Patients uremic

This contains, besides ordinary fats, about 10% of croton-resin, the active component producing the local and systemic effects of the oil. It is destroyed by boiling with alkalis. Croton oil is the most violent of all cathartics, 1/2 to 1 drop producing burning in the mouth and stomach, often vomiting, and after 1/2 to 3 h, several extensive fluid evacuations, with much colic and tenesmus. It was formerly used in extreme cases of constipation, and in unconscious patients (uremic and... 

Phenol and p-cresol noticeably accumulate in the serum of undialyzed and dialyzed uremic patients they play a role in the development of uremic coma and defective platelet aggregation. They are synthesized in the small intestine from phenylalanine and tyrosine through 4-hydroxybenzoic acid and 4-hydroxyphenylacetic acid, respectively, by intestinal bacteria, as shown in Fig. 9. Aerobic bacteria tend to produce phenol from tyrosine, whereas anaerobic bacteria produce p-cresol. These phenols are absorbed from intestine and normally excreted into urine, fri uremia, renal clearance of the phenols is impaired, leading to accumulation of the phenols in the blood. Compared to healthy controls, the serum p-cresol levels are 7-10 times higher in continuous ambulatory peritoneal dialysis patients, uremic outpatients, and hemodialysis patients. 

Urea Pharmacokinetics. Pharmacokinetics summarizes the relationships between solute generation, solute removal, and concentration in a patient s blood stream. In the context of hemodialysis, this analysis is most readily appHed to urea, which has, as a consequence, become a surrogate for other uremic toxins in the quantitation of therapy and in attempts to describe its adequacy. In the simplest case, a patient is assumed to have no residual renal function. Urea is generated from the breakdown of dietary protein, accumulates in a single pool equivalent to the patient s fluid volume, and is removed uniformly from that pool during hemodialysis. A mass balance around the patient yields the following differential equation ... 

Contraindicated in patients who are anuric or uremic or have chronic respiratory acidosis or salicylate toxicity... 

Nonpharmacologic Therapy The incidence and severity of bleeding associated with uremia has decreased since dialysis has become the mainstay of treatment for ESRD. Dialysis initiation improves platelet function and reduces bleeding time.42 Improved care of the patient with ESRD, with anemia treatment and improvement in nutritional status, are also likely contributors to decreased uremic bleeding. 

Pharmacologic Therapy Treatments used to decrease bleeding time in patients with uremic bleeding include cryoprecipitate, which contains various components important in platelet aggregation and clotting, such as von Willebrand factor and fibrinogen. Cryoprecipitate decreases bleeding time within 1 hour in 50% of patients. However, cost and the risk of infection have limited the use of cryoprecipitate. 

EHEC are the pathogenic subgroup of Stx-producing E. coli (STEC). Acute hemorrhagic colitis has been associated mainly with the 0157 H7 serotype. This serotype has been responsible for larger outbreaks of infection, has higher rates of complications, and appears to be more pathogenic than non-EHEC STEC strains. The spectrum of disease associated with E. coli 0157 H7 includes bloody diarrhea, which is seen in as many as 95% of patients, nonbloody diarrhea, hemolytic-uremic syndrome (HUS), and thrombotic thrombocytopenic purpura. 

Uremic and dialysis encephalopathies. Patients with renal failure continue to manifest neuropsychiatric symptoms despite significant advances in therapeutics and management. Patients with renal failure who are not yet on dialysis develop an array of symptoms, including clouding of consciousness, disturbed sleep patterns, tremor and asterixis that may progress to coma and death. 

Uremia results in increased permeability of the blood-brain barrier to sucrose and insulin K+ transport is enhanced whereas Na+ transport is impaired. There is an increase in brain osmolarity in acute renal failure due to the increase in urea concentrations. However, in contrast to acute renal failure, the increase in osmolarity in chronic renal failure results from the presence of idiogenic osmoles in addition to urea. CBF is increased in uremic patients but CMR02 and CMR are decreased. In the brains of rats with acute renal failure, ATP, phosphocreatine and glucose are increased whereas AMP, ADP and lactate are decreased, most probably as a result of decreased energy demands. 

