Most Effective Kidney Damage Treatments
The relation between long-term heavy exposure to analgesics and the risk of chronic renal disease has been the object of intensive toxicological and epidemiological research for many years (SEDA-24, 120 1R). Most of the earlier reports suggested that phenacetin-containing analgesics probably cause renal papillary necrosis and interstitial nephritis. In contrast, there is no convincing epidemiolog-ical evidence that non-phenacetin-containing analgesics (including paracetamol, aspirin, mixtures of the two, and NSAIDs) cause chronic renal disease. Moreover, findings from epi-demiological studies should be interpreted with caution, because of a number of inherent limitations and potential biases in study design (2r). Two recent methodologically sound studies have provided more information on this topic.
Anemia may occur in patients with chronic renal failure as the result of the inability of the kidney to produce ery-thropoietin. Erythropoietin is a glycoprotein hormone synthesized mainly in the kidneys and used to stimulate and regulate the production of erythrocytes or red blood cells (RBCs). Failure to produce the needed erythrocytes results in anemia. Two examples of drugs used to treat anemia associated with chronic renal failure are epoetin alfa (Epogen) and darbepoetin alfa (Aranesp).
Perfusion Ringer (PR) Dialysis fibers are perfused with isotonic solution, the composition of which should resemble as much as possible the composition of brain extracellular fluid. Because fluid composition in each specific brain area is unknown and subject to time variations, PR composition has been validated on the base of its capacity to cause minimal alteration of brain function in that specific brain area, being compatible with voltage-responsive and calcium-dependent neurotransmitter release. The composition of PR used in our most recent investigations is 147 mMNaCl, 2.2 mM CaCl2, 4 mMKCl. It can be pumped through the dialysis probe at a constant flow of 1 pL min. The rationale of ionic composition of PR has been debated in several articles (5,6). The most critical ions in the PR composition are K+ and Ca2+. The former is critical because its presence in the PR may alter physiological depolarization of terminals, with a consequent change in neurotransmitter release. Experiments...
Renal papillary necrosis has been reported after long-term intake or abuse of aspirin and other NSAIDs (SEDA-11, 85) (SEDA-12, 79). The relation between long-term heavy exposure to analgesics and the risk of chronic renal disease has been the object of intensive toxicological and epidemiological research for many years (SEDA-24, 120) (70). Most of the earlier reports suggested that phenacetin-containing analgesics probably cause renal papillary necrosis and interstitial nephritis. In contrast, there was no convincing epidemiological evidence that non-phenacetin-containing analgesics (including paracetamol, aspirin, mixtures of the two, and NSAIDs) cause chronic renal disease. Moreover, findings from epidemiological studies should be interpreted with caution, because of a number of inherent limitations and potential biases in study design (71). Two methodologically sound studies have provided information on this topic. How can we explain the contrasting results of these two studies A...
The results of two trials in patients with chronic nephropathy have reinforced the benefit of ACE inhibitors in slowing the progression of chronic renal insufficiency due to renal diseases other than diabetic nephropathy (13-15) and have provided sufficient information on the safety profile of these agents in chronic renal insufficiency. This was found to be essentially the same as in patients with normal renal function. The current practice of avoiding ACE inhibitors in severe renal insufficiency, to prevent further renal impairment and hyperkalemia, is no longer justified, although careful monitoring should still be observed. The Ramipril Efficacy in Nephropathy (REIN) trial was designed to test whether glomerular protein traffic, and its modification by an ACE inhibitor, influenced disease progression in non-diabetic chronic nephropathies (13). Patients were stratified before randomization by 24-hour proteinuria. Treatment with ramipril or placebo plus conventional antihypertensive...
Semipermeable membranes of tubular types are usually used for extraction of low-molecular compounds by dialysis. Typically, a volume of crude specimen fluid is packed in a membrane tube, which is then put in a large volume of an organic solvent in a beaker with stirring of a Teflon-coated magnet bar. Since the movement of a drug stops, when an equilibrium is attained between the inner and outer solutions, complete recovery cannot be achieved by a single extraction. Although the handling procedure itself is very simple, it takes a long time to reach the equilibrium according to the kind of a target compound this method is not suitable for treatments of many specimens.
This is a modification of the earlier push-pull cannula which could be used in anaesthetised animals only. The microdialysis probe which has an outside diameter of about 250 pm (Fig. 4.6) is implanted into the brain under anaesthesia and then subsequently perfused with aCSF. Solutes (including neurotransmitters) in the extracellular fluid of the brain diffuse down their concentration gradient into the probe. By taking samples of the effluent dialysate at regular intervals it is possible to monitor changes in transmitter release. This technique has been used for several years to study release of monoamines (e.g. Sharp, Umbers and Gartside 1997) but is now used to harvest acetylcholine and amino acids as well. Since the molecular cut-off of the dialysis membrane is in the region of 6-20 kDa (depending on the type of membrane used), this technique can also be used to measure release of some small neuropeptides (e.g. oxytocin and vasopressin). Figure 4.6 The tip of a microdialysis probe,...
Depending on the criteria used, the incidence of aspirin hypersensitivity is variously estimated as being as low as 1 or as high as 50 , the highest frequency being found in asthmatics. The condition is characterized by bronchospasm (asthma), urticaria, angioedema, and vasomotor rhinitis, each occurring alone or in combination, often leading to severe and even life-threatening reactions. There is no clear evidence of an association with tumors, apart from the possible peripheral contribution of aspirin to the development of urinary tract neoplasms in patients with analgesic nephropathy. Indeed, some authors have suggested a role for salicylates in reducing the incidence of color-ectal tumors and breast tumors.
A cumulative drug effect may be seen in those with liver or kidney disease because these organs are the major sites for the breakdown and excretion of most Patients with liver or kidney disease are usually given drugs with caution because a cumulative effect may occur. When the patient is unable to excrete the drug at a normal rate the drug accumulates in the body, causing a toxic reaction. Sometimes, the primary health care provider lowers the dose of the drug to prevent a toxic drug reaction.
Neurotoxicity secondary to aciclovir is rare and is associated with high plasma concentrations (SEDA-18, 299), such as result from impaired renal function (9). Although the risk is greatest with intravenous administration, neurotoxicity has previously been noted with oral use. A 59-year-old woman on hemodialysis was treated with oral aciclovir 200 mg day for ophthalmic Herpes zoster. After a few days, an ophthalmic aciclovir cream was started (one application every 6 hours) because of ipsi-lateral Herpes keratitis. After 1 week of combined oral and topical treatment, she became confused, with dys-arthria and audiovisual hallucinations. Aciclovir was withdrawn and hemodialysis was initiated. Complete resolution of symptoms was achieved after three hemo-dialysis sessions in 3 days. Aciclovir plasma concentrations before hemodialysis were high (45 mmol l) and fell rapidly during hemodialysis.
The serum concentration of a particular drug is determined by absorption, distribution, metabolism, and excretion of a drug. Major characteristics that affect serum drug concentrations include genetic make up of a patient as well as age, gender, weight, habits (such as smoking), and diet. Elderly and newborns may metabolize a particular drug more slowly than others. Some drugs, for example theophylline, distributes to lean weight only where other drugs, such as phenytoin, distributes to total weight. Diseases may alter serum drug concentrations dramatically. Hepatic disease may alter metabolism of a drug where a patient with renal failure may clear a drug in urine more slowly than a patient with normal renal function. Pregnancy alters metabolism of several drugs while drug-drug interactions may also significantly alter serum drug concentrations.
