Edward S Kraus, M.D.
- Professor of Medicine
https://www.hopkinsmedicine.org/profiles/results/directory/profile/0000620/edward-kraus
Reactions occur 5 to 20 days after transfusion and are due to antibodies undetectable at the time of compatibility testing blood pressure medication lisinopril order 40 mg lasix with amex. More than 30 percent of antibodies disappear with time arrhythmia what to do lasix 100mg online, but recipients can mount anamnestic responses to further stimulation by transfusion pulse pressure variation ppt cheap lasix 40mg without prescription. Delayed hemolytic transfusion reactions may cause severe anemia blood pressure checker purchase lasix 100mg on line, painful events, and even death. Acquiring and maintaining adequate records of previous transfusions and complications arising from them. Screening for newly acquired antibodies 1 to 2 months after each transfusion to detect transient antibodies that cause a subsequent delayed reaction. This may be accomplished by: Typing the patient before transfusion (if this has not already been done) for Rh and Kell blood group antigens to avoid transfusion of cells with these antigens (particularly E, C, and Kell) if the patient lacks them. Although transfusion may be necessary in some patients, an alternative course may be to avoid transfusion and to administer corticosteroids, large doses of erythropoietin, and possibly intravenous immune globulin. Such antibodies may cause febrile reactions that can be prevented by the removal of leukocytes by filtration or washing. These antibodies, and those for serum proteins, can cause allergic reactions that can be prevented by prophylaxis with an antihistamine (Benadryl), leukodepletion, or removal of plasma. Patients alloimmunized to one red cell antigen are more likely to become alloimmunized to others. Transfusions should be given only for clearcut indications, and care should be taken in the selection of units of blood. Patients should be counseled to advise any new physician of their history of alloimmunization and to carry a card or identification bracelet that lists their red blood cell phenotype and any identified antibodies. Patients who have received multiple transfusions should be monitored serially for hepatitis C and other infections (15,16). Parvovirus occurs in 1 in every 40,000 units, and is associated with acute anemic events and multiple sickle cell complications. Repeatedly transfused hemoglobinopathy patients are particularly vulnerable to Yersinia entercolitica and bacteremia from poor skin cleansing before phlebotomy. All patients who develop fever after transfusion need to be assessed immediately for potential bacterial infection. Autoimmune anemia occurs because the recipient produces antibodies against self-antigens, which may persist up to 2 to 3 months before disappearing. In contrast to thalassemia patients, most patients are iron overloaded because of intermittent transfusions throughout their lives. Therefore, a comprehensive program to monitor and treat iron overload is necessary. Measurement of serial serum ferritins may help but can be unreliable because ferritin is an acute phase reactant and values are altered by liver disease, inflammation, and vitamin C stores. Liver biopsy is the most accurate test for iron overload and can be performed safely by an experienced physician. The sample should be of adequate size and sent to a reference lab familiar with liver iron quantitation. Some programs recommend liver biopsies at the start of chelation and every 2 years thereafter. The best indication to begin chelation therapy is a rise in liver iron stores to 7 mg/g dry weight. Alternatively, cumulative transfusions of 120 cc of pure red cells per kilogram of body weight can be used (5). Serum ferritin levels above 1,000 ng/mL in the steady state are helpful, but the risk of under- and overtreatment occurs. All iron-overloaded patients should be followed at comprehensive sickle cell centers that can monitor organ toxicity and provide ongoing education and support. Exchange transfusions and chelation therapy are the only two accepted methods to manage transfusion-related iron overload. Phlebotomy will remove iron in abnormal red cells, which are replaced by normal red cells. Supplementation with vitamin C, 100 to 200 mg per day, may help to increase excretion, especially in those who are vitamin C deficient.
