Prazosin

Robert T. Eberhardt, MD

• Department of Medicine
• Section of Cardiovascular Medicine
• Vascular Medicine Program
• Boston University School of Medicine
• Boston, MA

Interference with the metabolism of drugs such as theophylline and carbamazepine has been reported for clarithromycin (see ure 32 cholesterol lowering foods nuts prazosin 5 mg line. Clarithromycin is oxidized to the 14hydroxy derivative cholesterol levels natural remedies generic 5 mg prazosin amex, which retains antibiotic activity cholesterol lowering foods in sri lanka purchase prazosin with amex. Excretion: Erythromycin and azithromycin are primarily concentrated and excreted in an active form in the bile (see ure 32 cholesterol medication fibrates purchase prazosin 5mg amex. In contrast, clarithromycin and its metabolites are eliminated by the kidney as well as the liver, and it is recommended that the dosage of this drug be adjusted in patients with compromised renal function. Epigastric distress: this side effect is common and can lead to poor patient compliance for erythromycin. Clarithromycin and azithromycin seem to be better tolerated by the patient, but gastrointestinal problems are their most common side effects ure 32. Cholestatic jaundice: this side effect occurs especially with the estolate form of erythromycin, presumably as the result of a hypersensitivity reaction to the estolate form (the lauryl salt of the propionyl ester of erythromycin). Ototoxicity: Transient deafness has been associated with erythromycin, especially at high dosages. Similarly, patients who are renally compromised should be given telithromycin with caution. Interactions: Erythromycin, telithromycin, and clarithromycin inhibit the hepatic metabolism of a number of drugs, which can lead to toxic accumulations of these compounds ure 32. In this case, the antibiotic eliminates a species of intestinal flora that ordinarily inactivates digoxin, thus leading to greater reabsorption of the drug from the enterohepatic circulation. However, because of its toxicity, its use is restricted to lifethreatening infections for which no alternatives exist. Mechanism of action the drug binds to the bacterial 50S ribosomal subunit and inhibits protein synthesis at the peptidyl transferase reaction ure 32. Because of the similarity of mammalian mitochondrial ribosomes to those of bacteria, protein synthesis in these organelles may be inhibited at high circulating chloramphenicol levels, producing bone marrow toxicity. Antim icrobial spectrum Chloramphenicol, a broadspectrum antibiotic, is active not only against bacteria but also against other microorganisms, such as rickettsiae. The drug is either bactericidal or (more commonly) bacteriostatic, depending on the organism. Resistance Resistance is conferred by the presence of an R factor that codes for an acetyl coenzyme A transferase. Another mechanism for resistance is associated with an inability of the antibiotic to penetrate the organism. Pharm acokinetics Chloramphenicol may be administered either intravenously or orally ure 32. It is completely absorbed via the oral route because of its lipophilic nature, and is widely distributed throughout the body. Excretion of the drug depends on its conversion in the liver to a glucuronide, which is then secreted by the renal tubule. Only about 10 percent of the parent compound is excreted by glomerular filtration. Adverse effects the clinical use of chloramphenicol is limited to lifethreatening infections because of the serious adverse effects associated with its administration. In addition to gastrointestinal upsets, overgrowth of Candida albicans may appear on mucous membranes. Anemias: Hemolytic anemia occurs in patients with low levels of glucose 6phosphate dehydrogenase. Other types of anemia occurring as a side effect of chloramphenicol include reversible anemia, which is apparently doserelated and occurs concomitantly with therapy, and aplastic anemia, which although rare is idiosyncratic and usually fatal. Gray baby syndrome: this adverse effect occurs in neonates if the dosage regimen of chloramphenicol is not properly adjusted. Neonates have a low capacity to glucuronylate the antibiotic, and they have underdeveloped renal function. Therefore, neonates have a