Mark Corson

By L. Kadok. Bob Jones University. 2018.

Universal Free E-Book Store Chapter 15 Personalized Management of Pulmonary Disorders Introduction There are a large number of pulmonary disorders some of which present challenges in management purchase 6 mg exelon free shipping. There is still limited information on pharmacogenomics and pharmacogenetics of pulmonary therapeutics buy exelon 3 mg mastercard. Personalized approaches to some pulmonary diseases will be described briefly as examples in this chapter generic exelon 1.5 mg on line. Role of Genetic Ancestory in Lung Function A study shows that incorporating measures of individual genetic ancestry into nor- mative equations of lung function in persons who identify themselves as African Americans may provide more accurate predictions than formulas based on self- reported ancestry alone (Kumar et al. The same argument may apply to other ancestrally defined groups; further studies in this area are necessary. Further studies are also needed to determine whether estimates informed by genetic ancestry are associated with health outcomes. The authors noted that environmental factors such as premature birth, prenatal nutrition, and socioeconomic status may also play an important role in the association between lung function and ancestry. It remains to be seen whether differences associated with race or ethnic group in the response to medications that control asthma are more tightly associated with estimates of ances- try. Although measures of individual genetic ancestry may foster the development of personalized medicine, large clinical trials and cohort studies that include assess- ments of genetic ancestry are needed to determine whether measures of ancestry are more useful clinically than a reliance on self-identified race. Biomarkers of pulmonary disorders with exception of lung cancer are listed in Table 15. It is there- fore of interest to identify biomarkers that are associated with impaired lung func- tion. This indicates that combination of two biomarkers yielded more information than assessing them one by one when analyzing the association between systemic inflammation and lung function. Biomarkers of Oxidative Stress in Lung Diseases Oxidative stress is the hallmark of various chronic inflammatory lung diseases. Traditionally, the measurement of these biomarkers has involved inva- sive procedures to procure the samples or to examine the affected compartments, to the patient’s discomfort. Oxidative stress biomarkers also have been measured for various antioxidants in disease prognosis. Despite its prevalence, there are many challenges to proper diagnosis and management of pneumonia. There is no accurate and timely gold standard to differentiate bacterial from viral disease, and there are limitations in precise risk stratification of patients to ensure appropriate site-of-care decisions. In addition, lower levels of the coagulation marker protein C were independently associated with an increased risk of death. These associations exist despite consistent use of lung protective ventilation and persist even when control- ling for clinical factors that also impact upon outcomes. It might help prevent further tissue damage by improving oxy- gen and nutrient delivery to the tissues, while helping to decrease the amount of toxic oxygen species. Personalized Therapy of Asthma Asthma affects 5–7 % of the population of North America and may affect more than 150 million persons worldwide. It is a chronic inflammatory dis- ease but there is no clear definition of the disease and no single symptom, physical finding or laboratory test is diagnostic of this condition. The disease is manifested as variable airflow obstruction and recurrent bouts of respiratory symptoms. Little is known about the mechanisms that determine asthma development and severity and why some individuals have mild symptoms and require medication only when symptomatic whereas others have continuous symptoms despite high doses of several medica- tions (refractory asthma). Asthma is often triggered by an allergic response and the environmental factors play an important role in manifestations of the disease. Although there is a significant hereditary component, genetic studies have been dif- ficult to perform and results have been difficult to interpret. Only a few therapeutic agents based on novel mechanisms of action have been developed over the past two decades. Asthma is a complex disease with marked heterogeneity in the clinical course and in the response to treatment. Despite treatment with inhaled glucocorti- coids, many patients continue to have uncontrolled asthma that requires more intensive therapy. Approximately one in three patients with asthma who use inhaled glucocorticoids may not benefit from this therapy. Biomarkers and some of the other methods for guiding therapy of asthma are described here. Biomarkers of Asthma Although the aim of management of patients with asthma is to control their symp- toms and prevent exacerbations and morbidity of the disease, optimal management may require assessment and monitoring of biomarkers, i. Universal Free E-Book Store 516 15 Personalized Management of Pulmonary Disorders Biomarker for Rhinovirus-Induced Asthma Exacerbation Clinical observations suggest that rhinovirus infection induces a specific inflamma- tory response in predisposed individuals that results in worsened asthmatic symp- toms and increased airway inflammation. Biomarkers for Predicting Response to Corticosteroid Therapy International guidelines on the management of asthma support the early introduction of corticosteroids to control symptoms and to improve lung function by reducing airway inflammation. However, not all individuals respond to corticosteroids to the same extent and it would be a desirable to be able to predict the response to cortico- steroid treatment. Several biomarkers have been assessed following treatment with corticosteroids including measures of lung function, peripheral blood and sputum indices of inflammation, exhaled gases and breath condensates. Of these, sputum eosinophilia has been demonstrated to be the best predictor of a short-term response to corticoste- roids. More importantly, directing treatment at normalizing the sputum eosinophil count can substantially reduce severe exacerbations. The widespread utilization of sputum induction is hampered because the procedure is relatively labor intensive. The challenge now is to either simplify the measurement of a sputum eosinophilia or to identify another inflammatory marker with a similar efficacy as the sputum eosino- phil count in predicting both the short- and long-term responses to corticosteroids. Cytokines as Biomarkers of Asthma Severity Severe asthma is characterized by elevated levels of proinflammatory cytokines and neutrophilic inflammation in the airways. Blood cytokines, biomarkers of systemic inflammation, may be a feature of increased inflammation in severe asthma.

