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Purine Analogues The plasma half-life of an intravenous bolus injec- Thioguanine (6-Thioguanine) tion of mercaptopurine is 21 minutes in children and 47 minutes in adults acne on back order decadron 0.5 mg. After oral administration acne cyst removal purchase 8 mg decadron with mastercard, peak Thioguanine is an analogue of the natural purine gua- plasma levels are attained within 2 hours skin care not tested on animals buy decadron online from canada. The drug is nine in which a hydroxyl group has been replaced by a 20% bound to plasma proteins and does not enter the sulfhydryl group in the 6-position. Xanthine oxidase is the primary enzyme involved nisms of cytotoxicity have been proposed for 6-thiogua- in the metabolic inactivation of mercaptopurine. Unlike most antimetabolites, it is toxic to nonpro- bine is thought to be a reflection of their ability to acti- liferating as well as dividing cells, primarily lymphocytes vate the drug more rapidly (by kinases) than to inacti- and lymphoid cancer cells. The drug is highly active in the treatment of chronic Cytarabine is rapidly metabolized in the liver, kid- lymphocytic leukemia, with approximately 40% of pa- ney, intestinal mucosa, and red blood cells and has a tients achieving remissions after previous therapy with half-life in plasma of only 10 minutes after intravenous alkylating agents has failed. About 80% of a given contributes to fevers and infections in as many as half of dose is excreted in the urine within 24 hours, with less treated patients. When the drug is given by continuous infusion, doses, with agitation, confusion, and visual disturbances. Pentostatin Cytarabine is used in the chemotherapy of acute myelogenous leukemia, usually in combination with an Pentostatin (Nipent, deoxycoformycin) is a purine iso- anthracycline agent, thioguanine, or both. It is less use- lated from fermentation cultures of the microbe ful in acute lymphoblastic leukemia and the lymphomas Streptomyces antibioticus. Intrathecal administration occasionally pro- leukemia, producing remissions in 80 to 90% of patients duces arachnoiditis or more severe neurological toxicity. Fluorouracil (5-fluorouracil, 5-fluorouracil, Efudex, Cladribine Adrucil) is a halogenated pyrimidine analogue that must be activated metabolically. Like the other purine Fluorouracil is selectively toxic to proliferating rather antimetabolites, it is relatively selective for both normal than non-proliferating cells and is active in both the G - 1 and malignant lymphoid cells and kills resting as well as and S-phases. The target enzyme inhibited by 5-fluo- dividing cells by mechanisms that are not completely rouracilfluorouracil is thymidylate synthetase, which understood. Less than 20% of the parent though cytotoxicity also occurs in other phases of the compound is excreted into the urine, the rest being cell cycle. In addition to the intercalation mechanism de- 5-Fluorouracil is used in several combination regi- scribed, the anthracycline ring of doxorubicin can un- mens in the treatment of breast cancer. It also has pal- dergo a one-electron reduction to form free radicals liative activity in gastrointestinal adenocarcinomas, in- and participate in further electron transfer. These highly cluding those originating in the stomach, pancreas, liver, active substances can then react with tissue macromol- colon, and rectum. This type of interaction suggests an alternative mor effects have been reported include carcinomas of mechanism of cytotoxicity for the anthracyclines. It has similar pharmacological effects but is pre- high degree of cross-resistance among the anthracy- ferred to 5-fluorouracil for hepatic arterial infusions be- clines, vinca alkaloids, dactinomycin, and podophyllo- cause it is more extensively metabolized in the liver toxins (see Chapter 55). Doxorubicin is not absorbed orally, and because of The toxicities of 5-fluorouracil vary with the sched- its ability to cause tissue necrosis must not be injected ule and mode of administration. Daily injection or continuous infusion is most is extensively metabolized in the liver to hydroxylated likely to produce oral mucositis, pharyngitis, diarrhea, and conjugated metabolites and to aglycones that are and alopecia. Neurological toxic- in the treatment of carcinomas of the breast, ovary, en- ity is manifested as acute cerebellar ataxia that may oc- dometrium, bladder, and thyroid and in oat cell cancer cur within a few days of beginning treatment. Some activity has been reported in Doxorubicin and Daunorubicin non–oat cell lung cancer, multiple myeloma, and adeno- The anthracycline antibiotics are fermentation products carcinomas of the stomach, prostate, and testis. Daunorubicin (Cerubidine) The most important toxicities caused by doxoru- is used to treat acute leukemias, while its structural ana- bicin involve the heart and bone marrow. Acutely, doxo- logue, doxorubicin (Adriamycin) is extensively em- rubicin may cause transient cardiac arrhythmias and ployed against a broad spectrum of cancers. Doxorubicin may 56 Antineoplastic Agents 647 cause radiation recall reactions, with flare-ups of der- A potentially fatal lung toxicity occurs in 10 to 20% matitis, stomatitis, or esophagitis that had been pro- of patients receiving bleomycin.

