Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0030193 (pain)
 261,466 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Fabry disease is an X-linked lysosomal storage disease caused by deficiency of the enzyme alpha-galactosidase A and results in pain, progressive renal impairment, cardiomyopathy, and cerebrovascular disease. The results of two major randomized, double-blind, placebo-controlled clinical trials and open-label extensions have shown that replacement of the deficient enzyme with either of two preparations of recombinant human alpha-galactosidase A, agalsidase-alfa, and agalsidase-beta is safe. Biweekly i.v. infusions of 0.2 mg/kg of agalsidase-alfa were associated with a significant decrease in pain and stabilization of renal function. Biweekly infusions of 1 mg/kg of agalsidase-beta were associated with virtually complete clearing of accumulated glycolipid substrate from renal and cutaneous capillary endothelial cells. Several smaller, open-label studies, along with observations made in the course of monitoring large numbers of patients on enzyme replacement therapy, indicated that treatment stabilizes renal function and produces significant improvements in myocardial mass and function. Treatment of Fabry disease by enzyme replacement has a significant impact on at least some serious complications of the disease.
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PMID:Enzyme replacement therapy of Fabry disease. 1607 82

Congenital insensitivity to pain with anhidrosis (CIPA) is an autosomal recessive disorder caused by mutations in the neurotrophic tyrosine receptor kinase 1 (NTRK1) gene which encodes the receptor for nerve growth factor (NGF). We report the clinical course in three sibs with CIPA and proven NTRK1 gene mutations with a follow-up over a 25-year period in one of them. They had the characteristic clinical features of an abnormally high pain threshold, and mental retardation; in addition their clinical course was marked by the occurrence of early onset renal disease with recurrent microhematuria and proteinuria and frequent observations of increased serum creatinine and blood urea levels. Light microscopy study of a renal biopsy performed in one of them at age of 20 months showed focal glomerulosclerosis, interstitial fibrosis and tubular atrophy. This patient and his younger brother died because of renal failure at the age of 25 years and 14 years, respectively. The sister still alive showed renal impairment and deep venous thrombosis associated with lupus anticoagulant activity, decrease of circulating autoreactive CD5 (+) B lymphocytes and increased urinary levels of IgG and kappa and lambda light chains, suggesting a possible defect in regulation of B-lymphocyte function. In the light of the NGF-related molecular defect, the extraneurological tissue involvement in CIPA might in part reflect dysregulation of immune mechanisms which possibly brings about a chronic inflammatory response. This, in turn, could result in renal disease which should be mentioned among the life-threatening complications associated with this disorder.
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PMID:Congenital insensitivity to pain with Anhidrosis (NTRK1 mutation) and early onset renal disease: clinical report on three sibs with a 25-year follow-up in one of them. 1613 53