Other order 6mg exelon otc, less potent stimuli of vasopressin release include pregnancy discount exelon 6mg fast delivery, nausea buy cheap exelon 4.5mg online, pain, stress, and hypoglycemia. This hormone acts on the principal cell in the distal convoluted tubule of the kidney to cause resorption of water. This occurs through nuclear mecha- nisms encoded by the aquaporin-2 gene that cause water channels to be inserted into the luminal membrane. The net effect is to cause the passive resorption of water along the os- motic gradient in the distal convoluted tubule. Activation of β2-adrenergic receptors in- duces cellular uptake of potassium and promotes insulin secretion by pancreatic islet β cells. Severe hy- pokalemia leads to progressive weakness, hypoventilation and eventually complete paral- ysis. The electrocardiogram findings are common but do not correlate with the degree of hypokalemia in the serum. The quantity of water required to correct a free water deficit in hypernatremic patients can be estimated from the following equation: Water deficit = [(plasma Na – 140)/140] × total body water Total body water is approximately 50% of lean body mass in men and 40% of lean body mass in women. In calculating the rate of water replacement, ongoing losses should be + accounted for and plasma Na should be lowered by no more than 0. More rapid administration of water and normalization of serum so- dium concentration may result in a rapid influx of water into cells that have already un- dergone osmotic normalization. The main differential diagnosis is acute glomerulonephritis, but if an individual is on a culprit drug, the drug should be discontinued as an initial step. Discontinuation of the drug usually leads to complete re- versal of the renal injury, although in severe cases, prednisone may be used to improve re- covery. The clinical picture does not suggest relapse of endocarditis, worsening valvular dysfunction, or new infectious process such as a infection of the central venous catheter. Antistreptol- ysin O titers are elevated in cases of poststreptococcal glomerulonephritis due to group A streptococcus, but would not be elevated in S. The risk factors for developing hypotension during hemodialysis include ex- cessive ultrafiltration, reduced intravascular volume before dialysis, impaired autonomic responses, osmolar shifts, food intake before dialysis, impaired cardiac function, and use of antihypertensive agents. The hypotension is usually managed with fluid administration and by decreasing the ultrafiltration rate. Anaphylactoid reac- tions to the dialyzer once were common but are also decreasing in frequency with the use of newer-generation dialysis membranes. Fever is not a usual complication of hemodialysis but suggests the presence of an infection of the dialysis access site. Symptoms of hypercalcemia depend on the severity and time course of its development. Patients may progress to complain of vague neuropsychi- atric symptoms including trouble concentrating, personality changes, and depression. Severe hypercalcemia, particularly if it develops acutely, may result in lethargy, stupor, or coma. Only after volume has been restored should loop diuretics be used to decrease se- rum calcium. Zoledronic acid is indicated if there is increased calcium mobilization from bone, as in malignancy or severe hyperparathyroidism. Intravenous phosphate is not indi- cated as it chelates calcium and may deposit in tissue and cause extensive organ damage if the calcium-phosphate product is >65. The mechanism of the hypercalcemia of sarcoidosis is related to excess vitamin D, therefore calcitriol would be contraindicated. Thiazide diuretics, calcium channel blockers, or centrally acting alphablockers are better choices for an antihypertensive agent in a pa- tient with bilateral renal artery stenosis. Factors such as infection, drugs, position, and exercise impact solute and water clearance. In the developed world, hemodialysis is often the preferred method for renal replacement for pa- tients. However, in poorer countries where access to hemodialysis centers is limited, peri- toneal dialysis is used more commonly. Residual renal function alters the dose of dialysis but does not impact the mode of dialysis. Moreover, patients with no residual renal func- tion who receive peritoneal dialysis are at higher risk of uremia than patients on hemodial- ysis. High-transporters through the peritoneum require more frequent doses of peritoneal dialysis, potentially negating the benefit of this modality. Patients with prior abdominal surgeries often have difficulty with peritoneal dialysis catheter placement and dialysate delivery. The calculated urine anion gap (Na + K – Cl ) is +3; thus, the acidosis is un- likely to be due to gastrointestinal bicarbonate loss. This condition may be associated with calcium phosphate stones and nephrocalcinosis. The history and labora- tory features are also consistent with this lesion: some associated hypertension, diminution in creatinine clearance, and a relatively inactive urine sediment. The “nephropathy of obesity” may be associated with this lesion secondary to hyperfiltration; this condition may be more likely to occur in obese patients with hypoxemia, obstructive sleep apnea, and right-sided heart failure. Hypertensive nephrosclerosis exhibits more prominent vascular changes and patchy, ischemic, totally sclerosed glomeruli. In addition, nephrosclerosis seldom is associated with nephrotic-range proteinuria. Minimal-change disease usually is associated with sympto- matic edema and normal-appearing glomeruli as demonstrated on light microscopy. This pa- tient’s presentation is consistent with that of membranous nephropathy, but the biopsy is not.

