Liver function impairment

Most, if not all, occupational illnesses associated with 2,4,5-T (such as chloracne) have been found to be the result of product contamination with TCDD. TCDD is extremely toxic to animals, and exposure has also been associated with liver function impairment, peripheral neuropathy, personality changes, porphyria cutanea, hypertrichosis, and hyperpigmentation in humans. TCDD is a chlorinated dioxin, one of a large number of related compounds referred to as dioxins it has no functional use and is not intentionally produced. It has been identified as the responsible toxic agent in several industrial disasters, such as accidental releases at Nitro, WV in 1949, and at Seveso, Italy in 1976. " The role of dioxin contaminants must also be considered in the discussion of 2,4,5-T toxicology. 

Liver function impairment Therapy with pioglitazone/metformin should not be initiated if the patient exhibits clinical evidence of active liver disease or increased serum transaminase levels (ALT greater than 2.5 times the ULN) at start of therapy. Liver enzyme monitoring is recommended in all patients prior to initiation of therapy with pioglitazone/metformin and periodically thereafter. 

Liver function impairment - In patients with progressive ALT increases above baseline values, reduce the dose of peginterferon alfa-2a to 135 meg. Immediately discontinue therapy if ALT increases are progressive despite dose reduction or are accompanied by increased bilirubin or evidence of hepatic decompensation. 

Three studies examined the mediating effect of phenobarbital on white phosphorus-induced liver function impairment. Pre-treatment with four or five intraperitoneal injections of phenobarbital showed no effect on white phosphorus-induced triglyceride accumulation at 12 hours after white phosphorus administration (Pani et al. 1972), but had an antagonistic effect on white phosphorus-induced increases in BSP retention at 24 hours after treatment with white phosphorus (Hurwitz 1972). The antagonistic effect of phenobarbital pretreatment on white phosphorus-induced BSP retention disappeared by 48 hours after white phosphorus administration. Another study conducted by Hurwitz (1972) showed the antagonistic effect of 4 daily intraperitoneal post-treatments with phenobarbital on white phosphorus-induced mortality. 

Caution in impaired liver function, impaired renal function... 

The influence of age on metabolic clearance is less clear than its influence on renal function. Metabolic clearance is more variable between individuals because of the genetic control and the influence of environmental factors on the metabolic capacity. The term metabolism also encompasses many different enzyme reactions that might be influenced to different extents by age, liver disease, or genetic variables. Unlike renal disease, in which creatinine clearance provides a reasonable estimate of kidney function, not one good indicator exists for the degree of liver function impairment with respect to drug metabolizing capacity. 

MW-2884 (10-methoxy-4//-benzo-(4,5)-cycloheptathio-phene-4-glindene acetic acid) is an inhibitor of monokine release. In 12 patients with rheumatoid arthritis it caused gastrointestinal disturbances, temporary liver function impairment, and allergic skin reactions. One patient stopped taking it because of severe urticaria (1). 

Sulindac can cause toxic hepatitis, and several cases, some with positive rechallenge, have been described (27,28). A retrospective cohort study with secondary case-control analysis suggested that sulindac has a higher incidence of acute liver damage than all other NSAIDs, although the calculated risk is very low (27 per 100000 prescriptions) (29). Liver function impairment is generally mild and reversible. Analysis of spontaneous reports to the FDA and the Danish Committee on ADRs (SEDA-18, 103) has confirmed these data. 

Decreased liver function impairs metabolism of the medication... 

Babb and Kieraldo (1978) reported a case of cirrhosis and portal hypertension attributable to hypervitaminosis A in a 72-year-old male who had been taking 12 mg/day of retinol for 6-7 years. Meunter et al. (1971) reviewed 17 cases of chronic vitamin A toxicity in patients receiving 12.3-180 mg retinol equiv-alents/day for several months up to 9 years. Two patients showed marked liver function impairment at 2i and 12 years, respectively, after discontinuing retinol. Marked elevations of plasma lipid levels were also noted. Deuel (1957) reported that hypervitaminosis A is accompanied by hyperlipidemia involving most of the plasma lipid fractions. 

The dosage of flucytosine is 150—200 mg/kg orally in four portions every six hours. A 1% flucytosine solution has been developed for intravenous adrninistration. In some countries, a 10% ointment is also available. In patients with normal renal function, flucytosine is seldom toxic, but occasionally severe toxicity may be observed (leukopenia and thrombocytopenia). Plasma levels should be determined and the dose in patients with impaired renal function should be checked. Liver function tests (transaininases and alkaline phosphatase) should be performed regularly. In some patients with high flucytosine plasma levels, hepatic disorders have been observed (24). 