His assessment in the emergency Neck/Lymph Nodes department revealed him to have labored breathing that was more Soft acne vulgaris icd 10 cheap decadron amex, supple acne 6 days after ovulation buy decadron 8 mg online, no cervical lymphadenopathy difficult with activities acne nose generic decadron 8 mg visa. His other vital signs were a heart rate of 137 Chest beats per minute, blood pressure of 100/68, temperature of 38. What clinical parameters are necessary to evaluate the efficacy Neuro of the patient’s asthma therapy after hospital discharge? What methods could be used to help a pediatric patient and the Patchy infiltrates throughout lung fields family to be compliant with nebulization treatments? What information can be given to families who are concerned í Assessment about giving their child “steroids” for asthma treatment (either Asthma exacerbation with pneumonia and dehydration in an acute asthma exacerbation or for controller therapy)? Research the efficacy of systemic corticosteroids for treatment of acute asthma exacerbation when given intravenously versus oral- Problem Identification ly (enterally). What information (signs, symptoms, laboratory values) indi- you would refer a patient (or family) to the physician or cates the severity of the acute asthma attack? For proper treatment of an acute asthma exacerbation, the patient (or family) needs to be aware of the first symptoms of an exacerbation and 3. This in turn, should Optimal Plan decrease the number of severe exacerbations and hospital admissions. What drug, dosage form, dose, schedule, and duration of therapy are best for this patient’s acute asthma exacerbation? National Asthma Education and Prevention Program Expert Panel Report 3: Guidelines for the Diagnosis and Management of Asthma. Asthma exacerbations 5: assessment and of the acute exacerbation, Peyton was stable enough to transfer to management of severe asthma in adults in hospital. Levalbuterol versus 2 that he is more like his normal self and doesn’t seem to have much racemic albuterol in the treatment of acute exacerbation of asthma in trouble breathing now. What drug, dosage form, dose, schedule and duration of children and adults with acute asthma: a systematic review with meta- therapy are best for this patient’s discharge plan? Once the patient has transferred to the general medical floor respiratory tract infections in children with asthma. Budesonide inhalation suspension: a nebulized corti- therapy for achievement of the desired therapeutic outcome costeroid for persistent asthma. Anxious-appearing Caucasian female; moderate respiratory distress with audible wheezing noted; unable to speak in complete sen- • Identify potential causes of uncontrolled asthma. She states that she has been using her albuterol every hour for the past 6 hours and that it Nontender without masses doesn’t seem to be helping. She states she especially becomes short of breath when she exercises; although she admits that Deferred her shortness of breath is not always brought on by exercise and sometimes occurs when she is not actively exercising. She was also given nystatin swish and play a role in the development of asthma symptoms in such patients, swallow for treatment of her oral thrush infection. On follow-up at as inhibition of cyclooxygenase by aspirin may shunt the arachidonic day 4 in the clinic, her lungs are clear without wheezing; her respira- acid pathway away from prostaglandin synthesis and toward leuko- tory rate is 16 breaths per minute; and her pulse oximetry is 97% on triene production. What factors may have contributed to this patient’s poorly of Health, National Heart, Lung, and Blood Institute, Full Report 2007. Added salmeterol versus high-dose corticosteroid in asthma patients with symptoms on existing Desired Outcome inhaled corticosteroid. Low-dose fluticasone propionate compared with montelukast for first-line treatment of persistent asthma: a Therapeutic Alternatives randomized clinical trial. What nonpharmacologic therapies might be useful for this and oral zafirlukast in patients with asthma. Outline an optimal plan of treatment for this patient’s chronic (marketed as Xolair) information 2/2007. What clinical parameters are necessary to evaluate the therapy for 25 achievement of the desired therapeutic effect and to detect or prevent adverse effects?