Contamination of albumin solutions with aluminium and consequent toxic effects have been described (18). Analysis of albumin from 20 suppliers showed aluminium contents varying from 1.03 to 1301 mmol l depending on the batch and the manufacturer (19). Aluminium overloading is especially likely to occur in patients with impaired renal function who receive large volumes of albumin, leading to osteodystrophy and encephalopathy (20). An Austrian manufacturer of human albumin 20 and 25 voluntarily recalled the products because the phar-macopoeial specification for aluminium (200 ng ml or less) for treatment of premature infants and dialysis patients cannot be guaranteed over the whole shelf life of 3 years when stored at temperatures above 8 C (21).
The systemic availability of aluminium is normally very low, because the gastrointestinal tract, skin, and lungs are excellent barriers to its entry furthermore, the small amounts that pass these barriers are efficiently eliminated by the kidneys. However, problems can arise if the natural protective barriers are bypassed or if there is impaired renal function. Significant systemic effects are rare unless there is a high degree of absorption. Aluminium is toxic in patients on chronic hemodialysis and peritoneal dialysis and in those taking oral aluminium-containing medications. Aspects of aluminium safety (9) and metabolism (10) have been reviewed. The association between aluminium in drinking water and Alzheimer's disease continues to be discussed and remains controversial (11).
In many patients with severe renal disease there is a double risk they are exposed to aluminium as a part of their treatment (in agents given for the control of serum phosphate concentrations, in aluminium-containing dialysis fluids and, in one case, in the form of bladder irrigation with alum) (66), and at the same time they have a reduced ability to eliminate it. Aluminium-containing phosphate binders are especially risky if used in combination with an alkalinizing citrate solution (Shohl's solution) (67,68) due to the formation of an aluminium citrate complex in the gastrointestinal tract, aluminium is absorbed more readily. In addition, aluminium citrate complex has a synergis-tic inhibitory action on bone growth and thus exacerbates aluminium-associated osteomalacia in chronic renal failure. Children with impaired renal function may be particularly susceptible to aluminium intoxication solely from oral aluminium loading (69). When aluminium is used as a phosphate binder in...
The main adverse reactions of aminoglycosides consist of kidney damage (often presenting as non-oliguric renal insufficiency) and ototoxicity, including vestibular and or cochlear dysfunction. Neuromuscular transmission can be inhibited. Hypersensitivity reactions are most frequent after topical use, which should be avoided. Anaphylactic reactions can occur. Tumor-inducing effects have not been reported.
Minimally effective serum total phenytoin concentration is considered as 10 g mL, whereas the upper end of the therapeutic range is 20 g mL. Carbamazepine is an iminostilbene derivative structurally similar to the TCA imipramine. It was approved in the USA in 1974 as an antiepileptic for many seizure disorders and in 1979 for use in children over 6 years of age. The current uses of carbamazepine include partial seizures with complex symptomatology, generalized tonic-clonic seizures, and mixed seizures. Carbamazepine and phenytoin are considered as the drugs of choice for treating these seizure disorders (108). Carbamazepine is also frequently added to the existing TCA therapy (109). Carbamazepine, like lithium, may help some individuals with episodic behavioral dysfunction, such as loss of control and aggression, even in the absence of epileptic, affective, or organic features (110,111). TCA and anticonvulsants are also used in the treatment of pain in polyneuropathy (112). The...
ACE inhibitors can cause hyperkalemia because they inhibit the release of aldosterone. The effect is usually not significant in patients with normal renal function. However, in patients with impaired kidney function and or in patients taking potassium supplements (including salt substitutes) or potassium-sparing diuretics, and especially aldosterone antagonists, hyperkalemia can occur. In two cases, hypoaldosteronism with diabetes was implicated (53,54).
Aminoglycosides are poorly absorbed from the gastrointestinal track, and these drugs are administered intravenously or intramuscularly. The major route of elimination is through the kidney where 85-95 of the drugs are recovered unchanged. Patients with impaired renal function have lower aminoglycoside elimination rates and longer half-lives compared with patients with normal renal function. Moreover, elimination of aminoglycosides is slower in elderly patients, and many patients require prolonged dosing interval. Children have a higher clearance of aminoglycosides. Siber et al. reported that after 1 mg kg dose of gentamicin, the mean peak plasma concentration was 1.58 g mL in children with age between 6 months and 5 years, 2.03 g mL in children between 5 and 10 years, and 2.81 g mL in children older than 10 years. Patients with fever showed shorter half-life and lower plasma concentrations of gentamicin (139).
Akhlaghi used equilibrium dialysis technique to determine the Fu of cyclosporine. The authors used radioactive 3H cyclosporine purified by HPLC for this purpose. Equilibrium dialysis experiments were performed using a Spectrum equilibrium dialysis apparatus and cellulose dialysis membrane (SpectraPor 2, Spectrum Medical Instrument, Los Angeles, CA) with a molecular weight cut-off of 12,000-14,000. To avoid non-specific binding of cyclosporine to surfaces of the dialysis cell, original cells were replaced with cells constructed from medical grade stainless steel and having volume of 1.36 ml per half-cell. For the equilibrium dialysis experiment, 1 ml of plasma was supplemented with 3H cyclosporine and then dialyzed against isotonic phosphate buffer at 37 C for 18 h. After dialysis, aliquots of plasma and buffer were removed simultaneously using two glass syringes and radioactivity of specimens was measured using liquid scintillation counter. The volume shift was determined from total...
The mean free plasma-unbound amprenavir concentration was 8.6 (range 4.420 ) in one study. Moreover, lopinavir was able to displace amprenavir from protein binding in vitro, but another strongly protein-bound protease inhibitor ritonavir had no effect (35). Boffito et al. studied lopinavir protein binding in vivo through a 12-h dosing interval and measured free lopinavir concentrations using HPLC-MS MS. The mean unbound lopinavir concentration was 0.92 when measured using ultrafiltration but 1.32 using equilibrium dialysis. The unbound percentage of lopinavir was also
The subclass Hamamelidae consists of 11 orders and 24 families, and about 3400 species of plants which are thought to have originated from some tan-niferous Magnoliidae, forced to adapt to a climate of alternating wet and dry seasons in the Upper Cretaceous (Appendix I). These are mostly trees, the flowers of which are tiny, packed in spikes, unisexual, with distinct carpels, and adapted to wind pollination. In this Subclass, the use of alkaloids as chemical weapons has dramatically declined with the advent of tannins and flavonoids. The mechanisms by which tannins impede microbial infestation are enzyme inhibition, substrate deprivation, action on membranes, and metal ion deprivation. When consumed by mammalian, tannins form complexes with salivary glycoproteins and rend the plant unpalatable. Levels of tannins above 5 of the diet induce hemorrhagic gastroenteritis, necrosis of the liver, and kidney damage with proximal tuberal necrosis and death. Proanthocyanidins or condensed...
RISK FOR INEFFECTIVE TISSUE PERFUSION RENAL. When the patient is taking a drug that is potentially toxic to the kidneys, the nurse must carefully monitor fluid intake and output. In some instances, the nurse may need to perform hourly measurements of the urinary output. Periodic laboratory tests are usually ordered to monitor the patient's response to therapy and to detect toxic drug reactions. Serum creatinine levels and BUN levels are checked frequently during the course of therapy to monitor kidney function. If the BUN exceeds 40 mg dL or if the serum creatinine level exceeds 3 mg dL, the primary health care provider may discontinue the drug therapy or reduce the dosage until renal function improves.
P falciparum and P. malariae infections are clearly associated with renal disease. Moderate proteinuria is a common finding (Ehrich and Horstmann 1985) and usually resolves following parasite eradication. In severe disease, a nephrotic syndrome, and less frequently, acute renal failure may develop as a consequence, and arises from a combination of impaired microcirculation due to parasite obstruction of the microvasculature, hypovolaemia, haemolysis, and intravascular coagulation. In a proportion of cases, quartan malaria is associated with nephrotic syndrome as a life-threatening complication in children in endemic areas. A membranoproliferative type of glomerulonephritis with focal and segmental glomerulosclerosis is the most common type of renal damage (Van Velthuysen and Florquin 2000). A combination of endothelial damage and immune complex deposition is observed, but it has been found that immune complexes containing malarial antigens represent only a fraction of the glomerular...