Thus arteria lienalis buy discount lasix 40 mg online, by selective control of the physical parameters of a drug blood pressure medication names starting with a cheap 40mg lasix amex, biologic response may be optimized heart attack song lasix 100 mg generic. Stability the chemical and physical stability of a drug substance alone blood pressure psi buy discount lasix 40 mg on line, and when combined with formulation components, is critical to preparing a successful pharmaceutical product. For a given drug, one type of crystal structure may provide greater stability than other structures and may therefore be preferred. For drugs susceptible to oxidative decomposition, the addition of antioxidant stabilizing agents to the formulation may be required to protect the potency. For drugs destroyed by hydrolysis, protection against moisture in formulation, processing, and packaging may be required to prevent decomposition. They all must be prepared in indistinguishable dosage forms (look alike, taste alike, and so on) and packaged with coded labels to reduce possible bias when blinded studies are called for in the clinical protocol. At the conclusion of the clinical study, the codes for the products administered are broken and the clinical results statistically evaluated. Some studies are open label, in which case, all parties may know what products are administered. Some pharmaceutical companies have special units for the preparation, analytical control, coding, packaging, labeling, shipping, and record maintenance of clinical supplies. Other companies integrate this activity within their existing drug product development and production operations. Still other companies employ contract firms specializing in this field to prepare and manage their clinical trial materials program. In all clinical study programs, the package label of the investigational drug must bear the statement "Caution: new drug-limited by federal [or United States] law to investigational use. Blister packaging is commonly used in clinical studies, with immediate labels containing the clinical study or protocol number, patient identification number, sponsor number, directions for use, code number to distinguish between investigational drug, placebo, and/or comparator product, and other relevant information. Records of the disposition of the drug must be maintained by patient number, dates, and quantities administered. When an investigation is terminated, suspended, discontinued, or complete, all unused clinical supplies must be returned to the sponsor and an accounting made of used and unused products. This is to protect the rights and safety of the subjects and to ensure that the investigational plan is sound and is designed to achieve the stated objectives. The sponsor may be an individual (a sponsorinvestigator), a pharmaceutical company, governmental agency, academic institution, or some other private or public organization. The sponsor may actually conduct the study or employ, designate, or contract other qualified persons to do so. Nowadays, many contract research organizations conduct all or designated portions of clinical studies or clinical drug trials for others through contractual arrangements. This may involve changes of dosing levels, testing procedures, the addition of new investigators, additional sites for the study, and so on. For many years, women and the elderly were included only rarely in clinical drug investigations. Women of childbearing age were excluded from early drug tests out of fear that the subject would become pregnant during the investigation with possible harm to the fetus. Pregnancy is a concern in drug investigations because drugs are readily transported from the maternal to the fetal circulation (39). Because of undeveloped drug detoxication and excretion mechanisms in the fetus, concentrations of drugs may actually reach a higher level in the fetus than in the maternal circulation, with toxic levels resulting. There are other instances in which drug studies or drug use during pregnancy is justified, for example, agents intended to prevent Rh immunization and hemolytic disease of the newborn (41). Furthermore, the elderly have a greater incidence of chronic illness and multiple disease states than younger adults, and as a result, take multiple medications daily, increasing the potential for drugdrug interactions. It is well known that there are interethnic variations both in disease incidence and in biologic response to some medications, and these factors must be considered in the clinical evaluation of drug substances (42). These criteria may relate to age, sex (as qualified earlier), smoking, health status. Each subject in a clinical investigation must participate willingly and with full knowledge of the benefits and risks associated with the investigation. These elements of informed consent, and additional protections that apply to prisoners in clinical investigations, must be in conformance with the Code of Federal Regulations (44). Individuals who agree to be subjects in an investigation indicate their consent by signing the form or document containing this information.