Parathyroid hormone (PTH) produces CNS effects in normal subjects and neuropsychiatric symptoms are frequently encountered in patients with primary hyperparathyroidism, where EEG changes resemble those described in acute renal failure. Circulating PTH is not removed by hemodialysis. In uremic patients both EEG changes and neuropsychiatric symptoms are improved by either parathyroidectomy or medical suppression of PTH. The mechanism whereby PTH causes disturbances of CNS function is not well understood, but it has been suggested that increased PTH might facilitate the entry of Ca2+ into the cell resulting in cell death. 

CKD stage 5, previously referred to as end-stage renal disease (ESRD), occurs when the GFR falls below 15 mL/min per 1.73 m2 body surface area. The patient with stage 5 CKD requiring chronic dialysis or renal transplantation for relief of uremic symptoms is said to have ESRD. 

Continuous renal replacement therapy is used for the management of fluid overload and removal of uremic toxins in patients with acute renal failure and other conditions. Drug therapy individualization for patients receiving continuous renal replacement therapy is discussed in Chap. 75. 

Finally, the successful use of vincristine in the treatment of drug-induced microangiopathic hemolytic anemia, a disease resembling the hemolytic uremic syndrome rarely seen subsequent to administration of mitomycin C or other chemotherapy has been described in two patients with this disorder (79). 

In uremia there are present in the serum a variety of known and unknown metabolites that can produce aberrant laboratory results. Significant differences in glucose concentration have been observed in such specimens analyzed by ferricyanide (F2a) or Fe (II)-5-pyridylbenzo-diazepin-2-one reduction methods compared to glucose oxidase procedures (K7a). In a patient with elevated creatinine (15 mg/100 ml) and uric acid (10 mg/100 ml), the glucose value determined by the automated alkaline ferricyanide procedure was overestimated by 20 mg/100 ml (C4). In uremic patients undergoing chronic hemodialysis there is a decrease in transaminase activity. In 11 of 19 such patients, there was... 

Inhibitors of lactic dehydrogenase have been reported in commercial preparations of NAD+ and NADH (B4, M6, S28). The concentration of inhibitory substances varied from lot to lot. In a serum lactic dehydrogenase study with NAD+ from 8 sources, activities were found to vary from 145 to 75 units (B4). Inhibitors of lactic dehydrogenase activity have also been observed in dialyzates in uremic patients (W8) and in human urine (G8). The purity of available substrate can also effect enzyme activity. Schwartz and Bodansky observed that, in 6 batches of fructose 6-phosphate, all weighed to a 0.5 mM concentration, the actual concentration varied from 0.13 mAf to 0.55 mM (S14). 

Pericardial effusion Pericardial effusion, occasionally with tamponade, has occurred in approximately 3% of treated patients not on dialysis, especially those with inadequate or compromised renal function. Many cases were associated with connective tissue disease, the uremic syndrome, CHF or fluid retention, but were instances in which these potential causes of effusion were not present. Observe patients closely for signs of pericardial disorder. Perform echocardiographic studies if suspicion arises. More vigorous diuretic therapy, dialysis, pericardiocentesis, or surgery may be required. If the effusion persists, consider drug withdrawal. 

Drug/Lab test interactions Thiazides may decrease serum PBI levels without signs of thyroid disturbance. Thiazides also may cause diagnostic interference of serum electrolyte, blood, and urine glucose levels (usually only in patients with a predisposition to glucose intolerance), serum bilirubin levels, and serum uric acid levels. In uremic patients, serum magnesium levels may be increased. Bendroflumethiazide may interfere with the phenolsulfonphthalein test due to decreased excretion. In the phentolamine and tyramine tests, bendroflumethiazide... 