decreased ability to excrete the drug, which accumulates to levels that interfere with the function of mitochondrial ribosomes. This leads to poor feeding, depressed breathing, cardiovascular collapse, cyanosis (hence the term a figray babya ), and death. Adults who have received very high doses of the drug can also exhibit this toxicity. Interactions: Chloramphenicol is able to inhibit some of the hepatic mixedfunction oxidases and, thus, blocks the metabolism of such drugs as warfarin, phenytoin, tolbutamide, and chlorpropamide, thereby elevating their concentrations and potentiating their effects ure 32. Clindamycin is employed primarily in the treatment of infections caused by anaerobic bacteria, such as Bacteroides fragilis, which often causes abdominal infections associated with trauma. However, it is also significantly active against nonenterococcal, grampositive cocci. Resistance mechanisms are the same as those for erythromycin, and cross resistance has been described. Adequate levels of clindamycin are not achieved in the brain, even when meninges are inflamed. The drug is excreted into the bile or urine by glomerular filtration, but therapeutically effective levels of the parent drug are not achieved in the urine ure 32. Accumulation has been reported in patients with either severely compromised renal function or hepatic failure. In addition to skin rashes, the most serious adverse effect is potentially fatal pseudomembranous colitis caused by overgrowth of C. Oral administration of either metronidazole or vancomycin is usually effective in controlling this serious problem. Mechanism of action Each component of this combination drug binds to a separate site on the 50S bacterial ribosome, forming a stable ternary complex. In some cases, the enzymatic modification can change the action from bactericidal to bacteriostatic. Antibacterial spectrum the combination drug is active primarily against grampositive cocci, including those resistant to other antibiotics (for example, methicillinresistant staphylococci). Pharm acokinetics Quinupristin/dalfopristin is injected intravenously in a 5 percent dextrose solution (the drug is incompatible with a saline medium). The products are less active than the parent in the case of quinupristin and are equally active in the case of dalfopristin. Most of the parent drugs and metabolites are cleared through the liver and eliminated via the bile into the feces ure 32. Venous irritation: this commonly occurs when quinupristin/dalfopristin is administered through a peripheral rather than a central line. Arthralgia and myalgia: these have been reported when higher levels of the drugs are employed. Hyperbilirubinemia: Total bilirubin is elevated in about 25 percent of patients, resulting from a competition with the antibiotic for excretion. A drug interaction with digoxin appears to occur by the same mechanism as that caused by erythromycin. Mechanism of action the drug inhibits bacterial protein synthesis by inhibiting the formation of the 70S initiation complex. Linezolid binds to a site on the 50S subunit near the interface with the 30S subunit ure 32. Resistance Decreased binding to the target site confers resistance on the organism. Antibacterial spectrum the antibacterial action of linezolid is directed primarily against grampositive organisms, such as staphylococci, streptococci, and enterococci, as well as Corynebacterium species and Listeria monocytogenes ure 32. However, its main clinical use is against the resistant organisms mentioned above. Like other agents that interfere with bacterial protein synthesis, linezolid is bacteriostatic. The drug is widely distributed throughout the body, having a volume of distribution of 40 to 50 liters. Two metabolites that are oxidation products have been identified, one of which has antimicrobial activity. Adverse effects Linezolid is welltolerated, with some reports of gastrointestinal upset, nausea, and diarrhea, as well as headaches and rash. Thrombocytopenia was found to occur in about 2 percent of patients who were on the drug for longer than 2 weeks. Although no reports have appeared that linezolid inhibits monoamine oxidase activity, patients are cautioned not to consume large quantities of tyraminecontaining foods.