Lumiracoxib (Prexige) is a selective cyclo-oxygenase (COX)-2 inhibitor developed for the treatment of osteoarthritis, rheumatoid arthritis and acute pain. Lumiracoxib possesses a carboxylic acid group that makes it weakly acidic (acid dissociation constant [pKa] 4.7), distinguishing it from other selective COX-2 inhibitors. Lumiracoxib has good oral bioavailability (74%). It is rapidly absorbed, reaching maximum plasma concentrations 2 hours after dosing, and is highly plasma protein bound. Lumiracoxib has a short elimination half-life from plasma (mean 4 hours) and demonstrates dose-proportional plasma pharmacokinetics with no accumulation during multiple dosing. In patients with rheumatoid arthritis, peak lumiracoxib synovial fluid concentrations occur 3-4 hours later than in plasma and exceed plasma concentrations from 5 hours after dosing to the end of the 24-hour dosing interval. These data suggest that lumiracoxib may be associated with reduced systemic exposure, while still reaching sites where COX-2 inhibition is required for pain relief. Lumiracoxib is metabolised extensively prior to excretion, with only a small amount excreted unchanged in urine or faeces. Lumiracoxib and its metabolites are excreted via renal and faecal routes in approximately equal amounts. The major metabolic pathways identified involve oxidation of the 5-methyl group of lumiracoxib and/or hydroxylation of its dihaloaromatic ring. Major metabolites of lumiracoxib in plasma are the 5-carboxy, 4'-hydroxy and 4'-hydroxy-5-carboxy derivatives, of which only the 4'-hydroxy derivative is active and COX-2 selective. In vitro, the major oxidative pathways are catalysed primarily by cytochrome P450 (CYP) 2C9 with very minor contribution from CYP1A2 and CYP2C19. However, in patients genotyped as poor CYP2C9 metabolisers, exposure to lumiracoxib (area under the plasma concentration-time curve) is not significantly increased compared with control subjects, indicating no requirement for adjustment of lumiracoxib dose in these subjects. Lumiracoxib is selective for COX-2 compared with COX-1 in the human whole blood assay with a ratio of 515 : 1 in healthy subjects and in patients with osteoarthritis or rheumatoid arthritis. COX-2 selectivity was confirmed by a lack of inhibition of arachidonic acid and collagen-induced platelet aggregation. COX-2 selectivity of lumiracoxib is associated with a reduced incidence of gastroduodenal erosions compared with naproxen and a lack of effect on both small and large bowel permeability. Lumiracoxib does not exhibit any clinically meaningful interactions with a range of commonly used medications including aspirin (acetylsalicylic acid), fluconazole, an ethinylestradiol- and levonorgestrel-containing oral contraceptive, omeprazole, the antacid Maalox, methotrexate and warfarin (although, as in common practice, routine monitoring of coagulation is recommended when lumiracoxib is co-administered with warfarin). As such, dose adjustments are not required when co-administering these agents with lumiracoxib. In addition, moderate hepatic impairment and mild to moderate renal impairment do not appear to influence lumiracoxib exposure.
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PMID:Clinical pharmacology of lumiracoxib: a selective cyclo-oxygenase-2 inhibitor. 1637 23

Ibandronate is an experimental intravenous bisphosphonate under study for the prevention or treatment of osteoporosis and skeletal complications of bone metastases, as well as hypercalcemia of malignancy. To review the data on this drug, PubMed/MEDLINE was searched for pertinent studies in English; data from January 1986-October 2005 were reviewed. In preclinical studies, ibandronate was an extremely potent bisphosphonate compared with its predecessors and was active in all animal models of human postmenopausal and corticosteroid-associated osteoporosis. Similar to other bisphosphonates, ibandronate exhibits antitumor activity and prevents or reduces bone metastases. Forty to fifty percent of the dose is bound to bone; renal clearance of unchanged drug accounts for 70% of total body clearance. Early clinical trials demonstrated efficacy and tolerability of intravenous ibandronate in the prevention or treatment of postmenopausal and corticosteroid-associated osteoporosis when administered once every 3 months. Intravenous ibandronate also reduces skeletal complications of bone metastases, including pain, although the cumulative dose used is much higher than that used in osteoporosis, as the drug is administered every 3-4 weeks. Single doses of intravenous ibandronate are probably also effective in the treatment of hypercalcemia of malignancy. The major tolerability issue with intravenous bisphosphonates is renal safety, thus the drugs generally require infusion (e.g., 0.25 hr for zoledronic acid, 2-24 hrs for pamidronate). However, intravenous ibandronate can be administered by bolus injection over a few minutes without an elevated risk of nephrotoxicity. The experimental intravenous dosage is 2 mg every 3 months for treatment or prevention of osteoporosis, and 2-6 mg every 3-4 weeks or in a single dose for treatment of bone metastases or hypercalcemia of malignancy, respectively. Ibandronate can be used in the presence of severe renal impairment with proper dosage adjustment. The drug will be an interesting addition to the available drugs for osteoporosis, bone metastases, and hypercalcemia of malignancy. Studies of intravenous ibandronate as an adjunctive treatment for cancers that tend to metastasize to bone are under way. Whether intravenous ibandronate will be a therapeutic advance is best answered by randomized, controlled trials. These are ongoing and should provide data with which to make better-informed choices concerning intravenous bisphosphonates.
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PMID:Ibandronate, an experimental intravenous bisphosphonate for osteoporosis, bone metastases, and hypercalcemia of malignancy. 1663 95

