabolized to inactive metabo- reduction and cholestyramine (see later), leflunomide lites. Liver impairment presumably could interfere with should be discontinued. ALT levels should be moni- these processes and affect both action and elimination. When leﬂunomide is stopped, a special procedure is clients with hepatic impairment. The procedure involves ad- may accumulate in the presence of hepatic impairment. If plasma levels are still above the goal level somal P450 enzyme system. Also, the elimination half-life is signiﬁcantly longer for IV or oral drug. As a result, dosage must be decreased in clients Home Care with impaired liver function. An additional factor is the potential for signiﬁcant With clients who are taking immunosuppressant drugs, a drug interactions with microsomal enzyme inhibitors major role of the home care nurse is to assess the environment and inducers. Leflunomide may be hepatotoxic in clients with infections, caregivers, water or soil around live plants, and normal liver function and is not recommended for use in raw fruits and vegetables. Meticulous environmental cleans- clients with liver impairment or positive serology tests for ing, personal hygiene, and hand washing are required. Considerations and guidelines include the dition, the nurse may need to assist with clinic visits for following: monitoring and follow-up care. CHAPTER 45 IMMUNOSUPPRESSANTS 687 NURSING Immunosuppressants ACTIONS NURSING ACTIONS RATIONALE/EXPLANATION 1. Give oral azathioprine in divided doses, after meals; give To decrease nausea and vomiting with oral drug IV drug by infusion, usually over 30 to 60 min. With basiliximab, infuse through a peripheral or central vein the ﬁrst dose is given within 2 h before transplantation surgery over 20–30 min. Use the reconstituted solution within 4 h at and the second dose 4 d after transplantation. IV drug is given to patients who are unable to take it orally; resume oral administration when feasible.

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