Contraindications: Heparin is contraindicated for patients who are hypersensitive to it cholesterol test machine uk purchase prazosin 5 mg mastercard, have bleeding disorders cholesterol medication and orange juice generic 5mg prazosin overnight delivery, are alcoholics cholesterol free foods cheap prazosin 5mg with visa, or are having or have had recent surgery of the brain cholesterol is buy prazosin uk, eye, or spinal cord. One molecule of lepirudin binds to one molecule of thrombin, resulting in blockade of the thrombogenic activity of thrombin. Bleeding is the major adverse effect of treatment with lepirudin, and it can be exacerbated by concomitant thrombolytic therapy, such as treatment with streptokinase or alteplase. Because renal elimination of the complex is slower than that of the free drug, the anticoagulant effect may be increased. Because argatroban is metabolized in the liver, it may be used in patients with renal dysfunction but it should be used cautiously in patients with hepatic impairment. Food and Drug Administration for use in the prophylaxis of deepvein thrombosis that could lead to pulmonary embolism in patients undergoing hip fracture surgery, hip replacement surgery, and knee replacement surgery. It is well absorbed from the subcutaneous route with a predictable pharmacokinetic profile. Fondaparinux is eliminated in urine mainly as unchanged drug with an elimination halflife of 17 to 21 hours. Initially used as a rodenticide, warfarin is now widely employed clinically as an oral anticoagulant. The potential morbidity associated with the use of warfarin makes it important to identify those patients who are truly at risk for thrombosis. The Icarboxyglutamyl residues bind calcium ions, which are essential for interaction between the coagulation factors and platelet membranes. The reduced vitamin K cofactor is converted to vitamin K epoxide during the reaction. The anticoagulant effects of warfarin can be overcome by the administration of vitamin K. However, reversal following administration of vitamin K takes approximately 24 hours (the time necessary for degradation of already synthesized clotting factors). Therapeutic uses: Warfarin is used to prevent the progression or recurrence of acute deepvein thrombosis or pulmonary embolism after initial heparin treatment. It is also used for the prevention of venous thromboembolism during orthopaedic or gynecologic surgery. Prophylactically, it is used in patients with acute myocardial infarction, prosthetic heart valves, or chronic atrial fibrillation. Absorption: Warfarin is rapidly absorbed after oral administration (100% bioavailability with little individual patient variation). Although food may delay absorption, it does not affect the extent of absorption of the drug. Warfarin is 99 percent bound to plasma albumin, which prevents its diffusion into the cerebrospinal fluid, urine, and breast milk. However, drugs that have a greater affinity for the albumin binding site, such as sulfonamides, can displace the anticoagulant and lead to a transient, elevated activity. The mean half life of warfarin is approximately 40 hours, but this value is highly variable among individuals. Prothrombin time, a measure of the extrinsic pathway, may be used to monitor warfarin therapy. Fate: the products of warfarin metabolism, catalyzed by the cytochrome P450 system, are inactive. Bleeding disorders: the principal untoward reaction caused by warfarin treatment is hemorrhage. Therefore, it is important to frequently monitor and adjust the anticoagulant effect. Minor bleeding may be treated by withdrawal of the drug and administration of oral vitamin K1; severe bleeding requires that greater doses of the vitamin be given intravenously. Whole blood, frozen plasma, or plasma concentrates of the blood factors may also be employed to arrest hemorrhaging. Purple toe syndrome, a painful, bluetinged discoloration of the toe caused by cholesterol emboli from plaques, has also been observed with warfarin therapy. Drug interactions: Warfarin has numerous drug interactions that may potentiate or attenuate its anticoagulant effect. Contraindications: Warfarin should never be used during pregnancy, because it is teratogenic and can cause abortion as well as birth defects. Streptokinase, one of the first such agents to be approved, causes a systemic fibrinolytic state that can lead to bleeding problems. Clinical experience has shown nearly equal efficacy between streptokinase and alteplase. Unfortunately, thrombolytic therapy is unsuccessful in about 20 percent of infarcted arteries, and about 15 percent of the arteries that are opened will later close again. In the case of acute myocardial infarction, the thrombolytic drugs are reserved for those instances when angioplasty is not an option or until the patient can be taken to a facility that performs percutaneous coronary interventions. All act either directly or indirectly to convert plasminogen to plasmin, which in turn cleaves fibrin, thus lysing thrombi (see ure 20. Clot dissolution and reperfusion occur with a higher frequency when therapy is initiated early after clot formation, because clots become more resistant to lysis as they age. Unfortunately, increased local thrombi may occur as the clot dissolves, leading to enhanced platelet aggregability and thrombosis. Strategies to prevent this include administration of antiplatelet