Calciphylaxis, or calcific uremic arteriopathy, is a rare complication of end-stage renal impairment. It is characterized by the development of small vessel vasculopathy with subcutaneous necrosis and ulceration. Intense pain and cutaneous hyperesthesia are prominent features. Mortality rates are high, and the resulting morbidity is significant. While symptomatic management is the mainstay of treatment, it can be challenging. We describe the symptomatic management of a series of three patients with calciphylaxis. Particular emphasis is placed on the use of multimodal analgesia with high-dose opioids, ketamine, and benzodiazepines and on the use of preemptive analgesia.
J Pain Symptom Manage 2006 Aug
PMID:Symptomatic management of calciphylaxis: a case series and review of the literature. 1820 64

In this paper we describe the causes, patterns of presentation, and management of obstructive uropathy in Sudanese patients in a retrospective multi-center audit. All patients who presented with obstructive uropathy during 2005 were included in this study. All of the patients were subjected to serial investigations including imaging and tests of renal function. Diversion, stenting, and/or definitive surgery were performed in order to relieve the obstruction. Five hundred twenty patients were diagnosed with obstructive uropathy during this period; 345 (66%) patients presented with chronic obstruction and 175 (34%) with acute obstruction. Of the study patients, 210 (40%) presented with significant renal impairment; 50 (23%) of them required emergent dialysis. The patterns of clinical presentation of the obstructed patients included pain at the site of obstruction in 48%, lower urinary tract symptoms in 42%, urine retention in 36.5%, mass effect in 22%, and anuria in 4%. Patients in the pediatric age group constituted 4% of the total. The common causative factors of obstruction included congenital urethral valves, pelvi-ureteral junction obstruction, urolithiasis, and iatrogenic trauma, especially in the obstetric practice. Renal function was completely recovered with early management in 100% of patients with acute obstruction and was stabilized in 90% of patients with chronic obstruction. Four patients were diagnosed with end-stage renal failure; two of them were transplanted. The mortality rate in this study was less than 0.3%.
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PMID:Obstructive uropathy in Sudanese patients. 1697 Feb 66

A concept of balanced analgesia using nonsteroidal anti-inflammatory drugs (NSAIDs), paracetamol (acetaminophen), opioids, and corticosteroids can also be used in patients with pre-existing illnesses. NSAIDs are the most effective treatment for acute pain of moderate intensity in children; however, these drugs should be avoided in patients at increased risk for serious side effects, e.g. patients with renal impairment, bleeding tendency, or extreme prematurity. NSAIDs can be given with minimal risks to the younger child with mild to moderate asthma, and, in these patients, the use of steroids can be encouraged; in addition to their antiemetic and analgesic action, a beneficial effect on asthma symptoms can be expected. In the non-intubated child with cerebral trauma, exaggerated sedation caused by opioids and increased bleeding tendency caused by NSAIDs must be avoided. In neonates and small infants, the oral administration of sucrose or glucose is helpful to minimize pain reaction during short uncomfortable interventions.
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PMID:[Systemic analgesia adapted to the children's condition]. 1753 98

Management of pain in the elderly is very challenging. First, the compromised ability to perceive pain because of loss of sensory neurons and other comorbid conditions such as dementia and degenerative joint diseases make the assessment of severity source and localization of pain very difficult. Second, decrease in the renal and hepatic blood flow and decrease in the hepatic and renal mass, along with decrease in volume of distribution caused by decrease in total body water and hypoproteinemia, makes the elderly very sensitive to adverse effects of different pain medicines. Third, many elderly patients have comorbid conditions causing impaired hepatic and renal impairment. In this article, we review the role of 2 more commonly used opiates, morphine and hydromorphone, in elderly patients with hepatic and renal impairment.
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PMID:Use of hydromorphone (Dilaudid) and morphine for patients with hepatic and renal impairment. 1766 20