Interactions of transfusion with transplantation can occur (200). Blood transfusions, and especially donor-specific transfusions, given before kidney transplantation have beneficial effects on graft survival the mechanism for this is not known (201-203). By contrast, pre-transplant transfusions in bone marrow recipients with aplastic anemia cause major complications, and can be responsible for graft rejection and marrow transplantation failure (204).
Icodextrin in the dialysis fluid in continuous ambulatory peritoneal dialysis can contribute to overestimation of blood glucose (SEDA-26, 461). In a comparison of a meter using the glucose oxidation method and a meter using the glucose dehydrogenase method, only the former gave results that were comparable with the laboratory method (3). The authors concluded that meters must be cross-checked with the laboratory before they can be used to measure blood glucose in patients in contact with icodextrin.
The effects of renal insufficiency on the pharmacokinetics of cardiac glycosides have been reviewed (146). The most important effect of renal failure is a reduced rate of elimination of digoxin, leading to increased accumulation during steady-state treatment. The same applies to some other glycosides, including beta-methyldigoxin, beta-acetyldigoxin, ouabain, and k-strophanthin, but not to glycosides that are mostly metabolized, such as digitoxin, the proscillaridins, and peruvoside (4). Drug interactions can also lead to reduced digoxin renal elimination.
Doses gastrointestinal distress may occur, and persons suffering from stomach irritation are supposed to avoid the compound. A case report notes a deliberate overdose that destroyed part of a patient's stomach. Heart attack has occurred from chloral hydrate overdose, but that is unusual. In high quantities the compound interferes with heart rhythm and reduces blood pressure and breathing seizures are possible. Experiments using chloral hydrate on rats and mice have injured the liver, and inhaling the drug's vapor has caused lung damage in mice. Human physical contact with the compound can irritate the skin, lungs, and eyes. The substance is suspected of causing kidney damage and colon cysts and of aggravating a disease called porphyria. Reduction may occur in the number of white blood cells. Although the substance is a depressant, some persons are stimulated by the drug.
In renal failure as well as damage to kidney or urinary pathways, the heme or its derivatives may be present in urine, generating hemolytic interference similar to that of serum. Urine may also have interference from myoglobin, the oxygen-binding protein in striated micelles, also containing the heme group. Whereas hemoglobin is a tetramer of the heme and globin complex, myoglobin is a monomer and, consequently, is smaller than hemoglobin by three-fourths. Thus, when there is injury to skeletal or cardiac muscle, myoglobin may be released and then excreted in urine (myoglobinuria). Under such condition, urine samples have a color similar to that of a cola drink or black coffee and show interference similar to that of hemolysis in serum.
Maternal azathioprine treatment during pregnancy is clearly teratogenic in animals, but the mechanisms are not known. A large number of reports have described the outcome of pregnancies following the use of immuno-suppressant drugs, in particular in renal transplant patients, and hundreds of pregnancies have been analysed (199). The largest experience is that derived from the National Transplantation Pregnancy Registry which has been built up in the USA since 1991 (200). This registry has accumulated data on more than 900 pregnancies, of which 83 followed kidney transplantation and in this and other studies there was no difference in the rate of malformations when comparing ciclosporin with other immunosuppressive regimens (197,198,201). Ectopic pregnancies and miscarriages seemed to occur at a similar rate as in the general population. The most common complications were frequent prematurity and more frequent intrauterine growth retardation with low birth-weight. Risk factors...
These drugs are used with caution in patients with tachycardia, cardiac arrhythmias, hypertension, hypotension, those with a tendency toward urinary retention, those with decreased liver or kidney function, and those with obstructive disease of the urinary system or gastrointestinal tract. The anticholinergic drugs are given with caution to the older adult.
Digoxin is a cardiac glycoside, and after the discovery of endorphins, the endogenous equivalent of opiates, there was a hypothesis for the presence of an endogenous equivalent of cardiac glycosides. It was further hypothesized that anti-digoxin antibody may be able to detect the presence of DLIS in body fluids. Gruber et al. (4) first demonstrated the presence of endogenous DLIS in 1980, in volume-expanded dogs. Then Craver and Valdes reported an unexpected increase in serum digoxin concentration in a renal failure patient who was taking digoxin. Apparent serum digoxin level was still
Although an important step, the Pure Food and Drug Act did not fully protect the public health. In particular, events in the late 1930s brought the issue of drug safety into sharp focus. A sulfanilamide preparation, considered a true breakthrough in medical treatment, had been developed as a systemic anti-infective, but because it proved difficult to administer the new preparation to children in capsule form, a new formulation was created by dissolving the drug in diethylene glycol, better known today as antifreeze. The formulation was tested for its ability to be administered effectively but not for its safety, and as a result, more than a hundred people lost their lives from kidney failure before the toxic nature of the solvent was recognized. While none of this was due to the sulfa drug itself, it led to the passage of the federal Food, Drug, and Cosmetic Act of 1938. This law
Volume expansion is a major cause of elevated DLIS in blood. Elevated concentrations of DLIS have been reported in uremia, essential hypertension, hypertension of water volume expansion, liver disease, preeclampsia, liver and kidney transplant, congestive heart failure, premature babies, and other conditions (19-24).
The Fab fragment of antidigoxin antibody is commercially available as Digibind and DigiFab. Digibind has been available in the USA since 1986 (Glaxo Wellcome Inc.), and more recently in 2001, the Food and Drug Administration of the USA approved DigiFab for treating potentially life-threatening digoxin toxicity or overdose. Digibind is produced by immunizing sheep with digoxin followed by the purification of the Fab fragment from blood, whereas DigiFab is prepared by injecting sheep with digoxindicarboxymethylamine followed by purification of fab fragment. The molecular weight of DigiFab (46,000 Da) is similar to that of Digibind (46,200 Da). The approximate dose of Fab fragment is 80 times the digoxin body burden (in mg), or if neither the dose ingested nor the plasma digoxin concentration is known, then 380 mg of Fab fragment should be given. The half-life of the Fab fragment in humans is 12-20 h, but this may be prolonged in patients with renal failure (63). The Fab fragment is also...
Anaphylaxis as an adverse effect of hemodialysis has been analysed from records of about 260 000 courses of dialysis treatment, at three centers. There were 21 severe reactions over the 10.5-year period of the survey, all highly suggestive of anaphylaxis (2). Reactions occurred within minutes of initiating dialysis and were characterized by cardiopulmonary, mucocutaneous, and or gastrointestinal tract symptoms. Four respiratory arrests occurred and there was one death. When the individual histories and treatments were analysed, there was strong evidence that hollow-fiber dialysers made of cuprammonium cellulose were responsible. No obvious factors could be found to identify predisposed patients suboptimal rinsing of the cuprammonium cellulose hollow-fiber dialysers before use may have been responsible for some of the reactions. Repeated dialysis anaphylaxis in one patient has been reported (3).
Prostaglandins regulate renin-angiotensin secretion and thus glomerular filtration rate and sodium homeostasis. These effects appear to be COX-2 driven (315). The kidney is a rare organ, one that expresses COX-2 under non-pathological situations. Expression in the loop of Henle apparently drives prostaglandin formation in the kidney and the subsequent physiological responses. Thus a selective agent would likely have similar negative effects on kidney function as those of the nonselective NSAIDs. This is apparently the case with both Vioxx and Celebrex (315).
Minocycline and doxycycline are predominantly eliminated by the liver and biliary tract (70-90 ). Therefore, no change in dose is needed in patients with impaired renal function. However, it should be considered that hepatic elimination of doxycycline or minocycline might be accelerated by co-administration of agents that induce hepatic enzymes.