drugs, such as aspirin, or antithrombotics, such as heparin. Therapeutic uses: Originally used for the treatment of deepvein thrombosis and serious pulmonary embolism, thrombolytic drugs are now being used less frequently for these conditions. However, thrombolytic agents are helpful in restoring catheter and shunt function, by lysing clots causing occlusions. Pharmacokinetics: For myocardial infarction, intracoronary delivery of the drugs is the most reliable in terms of achieving recanalization. However, cardiac catheterization may not be possible in the 2 to 6hour a fitherapeutic window, a beyond which significant myocardial salvage becomes less likely. Thus, thrombolytic agents are usually administered intravenously, because this route is rapid, is inexpensive, and does not have the risks of catheterization. Adverse effects: the thrombolytic agents do not distinguish between the fibrin of an unwanted thrombus and the fibrin of a beneficial hemostatic plug. For example, a previously unsuspected lesion, such as a peptic ulcer, may hemorrhage following injection of a thrombolytic agent ure 20. These drugs are contraindicated in patients with healing wounds, pregnancy, history of cerebrovascular accident, or metastatic cancer. Continued presence of thrombogenic stimuli may cause rethrombosis after lysis of the initial clot. Mechanism of action: Alteplase has a low affinity for free plasminogen in the plasma, but it rapidly activates plasminogen that is bound to fibrin in a thrombus or a hemostatic plug. This contrasts with streptokinase, which acts on free plasminogen and induces a general fibrinolytic state. Therapeutic uses: Alteplase is approved for the treatment of myocardial infarction, massive pulmonary embolism, and acute ischemic stroke. Alteplase seems to be superior to streptokinase in dissolving older clots and, ultimately, may be approved for other applications.

Intravenous fluid infused rapidly or given as a bolus should be dextrosefree because maternal hyperglycemia can occur definition of no cholesterol purchase prazosin with visa. Narcotics should be avoided if their peak action will not have diminished bythetimeofdelivery cholesterol test ratio results discount prazosin 2.5mg visa. Contraindications include infection in the lumbar area safe cholesterol levels nz order on line prazosin, clotting defect cholesterol in eggs good or bad prazosin 2.5 mg fast delivery, activeneurologicdisease, sensitivitytotheanesthetic, hypovolemia, and septicemia. Risks include hypotension, respiratory arrest, toxic drug reaction, and rare neurologic complications. Before the epidural is initiated, the patient is hydrated with 5001000 mL of dextrosefree intravenous fluid. Labor and Delivery Admitting Orders Admit: Labor and Delivery Diagnoses: Intrauterine pregnancy at weeks. Condition: Satisfactory Vitals: q1 hr per routine Activity: May ambulate as tolerated. Asthemultiparouspatientapproachescompletedilatationor as the nulliparous patient begins to crown the fetal scalp, preparations are made for delivery. The mother is usually placed in the dorsal lithotomy position with left lateral tilt. The fetal head is delivered by extension as the flexed head passes through the vaginal introitus. Once the fetal head has been delivered, external rotation to the occiput transverse position occurs. A finger is passed into the vagina along the fetal neck to check for a nuchal cord. If shoulder dystocia is anticipated, the shoulders should be delivered immediately. Episiotomy consists of incision of the perineum, enlarging the vaginal orifice at the time of delivery. If indicated, an episiotomy should be performed when 34 cm of fetal scalp is visible. With adequate local or spinal anesthetic in place, a medial episiotomy is completed by incising the perineum toward the anus and into the vagina. Application of pressure at the perineal apex with a towelcovered hand helps to prevent extension of the episiotomy. Delivery of the anterior shoulderisaccomplishedbygentledownward traction on the fetal head. The placenta usually separates spontaneously from the uterine wall within 5 minutes of delivery. Gentle fundal massage and gentle traction on the cord facilitates delivery of the placenta. Time of birth, type of birth (spontaneous vaginal delivery), position (left occiput anterior). Routine Postpartum Orders Transfer: To recovery room, then postpartum ward when stable. A first degree perineal laceration extends only through the vaginal and perineal skin. Repair: Place a single layer of interrupted 3O chromic or Vicryl sutures about 1 cm apart. A second degree laceration extends deeply into the soft tissues of the perineum, down to , but not including, the external anal sphincter capsule. Reapproximate the superficial layers of the perineal body with a running suture extending to the bottom of the episiotomy. Suture the vaginal mucosa with running, interlocking, 3O chromic or Vicryl absorbable suture. Identify each severed end of the external anal sphincter capsule, and grasp each end with an Allis clamp. Proximate the capsule of the sphincter with 4 interrupted sutures of 2O or 3O Vicryl suture, making sure the sutures do not penetrate the rectal mucosa. The laceration extends through the perineum, anal sphincter, and extends through the rectal mucosa to expose the lumen of the rectum. Place a second layer of running suture to invert