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Chemotherapy should be initiated within 12 weeks of surgical removal of the primary tumor arrhythmia flowchart buy lasix 100 mg line. Dose intensity is defined as the amount of drug administered per unit of time and is typically reported in milligrams per square meter of body surface area per week (mg/m2/ week) blood pressure 9040 purchase 40mg lasix with visa. Increasing dose blood pressure medication kinds purchase lasix 100mg without a prescription, decreasing time between doses hypertension and headaches buy lasix 100 mg otc, or both can increase dose intensity. Dose density is one way of achieving dose intensity, but not by increasing the amount of drug given, as occurs with dose escalation, but instead by decreasing the time between treatment cycles. But increasing doses beyond those contained in standard treatment regimens does not appear to be beneficial and may be harmful. Using a 2 Ч 2 factorial design, investigators randomized node-positive breast cancer patients after surgery to compare sequential versus concurrent chemotherapy, and standard dose versus dose density. Patients in the concurrent every 2-week group (group 4) had significantly more regimen-related toxicity, including a very high rate of red blood cell transfusions for anemia (13% of cycles). Many studies with anthracyclines (without taxanes) appear to indicate no benefit from a dose-dense approach to drug administration. However, data with the taxanes, especially paclitaxel, appear to support a dose-dense (not intense) approach, with weekly therapy producing optimal outcomes. A direct comparison between taxane dosing intervals was evaluated in the North American Breast Cancer Intergroup Trial E1199 which randomized patients in a 2 Ч 2 factorial design to receive doxorubicin and cyclophosphamide for four cycles every 3 weeks followed by either weekly or 3-weekly paclitaxel or docetaxel. Although other trials have attempted to investigate dose-dense regimens, they also have other variables that were altered that could potentially impact the outcomes. Consequently, they do not directly address the question and their results may be influenced by factors other than dose density. A detailed discussion of these nuances is beyond the scope of this chapter and the reader is referred to excellent references on this topic for further information. Thorough discussion regarding the risks and benefits each individual patient may face is imperative given the uncertainty surrounding these regimens. A major focus of clinical investigations in the past was the use of high-dose chemotherapy regimens as adjuvant therapy. Because bone marrow suppression is the dose-limiting toxicity for most chemotherapeutic agents, high-dose chemotherapy regimens followed by colony-stimulating factors or reinfusion of autologous hematopoietic stem cells were developed. Several cooperative groups have conducted trials of high-dose chemotherapy with stem cell support versus conventional adjuvant therapy. Based on the available evidence, this approach to therapy is currently not recommended outside the context of a clinical trial. The short-term toxic effects of chemotherapy used in the adjuvant setting are generally well tolerated. Although a number of investigators have demonstrated a reduction in quality-of-life, most patients are able to maintain a reasonable level of function and emotional and social well-being during treatment. Increased attention to the impact of symptoms on quality-of-life may account for some of this improvement. In addition, more effective antiemetics have become available to assist in managing chemotherapyinduced nausea and vomiting, and colony-stimulating factors are often helpful in preventing febrile neutropenia, particularly in elderly patients or patients receiving dose-dense chemotherapy regimens. Despite the use of newer antiemetics for prevention of nausea and vomiting, many women still have difficulty with this side effect and delayed nausea and vomiting remains problematic in some patients. The use of growth factors to support some adjuvant chemotherapy regimens may be required. Many other side effects are common with the chemotherapy regimens employed for treatment of early stage breast cancer and patients should be appropriately counseled regarding the likelihood of alopecia, weight gain, and fatigue. Patients who are menstruating will often experience a cessation of menses that may not return; cessation of menses may be accompanied by signs and symptoms of menopause. Deep vein thrombosis has been reported in women receiving combination chemotherapy regimens. Cardiomyopathy induced by doxorubicin occurs in less than 1% of women whose total dose of doxorubicin is less than 320 mg/ m2. It should be noted that epirubicin in the adjuvant setting is usually given at a dose of 100 to 120 mg/m2. Taxanes are often associated with hypersensitivity reactions, peripheral neuropathy and/or myalgias and arthralgias for several days following the infusion. In addition, it is currently not possible to accurately predict who will attain this survival benefit. Studies have reported that most breast cancer patients would accept severe toxicity from treatment to achieve as little as a 1% to 5% improvement in survival.