(Maitland et al. 2003), but others have recently shown insignificant depletion of total water in children presenting with severe malaria (Planche et al. 2004 for a review see chapter by T. Planche et al., this volume). However, the majority of children presenting with respiratory distress are severely anaemic, have a metabolic acidosis secondary to reduced oxygen carrying capacity and respond to rapid transfusion of fresh blood (for review see English et al. 1996). A minority of those with respiratory distress do not respond to appropriate resuscitation they probably represent a heterogeneous clinical group and may have renal failure, systemic bacterial infection or a more profound syndrome of systemic disturbance due to malaria parasites.
Angina is a common problem in older adults. When an older adult requires an antianginal drug, the dosage may be reduced to compensate for impaired renal function or heart disease. Older patients are at increased risk for postural hypotension. Blood pressure and ability to ambulate should be monitored closely.
Epoetin causes or aggravates hypertension in about 20-35 of dialysis patients (56-60). It can be accompanied by encephalopathy or seizures (61). In 44 children with chronic renal insufficiency treated with epoetin 150 U kg week, hypertension was mostly observed in patients on hemodia-lysis (66 ) compared with peritoneal dialysis (33 ) and predialysis patients (16 ) (62). During an open, uncontrolled study in 22 patients with end-stage renal disease treated with epoetin omega there was one case of hypertensive encephalopathy (70). One of the possible mechanisms of epoetin-induced hypertension is an imbalance of local endothelial factors, such as endothelium-derived relaxation factor and endothelin (61), a potent vasoactive peptide produced by endothelial cells (13), increased concentrations of which have been observed in adults with an increase in mean blood pressure of more than 10 mmHg. In contrast, in preterm infants receiving epoetin there were no acute effects of epoetin on...
Epoetin can be administered in four ways intravenously, subcutaneously, orally, and intraperitoneally (37). The subcutaneous route is preferred in patients undergoing dialysis, because subcutaneous epoetin provides better long-term utilization and maintains the same hematocrit with 20 lower dosages than intravenous administration. After intraperitoneal administration the absorption time is prolonged and only 5-10 of the dose is utilized (37). Local reactions occur at the site of injection when epoetin is given subcutaneously (117), and local pain has been reported after the administration of citrate- or phosphate-buffered epoetin (117,118). In children undergoing peritoneal dialysis, epoetin is usually given intraperitoneally, resulting in similar systemic availability and dosages compared with subcutaneous administration. A follow-up study is required to determine if the risk of peritonitis is increased by intra-peritoneal epoetin (120).
In women the drug is used to fight breast cancer by interfering with hormones that encourage the disease. Research has found fluoxymesterone effective in reducing a cancer called myeloma and for counteracting anemia caused by myeloma. Mixed results have occurred when using the drug for correcting anemia associated with kidney failure. The substance has been a treatment for osteoporosis, a condition in which bones become susceptible to easy breakage, and for hereditary angioedema an affliction that may involve throat swelling that interferes with breathing.
Freon may produce lung spasms. The substance has caused high blood pressure, perhaps as a consequence of kidney damage resulting from the substance. Users have described accelerated heartbeat. Inhalation has also brought on a cardiac emergency called ventricular fibrillation, which is fatal without immediate medical intervention. Even if the person survives, most individuals do not receive sufficient help in time to prevent lasting brain injury from lack of oxygen. In one case a 15-year-old freon user not only experienced the heart emergency but suffered lung and muscle damage as well. Using enough freon in a closed space can be fatal due to oxygen starvation. Inhalers have also reported injuries ranging from lacerations to a broken neck when they lost consciousness and collapsed while sniffing freon such harm may not be attributable to the substance itself but can be a consequence of using it.
Some two and a half years ago, we developed an Institutional Review Board (IRB)-approved protocol for the assessment of free drug concentrations by measuring both the saliva and the free drug in plasma utilizing the same tandem mass spectrometric methods for plasma or serum measurement as reported earlier. Our specified sample is either plasma or serum, as the methods we published previously work equally well on both. We, however, inject a bigger sample for the free drug measurement (50 vs. 10 L for plasma serum). Free drug concentrations can be measured by using either equilibrium dialysis or, more commonly, devices with molecular cutoff filters such as the Amicon Centrifree micropartition system (Millipore Corporation, Bedford, MA) or the Worthington Diagnostics ultrafree system (Worthington, Jacksonville, FL). Plasma ultrafiltrate is obtained by centrifuging 1 mL of plasma in Amicon system and
The use of fluconazole in 726 children under 1 year of age, reported in 78 publications, has been reviewed (64). They received a wide range of dosages for up to 162 days. Fluconazole was well tolerated and efficacious in the therapy of systemic candidiasis and candidemia in children under 1 year of age, including neonates and very low birth-weight infants. The daily dosage recommended by the manufacturers is 6 mg kg, to be reduced in patients with impaired renal function in accordance with the guidelines given for adults.
The drug is given three times weekly IV or SC, or if the patient is receiving dialysis, the drug is administered into the venous access line. The drug is mixed gently during preparation for administration. Shaking may denature the glycoprotein. The vial is used for only one dose any remaining or unused portion is discarded.
Garcia, age 54 years, has chronic renal failure. He undergoes dialysis three times a week. The physician orders epoetin alfa to be administered. Discuss the preadministration and ongoing assessments for Mr. Garcia. During a discussion with you, Mr. Garcia asks why he is receiving this drug. Discuss how you would answer Mr. Garcia's question.
In a renal dialysis unit, five of 28 members of the staff had respiratory symptoms associated with formaldehyde, and in two cases, attacks of wheezing could be provoked by exposure to formaldehyde. One nurse was particularly affected, the asthmatic wheeze persisting for 8 days after exposure (7).
Trastuzumab is a monoclonal antibody which blocks the human epidermal growth factor 2 protein and has an estimated half-life of 12 days. Waterstone (2006) reported on an uneventful prcgnancy and the delivery of a healthy girl whose mother conceived 3 days after her second cyclc of trastuzumab. There is one case report of inadvertent exposure of a 28-year-old with breast cancer who was given the drug every 3 weeks until week 20 of her pregnancy. When, in week 23, the pregnancy was noticed, a lack of amniotic fluid prevailed with a healthy female fetus. Gradually, Lhe amount of amniotic fluid recovered. In week 37, a healthy girl was delivered whose kidney function was normal at the age of 6 months and who showed no sign of pulmonary hypoplasia (Watson 2005). There is another report regarding the development of an oligohydramnios after trastuzumab therapy. Fanale (2005) described a case where therapy with trastuzumab and vinorelbine was started after week 27 because of metastatic breast...
Oxytocin may be used obstetrically for the induction or augmentation of labor. Clinically important vasopressin deficiency (diabetes insipidus) justifies the use of vasopressin or desmopressin during pregnancy. Careful control of circulatory and kidney function is essential. Von Willebrand's disease type I and platelet dysfunction can also be indications for the administration of desmopressin. The use of the other vasopressin analogs is not grounds for a termination of pregnancy or for Invasive diagnostic procedures.
Revaccination is sometimes necessary because only 5070 of immunocompromised persons, especially dialysis patients, develop antibodies, and the anti-HBs titers in these cases are low. In revaccinated non-responders to primary hepatitis immunization using either 20 mg of plasma-derived vaccine or 10 mg of recombinant vaccine, depending on the vaccine used for previous doses, the revaccinations were well tolerated (81,82). Only 6.6 of the vaccinees reported slight irritation at the injection site, tenderness, minimal pain, or swelling lasting for a few hours up to 2 days.