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Some of the fibers penetrate the inferior tha- The cortical projections to the amygdala originate lamic peduncle to terminate in the dorsomedial nu- from the anterior cingulate gyrus (area 24) and cleus of the thalamus (Nauta 1969; Porrino et al acne 4 weeks pregnant buy generic decadron 4 mg on-line. Efferent fibers arising from most of the nate from the frontal lobe acne out biotrade purchase 1mg decadron fast delivery, the medial prefrontal (ar- amygdaloid nuclei course via both tracts (Amaral et eas 11 and 12) and the caudal orbitofrontal cortex al acne brand order decadron 8 mg fast delivery. Recent data (area 13 and 14), and from the temporal lobe, mainly from primates show that the amygdaloid nuclear the auditory (area 22), the visual associative (areas complex is also connected with the neocortex via the 20 and 21), the temporal polar (area 38), and from internal capsule. All wide cortical Afferent fibers to the amygdaloid nuclear com- areas project to the central nucleus. In view of these fear and defensive reactions, the intensity of the connections, the amygdala may be considered as an stimulus determining the level of the behavioral ag- important relay center through which external in- onistic response (Davis 1992; Gloor 1960). Complete puts may modulate the emotional state (Aggleton interruption of the ventral amygdalofugal pathway 172 Chapter 6 suppresses defense reaction. The effect of bilateral lesions of the the hippocampal formations protruding in the floor amygdaloid body in animals is associated with mod- of the temporal horns and displayed throughout ifications of emotional behavior. Reviews of the called Kluver-Bucy syndrome, in which the animals complex terminology may be found in Tilney (1939), become placid with no fear or aggression reactions Klingler (1948) and Meyer (1971). The hippocampus with a compulsion to explore objects orally, tactually consists of two cortical lamina each interlocked with or visually, is seen with bilateral amygdalar destruc- the other: Ammon’s horn or the hippocampus prop- tion (Kluver 1952; Kluver and Bucy 1939). Such bilateral lesions in humans cause a decrease in aggressive behavior and a The telencephalon enlarges markedly during devel- marked decrease in emotional excitation but no opment pushing the paleocortex or rhinencephalon signs suggestive of the Kluver-Bucy syndrome (Lilly basally into the mesial temporal lobe. The increase in size of the hippoc- corresponding to a negative mood appear to be un- ampus results in a bulging into the ventricle with a related to the memory loss, which is related to the vascular supply being derived from the hippocampal hippocampus. This sulcus originates from the medial wall of involved in the emotional modifications observed in the ventricle and runs in parallel with the choroidal schizophrenic patients based on the connections fissure. The medial aspect dopaminergic system, which innervates the frontal of the hemisphere shows a longitudinal groove, the cortex and the ventral striatum, is postulated to be hippocampal fissure, oriented parallel to the choroi- the neurochemical feature of this disease. The choroidal and hippocampal fissures the amygdala may be emphasized here, considering arch from the region of the interventricular foramen its reciprocal connections with the dopaminergic to the tip of the inferior horn. The hippocampal arch neurons of the midbrain which give rise to the me- does not show similar development. With a forward growth of the temporal lobes, the ranging cortico-amygdalo-tegmental and hypotha- inferior portion develops and differentiates into the lamic pathways. The lips of the hippocampal fissure give rise E The Hippocampal Formation to the dentate gyrus and the parahippocampal gy- rus. The superior portion of the parahippocampal As far as we know, the first description of the hippoc- gyrus, adjacent to the hippocampal fissure, is the ampus was given by Arantius (1587) and J. A Monotremes; B intermediate stage; C hedgehog and bat; D small precommissural remnant of hippocampus; E rodents; F primates. These include the work of brain invaginates into the ventricles forming the Gastaut and Lammers (1961), Crosby et al. This invagination has two edges: one Blackstaad and Flood (1963), Brodal (1969, 1981), free, called the tela choroidea connecting the choroid Warwick and Williams (1973, 1989), Isaacson and plexus with the original matrix, and one fixed, at- Pribram (1975) and Carpenter (1976, 1996), to which tached to the ventricular surface of the thalamus, the reader should refer. The tenia choroidea is The hippocampal formation may be subdivided the tuft lifted into the ventricular cavity at the basis morphologically into a precommissural, a supra- of the choroid plexus. The The development of the temporal horn pushes the retrocommissural portion represents the hippocam- choroid plexus posteriorly. With this rotation the pal formation, the other parts being vestigial ana- choroid plexus position is reversed, becoming locat- tomical structures.

