Hypoalbuminemia

Equation to adjusted measured phenytoin levels in the setting of hypoalbuminemia... 

Albumin 12.5-25 g IV every 8-24 h ° Use only if diuretics have been maximized ° May be warranted in patients with severe hypoalbuminemia... 

Correct serum calcium in the presence of hypoalbuminemia ° Corrected serum calcium (mg/dL) = measured serum... 

Crohn s disease Leukocytosis, decreased hematocrit/hemoglobin, elevated ESR, guaiac-positive stool, (+) ariti-5accharomyces cerevisiae antibodies (up to 50% of patients), hypoalbuminemia with severe disease... 

The pathophysiologic mechanisms of portal hypertension and of cirrhosis itself are entwined with the mechanisms of ascites (Fig. 19-3). Cirrhotic changes and the subsequent decrease in synthetic function lead to a decrease in production of albumin (hypoalbuminemia). Albumin is the major intravascular protein involved in maintaining oncotic pressure in the vascular system low serum albumin levels and increased capillary permeability allow fluid to leak from the vascular space into body tissues. This can result in peripheral edema, ascites, and fluid in the pulmonary system. The obstruction of hepatic sinusoids and... 

Causes of hypocalcemia include hypoparathyroidism, hypomagnesemia, alcoholism, hyperphosphatemia, blood product infusion (due to chelation by the citrate buffers), chronic renal failure, vitamin D deficiency, acute pancreatitis, alkalosis, and hypoalbuminemia. Medications that cause hypocalcemia include phosphate replacement products, loop diuretics, phenytoin (Dilantin, available as generic), pheno-barbital (available as generic), corticosteroids, aminoglycoside antibiotics, and acetazolamide (available as generic).34,39,42... 

Leukocytosis, hypoalbuminemia, and fecal leukocytes are nonspecific but suggestive of C. difficile infection. 

Diarrhea Drug related Antibiotic-induced bacterial overgrowth Hyperosmolar medications administered via feeding tubes Antacids containing magnesium Malabsorption Hypoalbuminemia/gut mucosal atrophy Pancreatic insufficiency Inadequate GIT surface area Rapid GIT transit Radiation enteritis Tube feeding related Rapid formula administration Formula hyperosmolalty Low residue (fiber) content Lactose intolerance Bacterial contamination... 

Trimetrexate -antifolate antimetabolite -bone marrow suppression -mucocutaneous effects (mucositis, stomatitis) -nausea and vomiting -fever -maculopapular rash—usually self-limited -anorexia, malaise -above toxicities increased in patient with hypoalbuminemia (<3.5)... 

Pruritus, jaundice, palmar erythema, spider angiomata, hyperpigmentation Gynecomastia, reduced libido Ascites, edema, pleural effusion, and respiratory difficulties Malaise, anorexia, and weight loss Encephalopathy Laboratory tests Hypoalbuminemia Elevated prothrombin time Thrombocytopenia Elevated alkaline phosphatase... 

AED pharmacokinetic data are summarized in Table 52-3. For populations known to have altered plasma protein binding, free rather than total serum concentrations should be measured if the AED is highly protein bound. Conditions altering AED protein binding include chronic renal failure, liver disease, hypoalbuminemia, burns, pregnancy, malnutrition, displac-... 

Absorption may be saturable. Absorption is affected by particle size, and the brand should not be changed without careful monitoring. Food may slow absorption. The intramuscular route is best avoided, as absorption is erratic. Fosphenytoin can safely be administered IV and intramuscularly. Equations are available to normalize the phenytoin concentration in patients with hypoalbuminemia or renal failure. 

The free fraction may increase as the total concentration increases, and free concentrations may be more useful than total concentrations, especially at higher concentrations or in patients with hypoalbuminemia. Protein binding is decreased in patients with head trauma. 

Fluid requirements increase with increased insensible or GI losses, fever, sweating, and increased metabolism. Fluid requirements decrease with kidney or cardiac failure and hypoalbuminemia with starvation. 