Barone et al. reported two cases where renal transplant recipients started self-medication with St. John's wort. Both patients experienced sub-therapeutic concentrations of cyclosporine, and one patient developed acute graft rejection due to low cyclosporine concentration. Upon termination of use of St. John's wort, both patients' cyclosporine concentrations returned to therapeutic levels (28). Interaction between St. John's wort and cyclosporine is well documented in the literature (29). Bauer et al. concluded that St John's wort caused rapid and significant reduction in plasma cyclosporine concentrations. Additionally, substantial alteration in cyclosporine metabolite kinetics was also observed (30). Alschner and Klotz reported a case study where a 57-year-old kidney transplant recipient with a long-term regular intake of cyclosporine (125-150 mg day) and prednisolone (5mg day) and routinely monitored cyclosporine trough level (100-130 ng mL) over the past 2 years showed a sudden...
The thiazolidinediones are contraindicated in patients with a hypersensitivity to the drug or any component of the drug and severe heart failure. These drugs are Pregnancy Category C drugs and should not be used during pregnancy unless the potential benefit of therapy outweighs the potential risk to the fetus. The thiazolidinediones are used cautiously in patients with edema, cardiovascular disease, and liver or kidney disease. These drugs may alter the effects of oral contraceptives.
Group II (mGluR2 3) and group III (mGluR4 6 7 8 mGluR4 7 8 have two splice variants) receptors differ in their sequence homology but are both coupled to a different effector system, i.e. they decrease the activity of adenylate cyclase. Both group II and III mGluRs are located largely on presynaptic neurons and glia and modulate the release of glutamate as well as other, e.g. inhibitory, transmitters such as GABA (Salt et al. 1999). The activation of group II and III mGluRs evokes predominantly inhibitory effects on neuronal excitability. However, 4-aminopyrrolidine-2,4-dicarboxylic acid (APDC), a selective and potent group II mGluR agonist, reversibly increased NMDA receptor currents in acutely dissociated PFC pyramidal neurons. Selective group II mGluR antagonists, but not group I mGluR antagonists, blocked APDC-induced enhancement of NMDA receptor currents, suggesting the mediation by mGluR2 3 receptors. Inhibiting PKC or dialysis with Ca2+ chela-tors largely blocked the mGluR2 3...
Three diabetic patients on chronic ambulatory peritoneal dialysis (CAPD) had symptoms of hypoglycemia when glucose readings on strips were higher than 4 mmol l (223). Venous testing showed glucose concentrations as low as 1.8 mmol l. Large amounts of glucose are used in CAPD, which not only affects the regulation of diabetes but can also affect the peritoneal wall. Since 1999, icodex-trin has been used in dialysis fluids. Icodextrin is glucose-free and reduces the need for insulin. However, it is also absorbed systematically and can be metabolized to maltose and maltotriose. Paper systems that use either glucose oxidase or glucose dehydrogenase overestimate glucose readings when icodextrin is used, and patients and their carers are not able to measure low blood glucose concentrations. Another factor is that during end-stage renal insufficiency, insulin catabolism is reduced. This contributes to the problems when CAPD is changed to automated (overnight) peritoneal dialysis, in which...
Elements are the basis of all things. However, human exposure to significant amounts of some elements can lead to adverse health effects including death. Laboratory testing can help identify unrecognized exposures as well as monitor-associated decontamination efforts. Regular testing is also important to identify exposures in populations that are at high risk for exposure to a specific toxic element. For example, aluminum is important to monitor in dialysis patients. Lead is important to monitor in children that live in areas in which environmental lead contamination is prevalent. Mercury is important to monitor in dental workers and individuals for whom predatory fish frequents the diet. Arsenic and cadmium are important to monitor in certain industrial settings. Iron is important to monitor for individuals at risk for iron overload. The quality of laboratory results depends on collection of the appropriate specimen and efforts to minimize external contamination of the specimen with...
Isoniazid can cause neuropsychiatric syndromes, including euphoria, transient impairment of memory, separation of ideas and reality, loss of self-control, psychoses (9), and obsessive-compulsive neurosis (12). Isoniazid should be used with caution in patients with pre-existing psychoses, as it can cause relapse of paranoid schizophrenia (13). Patients on chronic dialysis appear to be vulnerable to neurological adverse drug reactions, because of abnormal metabolism of uremic toxins. It is therefore recommended that a higher than usual dose of pyridoxine be given to patients on dialysis taking isoniazid (14,15).
Whole blood is the specimen of choice for lead and cadmium detection due to the high proportion ( 90 ) of these elements that binds to cellular proteins and localize to erythrocytes. Serum or plasma is the specimen of choice for detecting aluminum toxicity in dialysis patients and to detect iron overload. Sources of external contamination associated with whole blood collection include the blood collection tube and the skin, particularly with collection of capillary specimens. In fact, the vast majority of capillary blood specimens that generate elevated lead results do not confirm as elevated when a second specimen collected with non-trace element-free tubes (venous blood) is tested. Stainless steel needles used to perform venipuncture have not been shown to contribute to falsely elevated toxic element concentrations, but there have been some reports of elemental contamination from evacuated blood collection tubes. Such contamination could arise from the material used to construct the...
Diarrhea is the most frequent manifestation of gastrointestinal infection. Diarrhea is common in both the developed and developing world. Poor water quality and sewage disposal are the main factors for intestinal infections in the developing world, whereas the widespread use of broad-spectrum antibiotics and impaired host community owing to greater numbers of immunocompromised individuals are factors in the developed world. Symptoms of enteric infections are not limited to the gastrointestinal system, the respiratory system, nervous system eyes and skin may also be affected by microorganisms multiplying within the GI tract. For example infection by E. coli can result in kidney damage even so called simple GI infections can result in severe vomiting and diarrhea which in turn can lead to dehydration. Other examples of gastrointestinal infections include esophagitis from candidiasis gastritis from anisakiasis intestinal obstruction from tuberculosis, and proctitis from Chlamydia...
Since p-lactam antibiotics are considered least toxic among all antibacterial agents, their fatal doses are not clear. However, the presence of high blood levels of these antibiotics can cause seizures, nephritis, leukopenia and bleeding disorders 21 . It is well-known that p-lactam antibiotics occasionally cause allergy reactions. The anaphylactic shock caused by parenteral administration is not so rare. The sensitivity test is, therefore, essential before parenteral administration of p-lactam antibiotics. When such a test is neglected or overlooked, resulting fatality due to anaphylactic shock, such a case is regarded as malpractice.
PDGF-B-chain and P-receptor deficient mice show highly similar pheno-types, with abnormal placenta, anemia, thrombocytopenia, impaired kidney development, defective blood vessel maturation, edema, and perinatal death owing to rupture of microvascular aneurysms (5,6). The high phenotypic similarity of PDGF-B-chain and P-receptor knockout animals implies that PDGF-BB is the major ligand for the PDGF-P-receptor during development. The impaired kidney development in B-chain and P-receptor deleted embryos stems from the absence of mesangial cells in the kidney glomerulus. Loss of mesangial cells and replacement of capillary tufts by a few dilated capillary loops resulted in decreased renal filtration in knockout animals (6,22).
Plasma proteins are contraindicated in those with a history of allergic reactions to albumin, severe anemia, or cardiac failure in the presence of normal or increased intravascular volume and in patients on car-diopulmonary bypass. Plasma protein fractions are used cautiously in patients who are in shock or dehydrated and in those with congestive cardiac failure or hepatic or renal failure. These solutions are Pregnancy Category C drugs and are used cautiously during pregnancy and lactation.