A 45-year-old man with a 60-pack/year (A) Dopamine history of smoking presents to his primary (B) Phentolamine care provider with loss of appetite purchase exelon 4.5 mg with visa, nausea purchase exelon 4.5mg, (C) Pancuronium vomiting purchase 4.5 mg exelon otc, and muscle weakness. Laboratory ble for both asthma and angina now has a kid- results reveal low levels of sodium, which in this ney stone stuck in his right ureter. Which 326 Pharmacology medication might be helpful for this patient’s (C) Chlordiazepoxide symptoms? A 57-year-old man with a strong family (E) Allopurinol history of Parkinson disease sees a neurologist for an evaluation. Which of the following is a common adverse neurologist notes a slight pill-rolling tremor effect of quinidine? He begins treat- (A) Cinchonism ment with levodopa, along with the addition of (B) Lupuslike syndrome carbidopa. What is the mechanism of action of b-block- (C) Inhibits catechol-O-methyltransferase ers in heart disease? The patient in the previous question returns to see his neurologist 3 years later. Which of the following would be useful in the patient’s symptoms have progressed, and the management of arrhythmia due to Wolf- he now has marked bradykinesia and a pro- Parkinson-White syndrome? Which of the following would be a good (A) Memantine option to help a patient fall asleep with minimal (B) Donepezil ‘‘hangover’’? Risperidone works primarily through inhi- psychiatrist with expertise in addiction medi- bition of receptors for cine. He explains that he has recently received (A) Dopamine his third drunk driving citation and fears losing (B) Serotonin his license to practice unless he stops drinking (C) Histamine altogether. He tells the physician that he doesn’t (E) Norepinephrine have time to attend Alcoholics Anonymous and ‘‘wants a pill. A 7-year-old boy is brought to the neurolo- is something that might work if the patient is gist by his mother. What agent is the physician teacher says there are times in class when he considering? Which of the following can be used to treat (C) Thrombocytopenia a 22-year-old with a recent diagnosis of (D) Aplastic anemia schizophrenia? Which of the following agents is approved (C) Dantrolene for treatment of diabetic neuropathy? A 5-year-old boy is brought to the emer- (C) Agranulocytosis gency room by his parents after they found (D) Photosensitivity him with an empty bottle of aspirin. While the emergent treatment that may cause hemorrhagic cystitis and is started, a sample is drawn for an arterial cardiomyopathy? What pattern is most (A) Azathioprine likely to be indicated by the arterial blood gas (B) Cyclosporine values? Which of the following is an antidote for agent that has been shown to help patients with iron overdose? Which of the following is true regarding provide the best relief from episodic attacks of infliximab? A 56-year-old woman with severe rheuma- toid arthritis returns to see her rheumatologist. Which of the following is useful in an acute She had been referred to a gastroenterologist, gout attack? At this point, what would be reasona- (E) Celecoxib ble for the rheumatologist to prescribe? He is G1–S transition referred to a gastroenterologist, who performs (E) It inhibits proliferation of promyelocytes esophogastroduodenoscopy with biopsy that Comprehensive Examination 329 demonstrates ulcers with the presence of 51. Use of which of the follow- and she still complains of bloody diarrhea, ing regimens would provide the most effective fever, and weight loss. The gastroen- and omeprazole terologist could consider using which of the fol- (B) Pepto Bismol, metronidazole, tetracycline, lowing agents? An 83-year-old man with multiple medical of theophylline include problems develops worsening constipation dur- (A) Seizures ing his hospitalization for lower extremity cellu- (B) Arrhythmias litis. Which of the following is an appropri- (D) Nausea and vomiting ate choice and why? A 62-year-old male alcoholic being treated (B) An osmotic agent, such as senna, which is for non-insulin-dependent diabetes mellitus administered rectally comes to the emergency department with a (C) A stool softener such as lactulose adminis- 1-hour history of nausea, vomiting, headache, tered rectally hypotension, and profuse sweating. What is the (D) A stool softener such as methylcellulose most likely causative agent? A 35-year-old intravenous drug abuser in a methadone maintenance program is admitted 54. An 81-year-old man with a history of to the hospital for a work-up of suspected pul- coronary artery disease and a recent diagnosis monary tuberculosis. While in the hospital, he of hypothyroidism presents to the emergency complains of diarrhea and cramping. After stool department with an acute myocardial studies return with a negative result, you decide infarction. Which of the following would be an appro- acute exacerbation of lupus erythematosus priate treatment to begin in a patient with complains of pain on eating. It is likely that the acquisition of antibiotic he smells like alcohol and he is flush, warm, resistance in gram-negative bacilli such as and uncomfortable. A 30-year-old patient is undergoing chemo- therapy for Hodgkin disease and develops a 61. Which of the following can occur in an adult fever, prompting an admission by his oncolo- patient treated with chloramphenicol?