If a suspension remains unaltered by autoclaving blood pressure facts buy lasix 100mg fast delivery, this method is generally employed to sterilize the final product hypertension portal buy cheap lasix 100mg. Because parenteral emulsions blood pressure screening purchase lasix 100mg line, which are dispersions or suspensions of a liquid throughout another liquid heart attack vital signs cheap 40 mg lasix visa, are generally destroyed by autoclaving, an alternative method of sterilization must be employed for this type of injectable. Some injections are packaged as dry solids rather than in conjunction with a solvent or vehicle because the therapeutic agent is unstable in the presence of the liquid component. These dry powders are packaged in the final container to be reconstituted, generally to a solution or less frequently a suspension. The method of sterilization of the powder may be dry heat or another appropriate method. These are examples of sterile drugs prepared and packaged without pharmaceutical additives such as buffers, preservatives, stabilizers, and tonicity agents: Ampicillin sodium Ceftizoxime sodium Ceftazidime sodium Cefuroxime sodium Kanamycin sulfate Nafcillin sodium Penicillin G benzathine Streptomycin sulfate Tobramycin sulfate Antibiotics are prepared industrially in large fermentation tanks. Sterile drugs formulated with pharmaceutical additives and intended to be reconstituted prior to injection include the following: Cyclophosphamide Dactinomycin Erythromycin lactobionate Hydrocortisone sodium succinate Mitomycin Nafcillin sodium Penicillin G potassium Vinblastine sulfate Sometimes a liquid is packaged along with the dry powder for use at the time of reconstitution. The bottom compartment can be filled either with a liquid that is frozen and dried to make a lyophilized product or with a powder. The diluent in the top contains a preservative and sometimes one or more active ingredients. To use the vial, the dust cover is removed; pressure is applied with the thumb to the top plunger, which dislodges the center seal; and the vial is shaken well. The top of the plunger is then swabbed with a disinfectant; the syringe needle inserted through the target circle on the plunger; and the contents of the vial withdrawn into the syringe. The Mix-O-Vial offers stability of the product until it is activated, convenience, fast operation, and safety as regards the right drug with the proper diluent in the correct proportions. More frequently, the solvent or vehicle is not provided, but the label generally lists suitable solvents. Sodium chloride injection and sterile water for injection are perhaps most frequently employed to reconstitute dry-packaged injections. To facilitate dissolution, the dry powder is prevented from caking upon standing by the appropriate means, including lyophilization. Powders so treated form a honeycomb lattice structure that is rapidly penetrated by the liquid, and solution is rapid because of the large surface area of powder exposed. Pfizer manufactures the Mix-O-Vial, which incorporates the cover as part of the plunger. Once mixed, the small circle of plastic that covers the injection site is removed. With this system, antibiotics and other drugs do not have to be mixed until just prior to administration. The vials containing the medication and the piggybacks (50 to 250 mL of dextrose 5% in water injection, 0. This simple process is performed by external manipulation of the container, preserving the closed, sterile system. Vantage system can be used within 30 days of removal of the diluent container from the outer wrapping. This system is an integrated drug transfer mechanism with a protective shield surrounding the attached transfer needle. Reconstitution and transfer of the drug into an infusion bag are accomplished safely, quickly, and with few materials. The needle is inserted into the port of the infusion bag and the transfer set is pushed down toward the vial until it clicks. Then the minibag is squeezed and released to transfer the drug back into the infusion bag. Reconstituted cefazolin is stable for 48 hours at room temperature and for 10 days when refrigerated (5°C or 41°F). If the container is made of glass, it must be clear and colorless or light amber to permit inspection of its contents. Injections are placed either in single-dose containers or in multiple-dose containers. By definition: Single-dose container: A hermetic container holding a quantity of sterile drug intended for parenteral administration as a single dose; when opened, it cannot be resealed with assurance that sterility has been maintained. Multiple-dose container: A hermetic container that permits withdrawal of successive portions of the contents without changing the strength, quality, or purity of the remaining portion.
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