In 149 patients undergoing chronic peritoneal dialysis, S. aureus was isolated from 26 patients, 25 from the nares, axillae, or groins and one from the catheter exit site (4). So-called high-level'' mupirocin-resistant organisms (minimum inhibitory concentration 256 mg ml or more) were isolated from four patients. Methicillin-resistant organisms (MRSA) were not detected. One patient with high-level mupirocin-resistant organisms had peritonitis due to S. aureus, resulting in treatment failure and catheter loss. Of 36 patients undergoing continuous ambulatory peritoneal dialysis (mean age 55 years 21 men), who had been applying mupirocin to the catheter exit site once weekly for an average of 3.1 years before the start of the study, three were nasal carriers of S. aureus, and there was only one mupirocin-resistant organism (5). Once-weekly application of mupirocin at catheter exit sites led to comparable rates of colonization by mupirocin-resistant S. aureus as did thrice-weekly or more...
In most individuals, the systolic pressure increases sharply with age, whereas the diastolic pressure increases until about age 55 years and then declines. Older individuals with an elevated systolic pressure have a condition known as isolated systolic hypertension (ISH). When the systolic pressure is high, blood vessels become less flexible and stiffen, leading to cardiovascular disease and kidney damage. Research indicates that treating ISH saves lives and reduces illness. The treatment is the same for ISH as for other forms of hypertension.
Penetration of the BBB is essential for effective pharmacotherapy of CNS disorders. Various techniques have been used to study the pharmacokinetics and pharmacodynamics of CNS active agents by determining unbound drug concentrations in the extracellular fluid of the brain. In vivo techniques include the brain uptake index (27), the brain efflux index (BEI) (28), brain perfusion (29), the unit impulse response method (30) and micro-dialysis (31).
Phenazone nephrotoxicity is well-established, but information is limited. Experimental papillary necrosis can easily be provoked analgesic nephropathy is probably a real danger with antipyrine, especially when it is combined with a stronger inhibitor of prostaglandin synthesis. The effect is probably toxic, since inhibition of prostaglandins is not a marked characteristic of phenazone. Two reports have suggested a causal link between phenazone and renal carcinoma, as is well-known for phenacetin (3,4), but this has not been confirmed.
Calcitriol, used for suppression of parathormone in patients with end-stage renal disease, especially in conjunction with calcium-containing phosphate binders, greatly increases the risks of hypercalcemia and hyperphos-phatemia. Efforts have therefore been made to develop therapies that do not cause an increased calcium burden. Paricalcitol has recently been introduced as an alternative to calcitriol. The efficacy of intravenous paricalcitol and cal-citriol and the risks of hypercalcemia and hyperphosphatemia have been studied in an international, randomized, double-blind comparison in 38 patients in dialysis units (36C). The end points were a reduction of at least 50 in baseline parathormone concentration and the occurrence of hypercalcemia and hyperphos-phatemia. Paricalcitol therapy was started at a dose of 0.04 micrograms kg and increased in 0.04 microgram kg increments every 4 weeks to a maximum allowable dose of 0.24 micro-grams kg or until there was at least a 50 fall in serum...
The bile acid sequestrants are contraindicated in patients with known hypersensitivity to the drugs. Bile acid sequestrants are also contraindicated in those with complete biliary obstruction. These drugs are used cautiously in patients with a history of liver or kidney disease. Bile acid sequestrants are used cautiously during pregnancy (Pregnancy Category C) and lactation (decreased absorption of vitamins may affect the infant).
The antihyperlipidemic drugs, particularly the HMG-CoA reductase inhibitors, have been associated with skeletal muscle effects leading to rhab-domyolysis. Rhabdomyolysis is a very rare condition in which muscle damage results in the release of muscle cell contents into the bloodstream. Rhabdomyolysis may precipitate renal dysfunction or acute renal failure. The nurse is alert for unexplained muscle pain, muscle tenderness, or weakness, especially if they are accompanied by malaise or fever. These symptoms should be reported to the primary health care provider because the drug may be discontinued.
The thiazide diuretics are used cautiously in patients with liver or kidney disease, lupus erythe-matosus (may exacerbate or activate the disease), or diabetes. Additive hypotensive effects occur when the thiazides are given with alcohol, other antihypertensive drugs, or nitrates.
Drug overdose Acute renal insufficiency necessitating hemodialysis occurred in patient who deliberately took potassium iodide solution 50 ml and a small dose of mefenamic acid (6 capsules) as part of a suicide attempt (17A). Iodinated radiographic contrast media can also cause acute renal insufficiency, perhaps as a result of reduced renal blood flow, an intrarenal osmotic effect, or direct tubular toxicity. In this case the authors postulated that iodide toxicity had resulted in hemolysis and hemoglobinuria, which, together with acute interstitial nephritis secondary to inhibition of prostaglandin synthesis from mefenamic acid ingestion, had resulted in acute renal insufficiency. The patient recovered normal renal function after 10 days of hemodialysis. The mechanism of hemolysis resulting from toxic doses of iodine is not clear, although it may reflect inhibition of various red cell enzymes. 17. Sinniah R, Lye WC. Acute renal failure from hemoglobinuric and interstitial nephritis...
Other species of amanita are among the deadliest fungi known. Polypeptide-like toxins in Amanita phalloides, or death cup, can prove fatal or at the very least can cause permanent liver and kidney damage. These mushrooms are common in the temperate climates of Europe and North America. They are responsible for the majority of what is called slow mushroom poisoning in the U.S. In fact, it was only a few years ago that the local newspaper reported a case of amanita poisoning within SLO county. Mushroom poisoning is known as mycetism. In addition the amanita also contain bufotenine which has CNS effects. See the ASIDE which discusses the peptide poisons.
Mary Jo is a thirty-six-year-old white female who received a kidney transplant in April 2005. She was prescribed the usual array of medications to keep her body from rejecting the transplanted organ, including Cyclosporin A, and was considered stable for a period of several months. Indeed, Mary Jo was doing extremely well and was regarded as a model patient for diligence in cooperating with the anti-rejection regimen. In November 2005, however, her blood level of Cyclosporin A dropped precipitously, well below that needed to maintain the transplant effectively. She was admitted to the hospital for a variety of lab tests and a kidney biopsy. Mary Jo required a second kidney transplant in December 2005. Unknown to Mary Jo, St. John's wort interferes with cyclosporine, and by undercutting her anti-rejection drug regimen, she probably caused the need for another transplant. Who or what was at fault for this unfortunate turn of events expensive medical procedure was required to save her...
Microdialysis technique coupled with electrochemical detection (ED) is a relatively new method that allows detection of neurotransmitters and other substances from brain and other tissues. It is based on the insertion of a dialysis probe in a specific area and perfusing it with artificial cerebrospinal fluid (CSF), which, passing in a chamber delimited by the dialysis fiber, becomes enriched with small molecular weight substances diffusing into the fiber because of their concentration gradient. Substances recovered can be assayed by highperformance liquid chromatography (HPLC) to evaluate their concentration in the dialysate, that is closely related to their extracellular concentration in the area investigated. After recovery from surgery, therefore, the effects of drugs or other treatments on the assayed substance can be evaluated in freely moving animals (1).
In an HIV-1-positive kidney transplant recipient, saqui-navir increased the trough concentration of ciclosporin three-fold, resulting in fatigue, headache, and gastrointestinal discomfort. Ciclosporin, like saquinavir, is metabolized by CYP3A. Saquinavir plasma concentrations were likewise increased by ciclosporin. All the symptoms disappeared after downward adjustment of the doses of both ciclosporin and saquinavir (16).
The basic equipment required to start a microdialysis laboratory equipped with ED includes a stock of dialysis fibers that can be obtained from a hospital supplier of artificial kidneys at modest cost and may last for 1-2 yr. To implant probes in the brain it is essential to purchase a stereotaxic apparatus, that although expensive (about 5000), if well kept, lasts for many years. A perfusion pump is necessary to complete the essential microdialysis equipment those in the market range 2000-5000 but are precise and durable. To analyze samples a basic HPLC system is necessary. It includes a pump, a column, detectors with appropriate electrodes, and a handling data system that can cost up to 15,000-20,000 (see Note 11).