Hypocalcemia associated with hypoalbuminemia requires no treatment because ionized plasma calcium concentrations are normal. 

Gram-negative bacteremia Hypoalbuminemia Increased age Liver disease Obstructive jaundice Preexisting kidney disease Poor nutrition... 

Therapeutic range of phenytoin is 4-10 mcg/mL in presence of significant azotemia and/or hypoalbuminemia. 

Renal/Hepatic function impairment- Because of an increased fraction of unbound phenytoin in patients with renal or hepatic disease, or in those with hypoalbuminemia, interpret total phenytoin plasma concentrations with caution. Unbound phenytoin concentrations may be more useful in these patients. After IV administration, fosphenytoin clearance to phenytoin may be increased without a similar increase in phenytoin clearance. This has the potential to increase the frequency and severity of adverse events. 

Following intravenous injection of 0-2.8 pCi/kg (104,000 Bq/kg) thorium-227 in a solution of citric acid-sodium citrate buffer in dogs, an increase in serum alkaline phosphatase measurements and hypoalbuminemia and hyperglobulinemia were observed (Stevens et al. 1967). No effects on the levels of serum glutamic pyruvic transaminase (SGPT) or serum glutamic oxaloacetic transaminase (SGOT) were found. 

Drug distribution in elderly patients may be altered by hypoalbuminemia, qualitative changes in drug-binding sites, reductions in relative muscle mass, increases in the proportion of body fat, and decreases in total body water. The plasma level of free, active drug is often a direct function of the extent of drug binding to plasma proteins. There is a well-documented age-dependent decline (about 20%) in plasma albumin concentration in humans due to a reduced rate of hepatic albumin... 

Laxative abuse includes symptoms of abdominal pain, weakness, fatigue, thirst, vomiting, edema, bone pain, fluid and electrolyte imbalance, hypoalbuminemia, and syndromes that mimic colitis. 

Use with caution in older patients with Cognitive impairment. Hepatic impairment, End-stage renal disease, Hypoalbuminemia, Bradycardia, 2nd or 3rd degree heart block. Severe cardiovascular disease (when using IV), Osteoporosis, Unsteady gait. Urinary incontinence... 

An 8-year-old child with grand mal seizures experiences nystagmus while on 200 mg/day of long-term phenytoin treatment, given in three divided doses. A steady-state phenytoin concentration of 5.0 mg/L is measured (therapeutic range, 8-20 mg/L). Beside normal laboratory results, it was noted that the child had profound hypoalbuminemia. Free (unbound) phenytoin concentration was 2.4 mg/L (therapeutic range 0.2-2 mg/L). 

Liver disease is often associated with edema and ascites in conjunction with elevated portal hydrostatic pressures and reduced plasma oncotic pressures. Mechanisms for retention of Na+ by the kidney in this setting include diminished renal perfusion (from systemic vascular alterations), diminished plasma volume (due to ascites formation), and diminished oncotic pressure (hypoalbuminemia). In addition, there may be primary Na+ retention due to elevated plasma aldosterone levels. 

Phenytoin is highly bound to plasma proteins. The total plasma level decreases when the percentage that is bound decreases, as in uremia or hypoalbuminemia, but correlation of free levels with clinical states remains uncertain. Drug concentration in cerebrospinal fluid is proportionate to the free plasma level. Phenytoin accumulates in brain, liver, muscle, and fat. 

The mechanism of pleural effusion in the present case was suspected to be increased capillary permeability due to alprostadil hypoalbuminemia probably also contributed. 

The binding sites of the protein are not unlimited and are subject to saturation. When this occurs, toxicity may develop following further drug administration, because the later portion of the drug remains free. Consistent with this view is the observation that toxic manifestations of drugs are quite frequent and considerably higher in individuals suffering from hypoalbuminemia, or altered plasma and tissue protein concentrations, or both. 

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