Myopathy and neuropathy Colchicine myoneuropathy appears to be a common cause of weakness in patients on standard therapy who have elevated plasma levels caused by altered renal function. It is often unrecognized and misdiagnosed as polymyositis or uremic neuropathy. Proximal weakness and elevated serum creatine kinase are generally present, and resolve in 3 to 4 weeks following drug withdrawal. Maiabsorption of vitamin B-f2- Colchicine induces reversible malabsorption of vitamin B-12, apparently by altering the function of ileal mucosa. 

Absorption/Distrlbutlon - Phenytoin is slowly absorbed from the small intestine. Rate and extent of absorption varies and is dependent on the product formulation. Bioavailability may differ among products of different manufacturers. Administration IM results in precipitation of phenytoin at the injection site, resulting in slow and erratic absorption, which may continue for up to 5 days or more. Plasma protein binding is 87% to 93% and is lower in uremic patients and neonates. Volume of distribution averages 0.6 L/kg. Phenytoin s therapeutic plasma concentration is 10 to 20 mcg/mL, although many patients achieve complete seizure control at lower serum concentrations. 

Thrombotic thrombocytopenic purpura/hemolytic uremic syndrome (TTP/HUS) TTP/HUS which has resulted in death, has occurred in immunocompromised patients receiving acyclovir therapy. 

Among the adverse events that were reported at a rate of 3% or more and less than 20%, the following were more prominent in patients maintained on sirolimus 5 mg/day vs 2 mg/day Epistaxis, lymphocele, insomnia, thrombotic thrombocytopenic purpura (hemolytic-uremic syndrome), skin ulcer, increased LDH, hypotension, facial edema. 

Bell, W. R., Braine, H. G., Ness, P. M., and Kidder, T. S., Improved survival in toom-botic thrombocytopenic purpura hemolytic-uremic-syndrome-cUnical experience in 108 patients. 

Akpolat T, Gumus T, Bedir A, Adam B. Acute effect of trandolapril on serum erythropoietin in uremic and hypertensive patients. J Nephrol 1998 11 94-7. 

Some disease states (e.g., hyperalbuminemia, hy-poalbuminemia, uremia, hyperbilirubinemia) have been associated with changes in plasma protein binding of drugs. For example, in uremic patients the plasma protein binding of certain acidic drugs (e.g., penicillin, sulfonamides, salicylates, and barbiturates) is reduced. 

Sarnatskaya V, Yushko L, Nikolaev A et al (2007) New approaches to the removal of protein-bound toxins from blood plasma of uremic patients. Artif Cells Blood Substit ImmobU Biotechnol 3 287-308... 

Fig. 29.3 Lack of notable influence of exhaustive dialysis and conventional DHP on the melting curves of HSA extracted from blood plasma of uremic and cirrhotic patients...

Serum albumin is a natural transporter of hydrophobic metabolites it binds toxic ligands reversibly, and if the ligand can be removed from the complex then the melting curve of unloaded albumin should return to that of pure protein. However this remains a difficult task, and neither exhaustive dialysis, nor the use of conventional carbonic sorbents, influence the shape of melting curves of albumin isolated from blood plasma of uremic patients and patients with hepatic insufficiency (Fig. 29.3) [9]. 

Fig. 29.10 Melting curves of HSA from healthy donors (a) extracted from blood plasma of cirrhotic (b) and uremic patients (c) before and after (bl, cl) contact with HSGD hemosorbent...

Valacyclovir is generally well tolerated, although nausea, vomiting, or rash occasionally occur. At high doses, confusion, hallucinations, and seizures have been reported. AIDS patients who received high-dosage valacyclovir chronically (ie, 8 g/d) had an increased incidence of gastrointestinal intolerance as well as thrombotic thrombocytopenic purpura and hemolytic-uremic syndrome this dose was associated with confusion and hallucinations in transplant patients. 

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