Concentric dialysis probes can be prepared with a 7-mm piece of AN 69 (sodium methallyl sulfate copolymer) dialysis fiber (310 pm outer diameter o.d. and 220 pm inner diameter i.d. Hospal, Dasco, Italy), sealed at one end with a drop of epoxy glue. The sealed end is gently sharpened with a thin grain abrasive disk to reduce tissue damage during implant. Two 4-cm long pieces of fused silica (Composite Metal Services, UK) tubing are introduced in the dialysis fiber, taking care to have the inlet reach the lower end and the outlet reach the higher end of the dialyzing portion (1.0 mm) of the fiber. The inlet and the outlet are then sealed to the fiber and to a 18-mm piece of stainless steel (obtained from a 24-gauge needle) that were then inserted into a piece of 200-pL micropipet tip 6 mm long and glued to it. The fiber is finally covered with a thin layer of epoxy glue except for the dialyzing part. The probe is left to dry for 24 h (1,5). Among the wide spectrum of dialysis probes...
Typical adverse effects include hypokalemia, renal impairment (which results from dehydration and pre-renal failure and direct toxic effects on the kidneys), and ototoxicity (usually deafness with frusemide). Mannitol is given by IV for the treatment of oliguria in incipient renal failure in order to lower intracranial pressure. It is also used in glaucoma.
In 81 patients intravenous suramin (peak plasma concentration 300 mg ml trough concentration 175 mg ml) combined with aminoglutethimide 250 mg qds in patients with progressive androgen-refractory prostate cancer after antiandrogen treatment had been withdrawn, effectiveness was limited, whereas most adverse effects were attributed to suramin (3). There were 38 episodes of grade 3 and 4 toxic effects in 29 patients. Severe thrombocyto-penia occurred in four patients. There were four episodes of atrial fibrillation. One patient developed uremia which required dialysis. One patient developed grade 3 neuro-sensory changes, but none had neuromotor changes. There was one episode of grade 4 rash, which was probably attributable to aminoglutethimide, consisting of diffuse erythematous exfoliating papules over the chest, back, arms, and face. All adverse effects were reversible.
The safety and efficacy of terbinafine 250 mg day and itraconazole 200 mg day given for 12 weeks for toenail onychomycosis have been compared in a randomized, double-blind study in 372 patients (19). Adverse events were reported in 39 of the terbinafine-treated patients and in 35 of the itraconazole-treated patients. The mean values of biochemical parameters of liver and kidney function did not change significantly. Terbinafine produced higher rates of clinical cure (76 versus 58 ) and mycological cure (73 versus 46 ) than itraconazole.
Based on a study of 10 patients with automated peritoneal dialysis, it was recommended that for empirical treatment of dialysis-related peritonitis, the dosage of intermittent intraperitoneal tobramycin must be 1.5 mg kg for one exchange during the first day and then 0.5 mg kg thereafter, to reduce the risk of adverse effects (47).
The serotonin syndrome usually occurs within two hours after dosing, and symptoms may subside within 6-24 hours. The combination of MAO inhibitors with SSRIs is potentially lethal. Initial symptoms include nausea and vomiting, tremor, elevated temperature, cardiac arrhythmia, renal failure, and coma, eventually leading to death. In general, ayahuasca should not be used by any individual who is already
Central venous catheters are reluctantly used as blood access for hemodialysis because of safety concerns and frequent complications, e.g. sepsis, thrombosis, and vessel stenosis. Nevertheless, 20 or more of all patients rely on atrial catheters for chronic dialysis because of lack of other access. Potentially fatal risks related to central venous catheters include air embolism (59c), severe blood loss (60c), and electric shock (61c). These specific risks have been substantially eliminated by the inherent design and implantation of Dialock (Biolink Corporation, USA). Dialock is a subcutaneous device consisting of a titanium housing with two passages with integrated valves connected to two silicone catheters. The system is implanted subcutaneously below the clavicle. The tips of the catheters are placed in the right atrium. The port is accessed percutaneously with needle cannulas. 60. Lau G. Iatrogenically-related, fatal haemorrhage occurring in end-stage renal failure a series of...
The primary route of metabolism of DACA is oxidation at C-9 by aldehyde oxidase to give the acridone 87, although oxidative demethylation of the side chain dime-thylamino group has also been observed 73 . Comparative studies of the conversion of DACA to 87 were carried out using aldehyde oxidase preparations from human, guinea pig, and rat. The human enzyme had intrinsic clearance values (Vmax
Acetophenetidin Phenacetin, white crystalline compound, an aniline derivative that is used as a mild analgesic. This drug, which has antipyretic (fever-reducing) as well as analgesic (pain-reducing) effects, may be used alone or in combination with aspirin and either caffeine or codeine such combinations are called APC mixtures. Because of the possible kidney damage that may be caused by high doses and prolonged use of acetophenetidin, aspirin is sometimes used as a substitute. Acetorfina Acetorphine. Acetorphin Acetorphine. Acetorphine C27H35NO5. Derivate of the-baine under international control according to the UN Single Convention 1961 and its amendments, Schedule I and IV. Molecular weight 453. 6. Percentage of anhydrous base 100.
Today, at least in Europe, an increasing number of patients are provided with health care services at home (Hutchinson and Graham, 1998). Such services include supply of home parenteral nutrition (HPN), home dialysis, i.v., antibiotic therapy at home, and patient-controlled analgesia (PCA) (Hutchinson and Graham, 1998 Hutchinson 1998). Standard bags of TPN are prepared in certain hospital pharmacies, sealed into a dark-colored outer plastic bag, and stored in a refrigerator for several weeks (Hutchinson, 1998). Information on correct storage and administration of TPN preparations at home should be provided by the pharmacist and health care personnel involved, with a focus also on the protective effect of the outer colored bag.
The corticosteroids arc grouped according to their capacity for Na+ retention, their effects on carbohydrate metabolism, and their anti-inflammatory effects. Thus, glucocorticoids have pleoiotropic effects and arc used in clinical practice in (as well as replacement therapy in cases of adrenal insufficiency) treating diverse diseases such as inflammatory rheumatic disorders, asthma, autoimmune diseases (systemic lupus erythematosus and others), acute kidney transplant rejection, and allergic and skin diseases. In pregnant women at risk for preterm birth, corticosteroids are also used for the induction of lung maturity. High doses of daily glucocorticoids are usually required in patients with severe diseases involving major organs, whereas alternate-day regimens may be used in patients with less aggressive disease. Intravenous glucocorticoids (pulse therapy) are frequently used to initiate therapy in patients with rapidly progressive, inmunologically mediated diseases (Rournpas 1993).
Fidarestat is an aldose reductase inhibitor of the same class as sorbinil, which was withdrawn because of hypersensitivity reactions in more than 10 of patients. In 279 patients in a multicenter, double-blind, placebo-controlled study for 1 year nerve conduction and subjective symptoms improved 99C . There were no skin rashes or changes in liver enzymes or kidney function. 2. Mehmet S, Quan G, Thomas S, Goldsmith D. Important causes of hypoglycaemia in patients with peritoneal dialysis. Diabetes Med 2001 18 679-82.
In humans adverse reactions to contrast media vary greatly in type and severity from slight nausea or mild hot flush through a broad spectrum of increasingly severe cutaneous, respiratory, neurological, and cardiovascular disturbances that may, in extreme cases, result in the sudden death of the patient (454457,459,465,469, 507).Ansari and Baldwin (523) reported acute renal failure after urography with meglumine diatrizoate, angiography with meglumine and sodium diatrizoate, oral cholecystography with iopanoic acid, and cholangiography with iodipamide. Roylance et al. (524, 525) reported the incidence of reactions to urographic agents. Lasser et al. (543) compared the patient reactions to ionic and nonionic contrast media based on data on reactions to X-ray contrast materials collected under the supervision of the FDA Division of Epidemiology and Surveillance and manufacturer data from 1990 through 1994. In 1992-1994 there were more than 16 million examinations performed in toto each...