the first suture line, and take some tension from the first layer closure. Identify and grasp the torn edges of the external anal sphincter capsule with Allis clamps, and perform a repair as for a thirddegree laceration. Fetal heart rate monitoring can significantly reduce the risk of newborn seizures (relative risk 0. The fetus normally tolerates contractions without difficulty, but if the frequency, duration, or strength of contractions becomes excessive, fetal hypoxemia may result. The development of decreased variability in the absence of decelera 246 Fetal Heart Rate Monitoring tions is unlikely to be due to hypoxia. Accelerations are common periodic changes, which are usually associated with fetal movement. These changes are reassuring and almost always confirm that the fetus is not acidotic. Variable decelerations are associated with cord compression, and they usually coincide with the timing of the uterine contractions. Variable decelerations are caused by umbilical cord compression, and theyarethemostcommondecelerationsseeninlabor. Persistent variable decelerations to less than 70 bpm lasting more than 60 seconds are concerning. Variable decelerations with a persistently slow return to baseline are nonreassuring because they reflect persistent hypoxia. Nonreassuring variable decelerations are associated with tachycardia, absence of accelerations, and loss of variability. They are usually shallow (1030 beats per minute), and they reach their nadir after the peak of the contraction. Late decelerations occur when uterine contractions cause decreased fetal oxygenation. Early decelerations are shallow and symmetrical with a pattern similar to that of late decelerations, but they reach their nadir at the same time as the peak of the contraction. These decelerations occur in the active phase of labor and are benign changes caused by fetal head compression. Thedegreetowhichsuchdecelerationsarenonreassuringdependson their depth and duration, loss of variability, and the frequency and progression of recurrence. Attempt to correct the pattern by correcting the primary problem or by institutingmeasuresaimedatimprovingfetaloxygenationandplacental perfusion. Excessiveuterinecontractions, maternalhypotension, or maternal hypoxemia should be corrected. A pelvic examination is performed to rule out umbilical cord prolapse or rapid descent of the fetal head. If no causes are found, umbilical cord compression is likely to be Fetal Heart Rate Monitoring 247 responsible. Maternal oxygenation may be increased by giving oxygen at a flow rate of 810 L/min with a tightfitting face mask. In the supine position, the vena cava and aortoiliac vessels are compressed by the gravid uterus. This results in decreased return of blood to the maternal heart, leading to a fall in uterine blood flow.

In some instances when the incidence varies between genders cholesterol qr order 5 mg prazosin amex, ethnicity cholesterol levels when breastfeeding buy line prazosin, or race this information was noted as well cholesterol medication recall generic 2.5 mg prazosin otc. For certain diseases with insufficient data on either incidence or prevalence cholesterol test eastbourne order prazosin us, other terms, such as rare or unknown were used. The reader is cautioned to use this information only as an indicator of disease prevalence. For example, Grade 1B implies strong recommendation based on moderate quality evidence, whereas 2C refers to weak recommendation based on low or very low quality evidence. Some categories have additional information to further specify a subgroup of patients for whom the category was assigned. F this section lists the number of patients reported in the literature who were treated with therapeutic apheresis. The number of randomized controlled trials and the total number of patients studied. For example, 4(250) indicates that there were four randomized controlled trials with 250 enrolled patients. The minimum requirement for these studies was randomization to a control arm and a test arm. Example: Two randomized studies with 50 patients in each arm and one randomized study with 75 patients in each arm will be denoted as 3(350). Example: 4(56) implies that there were four case series with the total number of reported patients of 56. The committee decided that if the report has not been published in peer reviewed literature within five years it will not be included in the total number of case reports. L the strength of evidence was assigned based on the grading system used by the University HealthCare Consortium as discussed in the text. Typically, this entry contains information on clinical signs and symptoms, pathophysiology, typical presentation and the severity of the disease. N this section provides brief description of therapeutic modalities available to treat the disease. In addition, for some entities the management of standard therapy failure is discussed. O this section discusses a rationale for therapeutic apheresis as well as supporting evidence of its use. P this section briefly describes technical suggestions relevant to the treated disease, which the committee believed were important to improve quality of care or increase chances of positive clinical outcome. Not all diseases have specific technical notes; in such instances a general statement referring to the introductory text is provided. The frequency is based on