Type 1 diabetes mellitus skin care brand crossword 1mg decadron amex, controlled on current insulin regimen frequency skin care jogja generic decadron 8 mg mastercard, but states that he used to have difficulty urinating until 3 acne under armpit cheap decadron online visa. What are the patient’s known cardiovascular risk factors, and what is the patient’s Framingham risk score? Describe how you would explain to a patient how to use a digital home blood pressure monitor such as the one shown in Optimal Plan Fig. The risk of hemorrhagic stroke may be increased by the use of aspirin therapy in patients with uncontrolled hypertension. Based on your recommendations, provide appropriate education report of the Joint National Committee on Prevention, Detection, to this patient. Review the American Heart Association Scientific Statement on High Blood Pressure Research and the Councils on Clinical Cardiology the treatment of hypertension in the prevention of and manage- and Epidemiology and Prevention. Management of high blood cotherapeutic regimen for this patient if he had a history of each pressure in African Americans: Consensus Statement of the Hyperten- of the following co-morbidities or characteristics: sion in African Americans Working Group of the International Society • Severe-persistent asthma on Hypertension in Blacks. Besides, I an angiotensin-converting enzyme inhibitor, ramipril, on cardiovascu- think I feel better without the medicines. Effects of medications, his response was “I haven’t been feeling well lately and ramipril on cardiovascular and microvascular outcomes in people with figured maybe my blood pressure was high. Effects of intensive died in his 70’s of a second heart attack; mother died a few years later blood-pressure lowering and low-dose aspirin in patients with hyper- tension: principal results of the Hypertension Optimal Treatment from a stroke. Denies palpitations and chest pain, but states that he did almost • Describe how a pharmacist can educate a patient about hyper- pass out while trimming trees a couple of weeks ago. What signs and symptoms are present that may be related to the Cool to touch, good turgor severity of this patient’s hypertension? As a community pharmacist presented with this patient and Abd his blood pressure, what is your most immediate course of action? What feasible pharmacotherapeutic alternatives are available Genit/Rect for the treatment of this patient’s acute hypertension? Santos resume his atenolol and segment changes, although there does appear to be some T-wave amlodipine as prescribed or would you recommend alternative flattening in the anterior leads. If you would recom- í Assessment mend alternative drug therapy, which drug(s) would you recommend and why? I have been feeling run down, and I haven’t been able to get up the stairs to my bedroom because I get Hypertension is largely an asymptomatic disease. The diagnosis and management of hypertensive progressively worsening dyspnea on exertion over the last 5 days. Reports having headaches recently, but nothing that he would • Develop a pharmacotherapeutic plan for treatment of heart consider unusual or out of the ordinary. Complains of recent abdominal bloat- • Outline a monitoring plan for heart failure that includes both ing and of being awakened the past four evenings to relieve his clinical and laboratory parameters. He reports some weakness in his right lower extremity but • Initiate, titrate, and monitor β-adrenergic blocker therapy in states that it is unchanged from his most recent stroke. There are fine crackles in both lung fields posteriorly noted two-thirds of the way up the lung fields. Note the presence of severe left ventricular dilation and increased left atrial dimension in end diastole (B) that appear to be unchanged from the photographs of end systole (A). The ventricular septum appears to be in nearly the identical position in both films, thus representing akinesia.