The number of newly diagnosed cases of multiple myeloma in the Czech Republic is about 3-4 per 100 000 persons per year. In the higher age groups, the incidence increases. Multiple myeloma is an illness that reacts well to treatment which can result in periods of remission lasting for years. Some of the patients are even able to return to work. A pre-requisite for successful treatment is early diagnosis and this is usually in the hands of first line physicians. This is the reason why the Czech Myeloma Group, in conjunction with neurologists, orthopedicians and radio diagnosticians has issued the following recommendations for first line physicians containing a more detailed description of the symptoms and the diagnostic pitfalls of the disease. This disease reminds a chameleon for the variety of its symptoms. For the sake of clarification, we shall divide multiple myeloma symptoms into five points, each of which is reason enough to warrant an examination to confirm or rule out a malignant cause of health problems (a negative result does not automatically mean exclusion). If any of the recommended examinations results positive, the diagnostic process must be continued, in which case a general practitioner refers the patient to a specialist health centre. Observing these recommendations should minimize the number of cases of late diagnosis. 1. Bone destruction symptoms. - Unexplained backache for more than one month in any part of spine even without nerve root irritability or without pain in other part of skeleton (ribs, hips, or long bones). - Pain at the beginning of myeloma disease is very similar to benigne common discopathy, however the intensity of backache is decreasing within one months in benigne disease. In the case of malignant process the intensity of bone pain is steadily increasing. - Immediate imaging and laboratory investigation are indicated by resting and night pain in spinal column or in any part of skeleton. - Backache with the sign of spinal cord or nerve compression should be sent for immediate X Ray, and focussed CT/MRI followed by acute surgery if needed. - Osteoporosis especially in men and premenopausal women. 2. Features of changed immunity or bone marrow function. Persistent and recurrent infection, typical is normochromic anaemia, with leucopenia and trombocytopenia. 3. Raised erythrocyte sedimentation rate even increase concentration of total plasma protein. 4. Impaired renal function. Increased level of creatinin or proteinuria, nephrotic syndrome with bilateral legs oedema. 5. Hypercalcemia with typical clinical symptoms (polyuria with dehydratation, constipation, nausea, low level conscience, coma). Every one from these points has to be reason for general medical doctor to start battery of tests: -X-ray of bones focused to painful area (mandatory before physiotherapy, local anaesthesia or other empiric therapy). If plain X-ray does not elucidate pain and symptoms are lasting more than one month, please consider all circumstances and results from laboratory investigation. This patient needs referral to the centre with MRI/CT facilities (CT or MRI is necessary investigation in case of nerve root or spine compression). -Investigation of erythrocyte sedimantion rate (high level of sedimentation of erythrocyte can indicate multiple myeloma). -Full blood count. -Basic biochemical investigation serum and urine: serum urea, creatinin, ionts including calcium, total protein, and albumin CRP (high concentration of total protein indicates myeloma, low level of albumin indicates general pathological process, similary increased concentration of fibrinogen, impaired renal function indicates myeloma kidney, however hypercalcemia is typical for highly aggressive myeloma). -Quantitative screening for IgG, IgM and IgA in serum (isolated raised level one of immunoglobulin with decreased level of the others indicates myeloma). -Common electrophoresis of serum is able to detect monoclonal immunoglobulin level at few gramm concentration. If all the laboratory investigation are in normal level the possibility that the current problems are multiple myeloma origine is smaller, but it does not exclude one of rare variant--non secretory myeloma (undifferentiated plasmocyt lost characteristic feature to produce monoclonal immunoglobulin). If any of tests indicate the possibility of myeloma, patient require urgent specialist referral to department with possibility to make diagnosis of malignant myeloma.
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PMID:[Recommendations for early identification of damage to the skeleton by malignant processes, and for early diagnosis of multiple myeloma]. 1817 27

This is a case report of an association between morphine administration and occurrence of hydronephrosis with acute renal failure. This premature female infant born at 27 weeks of gestation had moderate hydronephrosis with acute renal impairment while receiving morphine infusion for pain management after chest-tube insertion. All these findings were reversed after stopping morphine and urinary catheterization. Follow-up renal ultrasound and voiding cystourethrogram showed resolution of hydronephrosis with no evidence of vesicoureteral reflux. Morphine is associated with reversible hydronephrosis and renal impairment in premature infants.
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PMID:Renal impairment and hydronephrosis in a premature infant following morphine infusion: case report. 1848 Nov 4


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