the data from the published reports however, due to variability of such reports; the committee suggested what is believed to be the clinically most appropriate frequency. Terms such as plasma or albumin were used to denote the type of replacement fluid. T this section provides basic criteria for discontinuation of apheresis procedures. The committee believes that a thoughtful approach to the patient is required to establish reasonable and scientifically sound criteria for discontinuation of treatment. This section does not replace the need for conversation between treating physician and apheresis physician. V Due to limitation of the space only most germane references were used for each fact sheet. For interested readers additional information can be obtained after perusing the cited references. The design of the fact With very few exceptions the World Wide Web sheet and explanation of information contained is resources that were utilized by the committee mem included in ure 1. This decision was made to minimize the risk densing of available information was required to of sending a reader to resources, which may not be achieve this user friendly format. The references pro available any longer, while at the same time allow vided are not meant to be exhaustive but rather serve ing the subcommittee to periodically review the con as a starting point in a search for more information. However, the recommendation been developed to facilitate accuracy and timely future grade added additional and likely critical dimension to updates for therapeutic apheresis indications. The com evaluation of clinical benefit of the therapeutic aphere mitteebased approach is comprehensive and systematic sis in reviewed diseases. We decided to cess of category assignments was similar to the Fourth use babesiosis as an example to explain the thought Special Issue. The group was asked to review, revise, process with new categories and recommendations. The First, babesiosis was divided into severe and high risk process of developing new indications consisted of four populations in the Fifth Special Issue rather than just steps. Step I created a list of diseases to be severe as it was done in the Fourth Special Issue [2]. The specific disease presentation, then this was added to assigned categories and their respective recommendation the categorization. The higher number of indications is mendation grade were based upon the literature and caused by some diseases having several categories and determined by consensus of all subcommittee members. General Issues to be Considered When Evaluating a New Patient for Initiation of Therapeutic Apheresis General Description Rationale* Based on the established/presumptive diagnosis and history of present illness the discussion could include the rationale for the procedure, brief account of the results of published studies, and patientspecific risks from the procedure Impact the effect of therapeutic apheresis on comorbidities and medications (and vice versa) should be considered Technical issues* the technical aspects of therapeutic apheresis, such as a type of anticoagulant, a replacement solution, a vascular access, and a volume of whole blood processed. The location where the therapeutic apheresis will take place should be also addressed. General Considerations An area of potential concern for the apheresis practi There are new textbooks in the field of apheresis tioner is the replacement fluid used during plasma medicine, which users of the Special Issue may find use exchange. If stated in the fact sheet that plasma exchange ful, including Apheresis: Principles and Practice, Third is performed daily, plasma may be indicated as part of Edition [15]. The format of the Special Issue restricts the replacement fluid to prevent severe coagulopathy from amount information, which can be provided in each fact repetitive removal of coagulation factors through serial sheet. Additionally, maintaining the fibrinogen level included in a consultation note before performing an >100 mg/dL is typically recommended to prevent apheresis procedure. In many instances, plasma sup tion may be helpful to readers, who have less experience plement can be given toward the end of procedure. Also some of the issues related to specific Lastly, issues related to the timing of procedures, diseases are clearly addressed in those disease specific such as emergency (within hours), urgent (within a day), fact sheets, particularly in the technical notes section. Depending upon the removal pore size of the filters used, different components can be removed. We emergently, that is, in the middle of the night if warranted, thought that it would be helpful to apheresis medicine are thrombocytopenic thrombotic purpura, acute chest community to agree on definitions of apheresis proce syndrome in sickle cell disease, thrombocytosis, hyperleu dures. We attempted to summarize definitions of most kocytosis, hyperviscosity, and malaria. These isoag glutinins may cause acute hemolysis of the red cells present in the transplanted stem cell product. These products should be plasmareduced if the titer is >256 when the plasma volume is >200 mL to prevent an acute hemolytic transfusion reaction. T cell depletion and cyclosporineA are risk factors for this com plication, whereas methotrexate reduces this risk by suppressing the proliferation of donor lymphocytes.