Despite early reports of transferrin mediated iron uptake (Haldar et al. 1986 Rodriguez and Jungery 1986), the bulk of experimental evidence excludes a requirement by parasites for extracellular iron. An important physiological study showed Plasmodium culture medium, which was depleted of transferrin by 500-1000-fold, supported Plasmodium growth well, while inhibiting fibroblasts dependent on transferrin uptake (Sanchez-Lopez and Haldar 1992). Free iron in Plasmodium culture medium has been determined to range from 1 to 10 M. Dialysis removal of free iron to below 1 M had no effect on parasite growth (Peto and Thompson 1986). Extracellular impermeable dextran-DFO also did not inhibit growth in culture (Scott et al. 1990). Intracellular low molecular weight proteins bind iron, but when DFO conjugates were loaded into resealed erythrocyte ghosts replication was not inhibited (Loyevsky et al. 1993 Scott et al. 1990). Egan has measured equal
Alcoholic pancreatitis A disorder characterised by inflammation and necrosis of the pancreas, often accompanied by fibrosis and malfunction, related to the consumption of hazardous levels of alcohol. Alcoholic pancreatitis may be acute or chronic. The acute form presents with upper abdominal pain, anorexia, and vomiting, and can be complicated by hypotension, renal failure, lung disease, and psychosis. The chronic form usually presents with recurrent or persistent abdominal pain, anorexia, and weight loss there may be signs of pancreatic deficiency involving the exocrine functions of the pancreas (e.g. malabsorption, nutritional deficiency) or the endocrine functions (diabetes mellitus). Alcoholic pancreatitis has ICD-10 diagnos K86.0.
Headache, 21.95 headaches in children, 23.114 nephropathy, 21.98 Androgens, in women, 24.477 Anesthesia, dental, safety of, 16.122 Anesthetics liver damage, 17.98, 18.94 overdose, 23.117 Penicillins, acute desensitization, 23.252 Peritoneal dialysis fluids, effects on peritoneum, 22.381 peritoneum, peritoneal dialysis, 22.381 pleurodesis, 25.189 Musculoskeletal
Somogyi AA, Shanks CA, Triggs EJ. The effect of renal failure on the disposition and neuromuscular blocking action of pancuronium bromide. Eur J Clin Pharmacol 1977 12(1) 23-9. 29. Bevan DR, Archer D, Donati F, Ferguson A, Higgs BD. Antagonism of pancuronium in renal failure no recurariza-tion. Br J Anaesth 1982 54(1) 63-8. 30. Gramstad L. Atracurium, vecuronium and pancuronium in end-stage renal failure. Dose-response properties and interactions with azathioprine. Br J Anaesth 1987 59(8) 995-1003.
Disorder of skeletal muscle related to the use of alcohol or other drugs. The disorder can be acute (when it is termed acute rhabdomyoly-sis), with extensive necrosis of muscles, which are tender and swollen, and may be complicated by myoglobinuria and renal failure. The chronic form presents with insidious weakness and wasting of the proximal muscles. G72. 0, G72. 1
Rodents show spontaneous alternation behaviour when tested in simple T- or Y-shaped mazes. They can also be forced to alternate, i.e. when food reward is placed at the end of the goal arm of the T Y. As pointed out for the eight-arm radial maze, this paradigm uses food or drinking of juice as reward and is contra-indicated when using cannabinoids. Systemic administration of A9THC prior to daily testing decreased the alternation score (Nava et al. 2000). In control animals, in vivo brain dialysis confirmed an alternation-induced release of acetylcholine in hippocampus, which was smaller in the A9THC group. In addition, the alternation impairment and the acetylcholine release depression persisted in animals treated with A9THC twice daily with 5 mg kg A9THC i.p. for up to 1 week (Nava et al. 2001). Both effects were fully reversed by rimonabant, suggesting that no tolerance developed after chronic 5-dayA9THC exposure.
The complex of azathioprine-associated multisystemic adverse effects is referred to by the misnomer azathioprine hypersensitivity syndrome.'' This well-characterized reaction has been described in numerous case reports and includes various symptoms which can occur separately or concomitantly they comprise fever and rigors, arthralgia, myalgia, leukocytosis, cutaneous reactions, gastrointestinal disturbances, hypotension, liver injury, pancreatitis, interstitial nephritis, pneumonitis, and pulmonary hemorrhage (SED-13, 1121) (SEDA-20, 341) (SEDA-21, 381) (SEDA-22, 410) (7). Isolated fever and rigors are sometimes observed, and severe renal and cardiac toxicity or leukocytoclastic cutaneous vasculitis are infrequent. Symptoms usually occur within the first 6 weeks of treatment and can mimic sepsis. The initial febrile reaction is often misdiagnosed as infectious, and could be associated with acute exacerbation of the underlying disease, for example myasthenia gravis (SEDA-21, 381)...
The use of traditional plant remedies has been implicated in 35 of all cases of acute renal failure in Africa 59-63 . Precise identities of the culprit substances are mainly unknown, as well as the toxicological characteristics and pathogenetic mechanisms involved. Most data published are case reports, with no clear identification of the herbal product involved in the renal toxic effect. Various renal syndromes have been reported after the use of medicinal plants. They include acute tubular necrosis, acute interstitial nephritis, Fanconi's syndrome, hypokalemia, hypertension, papillary necrosis, chronic interstitial nephritis, nephrolithiasis, urinary retention, and cancer of the urinary tract. Conversely, herbal medicine also may be hazardous for renal patients because it may interact with such drugs as cy-closporine or carry significant amounts of potassium.
Cidofovir is being used in the transplant field for prophylaxis and treatment of CMV infections, because of its dosing convenience. Renal toxicity, including severe toxicity requiring dialysis, has been noted (2c). The risk of renal toxicity was higher in patients with established CMV infections than in those who
Equilibrium dialysis technique was used by several investigators to estimate free lidocaine concentration. Routledge et al. subjected two 1 ml aliquots of plasma to equilibrium dialysis using a Teflon equilibrium dialysis cell. The dialysis was performed against Sorenson's phosphate buffer (containing 0.5 w v sodium chloride), and the pH was adjusted to 7.4 to which lidocaine hydrochloride was added (3 g mL buffer). This concentration was achieved by adding unlabeled lidocaine hydrochloride (2.8 g mL) to radioactive 14C lidocaine (200ng mL). The buffer and plasma compartment were separated by a Spectrapor dialysis membrane with a molecular weight cut-off range of 12,000-14,000, and the cells were rotated in a water bath for 3h at 37 C. The authors demonstrated that equilibrium was achieved in 3h and the binding was similar in heparinized plasma, citrated plasma, and serum. After dialysis, 300 l of aliquots were withdrawn from each side of the cells, scintillation fluid was added, and...
Urinary tract The epidemiology of the nephrotoxicity of conventional amphotericin B has been investigated in a retrospective study in 494 adult in-patients who received two or more doses (1c). Nephrotoxicity was defined as a 50-100 increase in the baseline crea-tinine concentration. The median cumulative dose was 240 mg and most of the patients received it for empirical therapy. Overall, 139 patients (28 ) had renal toxicity, including 58 (12 ) with moderate to severe nephrotoxicity. For each 10 mg increase in the mean daily dose, the adjusted rate of renal toxicity increased by a factor of 1.13. Five risk factors were defined a mean daily dose of 35 mg or more, male sex, weight 90 kg or more, chronic renal disease, and concurrent use of amikacin or ciclosporin. The incidence of moderate to severe nephrotoxicity was 4 in patients with none of these risk factors, 8 in those with one, 18 in those with two, and 29 in those with three or more. Nephrotoxicity rarely led
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