As tubular obstruction progresses the decline in renal function becomes irreversible cholesterol chart for seafood order prazosin once a day. Hypotheses regarding the mechanism of pathological distal tubule cast formation focus on an increase in light chain concentration in the distal tubular urine truth about cholesterol in eggs generic prazosin 5mg without a prescription. This may result from the overwhelming of proximal tubule processing of light chains when light chain production is rising due to tumor progression Other con tributing factors may include hypercalcemia cholesterol medication erectile dysfunction purchase prazosin 2.5mg without a prescription, hyperuricemia cholesterol ranges hdl order 5mg prazosin with amex, dehydration, intravenous contrast media, toxic effects of light chains on distal tubular epithelium, etc. Current management/treatment Therapeutic approaches rely on inducing an alkaline diuresis through intravenous administration of normal saline and sodium bicarbonate with or without loop diuretics. Antimyeloma chemotherapy consisting of an alkylating agent with a corticosteroid is used to diminish Mprotein production. More recently, immune modulation (thalidomide, lenalidomide) and proteosome inhibi tion (bortezomib) have emerged as effective therapy. Rationale for therapeutic apheresis Although chemotherapy and alkaline intravenous fluid are the primary modes of therapy, plasma exchange has been used to acutely decrease the delivery of light chains to the renal glomerulus for filtration. Peritoneal dialysis (but not hemodialysis) can also remove light chains but with lower efficiency than plasma exchange. A randomized trial of 21 patients with biopsyproven myeloma kidney (cast nephropathy) who received melphalan, prednisone and forced diuresis with or without plasma exchange showed no statistically significant outcome differences. However, among a dialysisdependent subgroup, 43% in the plasma exchange group and none in the control group recovered renal function. This led to an endorsement of plasma exchange for myeloma kidney by the Scientific Advisors of the International Myeloma Foundation. The largest randomized trial of chemotherapy and supportive care with or without plasma exchange failed to demonstrate that 5 to 7 plasma exchange procedures over 10 days substantially reduces a composite outcome of death, dialysis depend ence or estimated glomerular filtration rate of <30 ml/min/1. This study has called into question the role of plasma exchange in the treatment of myeloma kidney in an era of rapidly effective chemotherapy. On the other hand, this study has been criticized in that most of the enrolled patients were not proven to have cast nephropathy by renal biopsy, confidence intervals were wide, suggesting the study was underpowered, and the com posite outcome undervalued an end result of dialysis independence for many patients. Survival at six months, as opposed to end points more specific to re covery of renal function, has also been questioned as part of the composite outcome. More recent data suggest that plasma exchange has only transient effects on serum free light chains as measured using a clinically available assay. Biopsyproven cast nephropathy may be an important supportive finding if plasma exchange is contemplated. Technical notes Initial management, especially in the case of nonoliguric patients, should focus on fluid resuscitation (2. If serum creatinine remains elevated after several days, consider addition of plasma exchange. All of the published studies combine plasma exchange with chemotherapy and other forms of supportive care described above. Published studies vary with respect to treat ment schedules and replacement fluids employed for plasma exchange. If plasma exchange and hemodialysis are to be performed on the same day, they can beper formed in tandem (simultaneously) without compromising the efficiency of the hemodialysis procedure. Smaller trials have demonstrated improved 1year survival in the groups whose treatment included plasma exchange, the largest, randomized trial did not demonstrate improved survival at six months. In all cases ultimate survival depends on a satisfactory response to chemotherapy. It has also been seen in patients with hepatorenal syndrome and in the perioperative period following liver transplanta tion. It occurs in 2 to 7% of patients with chronic renal failure receiving Gd contrast agents. Additional findings may include hair loss, gastroenteritis, conjunctivitis, bilateral pulmonary infiltrates, and fever. Over 6 to 12 months, the swelling, pruritus, and sensory changes resolve while the skin progresses to a thickened, hardened dermis/subcutis with epidermal atrophy. Fibrosis results in joint contractures leading to wheel chair dependence and may extend into deeper tissues including skeletal muscle, heart, pericardium, pleura, lungs, diaphragm, esophagus, kidneys, and testes. In 5% of patients, the disease progresses rapidly to death within weeks to months while the remaining demonstrate slow progression. Overall mortality rate is 30% with death due to restricted mobility and respiratory insufficiency. The prolonged elimination results in disassocia tion of the Gd, which may be further enhanced by metabolic acidosis. Increased phosphate levels and inflammation leads to Gd phosphate tissue deposition. This is taken up by tissue macrophages resulting in proinflammatory and profibrotic cytokine production leading to tissue infiltration by circulating fibrocytes and collagen production. Current management/treatment Replacement of renal function through renal transplant has been associated with cessation of progression and reversal. Additional therapies which have been used include steroids, imatinib messylate, chelation therapy with sodium thiosulfate, plasma exchange, and extracorporeal photopheresis. Rationale for therapeutic apheresis Due to the lack of an effective therapy, plasma exchange has been applied. Additional reported changes have included decreased swelling, pain, and paresthesias. Additional reported changes have included resolution of skin lesions and decreased pruritis. Improvement of early symptoms in one patient reported to have occurred within 3 days of initiation of treatment. Symptoms of myelitis include paraparesis and sensory loss below the lesion, sphincter loss, dyesthesia, and radicular pain; symptoms of optic neuritis include ocular pain, visual field deficits, and positive phenomena; and symptoms of hypothalamic and brainstem involvement, which occur in 15% of patients, include hiccoughs (hiccups), intractable nausea, and respiratory failure. Monofi phasic course is associated with younger age at disease onset and equal male:female predominance. Description of the disease Drug overdose and poisoning, whether accidental, intentional, or iatrogenic, result from excessive exposure to an agent capable of producing tissue injury and/or organ dys function. It is difficult to quantify the morbidity and mortality attributable to these problems. The majority of incidents is accidental and occurs at home, most often involving children under the age of six. The mechanism of tissue damage varies with the nature of the offending substance and the mode of entrance into the body. Agents may be directly toxic to human tissue or may require enzymatic conversion to an active, injurious metabolite. The physician can choose from a vast array of methods to enhance removal of the toxin, depending on specific characteristics of the agent and the route of exposure. Wholebowel irrigation, another technique available for gastrointestinal decontamination, is particularly useful for removing poorly absorbed agents that are not adsorbed to charcoal. Forced acid or alkaline diuresis is used to promote the renal elimination of ionized agents that are not strongly bound to proteins. Hemodialysis is an effective technique for removing drugs that are not tightly bound to plasma proteins and that readily diffuse through a semi permeable membrane. Hemoperfusion, a procedure in which blood is passed directly over sorbent particles, can be more effective than dialysis for proteinbound drugs and large molecules. Comprehensive lists of drugs and chemicals removed with dialysis and hemoperfusion have been compiled. The clinical benefit can be achieved only if toxin levels can be reduced to concentrations below the threshold for tissue damage. Reports of the successful use of apheresis in the treatment of various drug over doses and poisonings are generally anecdotal. There are also case reports of the failure of plasma exchange to remove substances bound to proteins and lipids such as barbiturates, chlordecone, aluminum, tricyclic antidepressants, benzodiazipines, quinine, and phenytoin. Very early initiation of the treatment (less than 30 hours) resulted in the best outcomes. There are anecdotal reports on the use of immunadsorption to treat poisoning with toxins such as botulin toxin. There is increasing number of biological drugs such as monoclonal antibodies (pharmacokinetic halflife typically 10 to 30 days with potentially longer pharmacody namic halflife) with rare but potentially serious side effects.

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