Some authorities question whether dmnkeimess can result from the inhalation of ethyl alcohol vapors. Experience has demonstrated that in any event such intoxication is indeed rare (281). There is no concrete evidence that the inhalation of ethyl alcohol vapor will cause cirrhosis. Liver function is definitely impaired during alcohol intoxication (282), making the subject more susceptible to the toxic effects of chlorinated hydrocarbons. 

In liver disease, for example, the ability to metabolize or detoxify a specific type of drug may be impaired. If the average or normal dose of the drug is given, the liver may be unable to metabolize the drug at a normal rate Consequently, the drug may be excreted from the body at a much slower rate than normal. The primary health care provider may then decide to prescribe a lower dose and lengthen the time between doses because liver function is abnormal. 

It is important to use the tetracyclines cautiously in patients witii renal function impairment, hi addition, doses greater that 2 g d can be extremely damaging to die liver. The nurse should carefully check die expiration dates of die tetracyclines before administration because degradation of the tetracyclines can occur after degradation, the agents are highly toxic to the kidneys. 

This drug is used cautiously in patients with peripheral vascular disease, neuropathy, chronic pancreatitis, or impaired liver function. Didanosine is a Pregnancy Category B drug and is used cautiously during pregnancy and lactation. There may be a decrease in the effectiveness of dapsone in preventing Pneumocystis carinii pneumonia when didanosine is administered with dapsone Use of didanosine with zalcitabine may cause additive neuropathy. Absorption of didanosine is decreased when it is administered with food. 

The MAOI antidepressant drag s are contraindicated in patients widi known hypersensitivity to die drug s, liver and kidney disease, cerebrovascular disease, hypertension, or congestive heart failure and in die elderly. These drag s are given cautiously to patients witii impaired liver function, history of seizures, parkinsonian symptoms, diabetes, or hyperthyroidism. 

The oral antidiabetic drugs are contraindicated in patients with known hypersensitivity to tiie drugs, DKA, severe infection, or severe endocrine disease. The first generation sulfonylureas (chlorpropamide, tolazamide, and tolbutamide) are contraindicated in patients with coronary artery disease or liver or renal dysfunction. Other sulfonylureas are used cautiously in patients with impaired liver function because liver dysfunction can prolong the drug s effect. In addition, the sulfonylureas are used cautiously in patients with renal... 

For a variety of reasons, lipid—mainly as triacylglycerol—can accumulate in the hver (Figure 25—6). Extensive accumulation is regarded as a pathologic condition. When accumulation of lipid in the Ever becomes chronic, fibrotic changes occur in the cells that progress to cirrhosis and impaired liver function. 

Fatty infiltration of the liver. In this pathology, the triglyceride concentration in the liver is 10-fold superior to the norm. The accumulation of fat in the cyto-plasm of hepatic cells leads to an impaired liver function. The causes of this pathol-ogy are numerous one of these may be a deficiency in lipotropic factors and the associated therewith synthesis of excess triglycerides. 

The complete preparation required 50 min. The PET scans with 160, performed in normal and mutant rats, showed129,132 that N-[l-nC]acetyl-LTE4 may be used to study various human diseases with impaired bile flow and reduced liver function. 

Ammonia has deleterious effects on brain function by direct and indirect mechanisms. Concentrations of ammonia in the 1-2 mmol/1 range, equivalent to those reported in the brain in liver failure, impair postsynaptic inhibition in cerebral cortex and brainstem by a direct effect on Cl extrusion from the postsynaptic neuron. Millimolar concentrations of ammonia also inhibit excitatory neurotransmission. Synaptic transmission from Schaffer collaterals to CA1 hippocampal neurons is reversibly depressed by 1 mmol/1 ammonia, and the firing of CA1 neurons by iontophoretic application of glutamate is inhibited by 2 mmol/1 ammonia [10],... 

No measurable difference from controls at low dose impaired liver function at high dose (Khasawinah etal. 1989)... 

The adverse effects of antiandrogens are gynecomastia, hot flushes, GI disturbances, liver function test abnormalities, and breast tenderness. GI disturbances consist of diarrhea for flutamide and bicalutamide and nausea or constipation for nilutamide. Flutamide is also associated with methemoglobinemia, whereas nilutamide causes visual disturbances (impaired dark adaptation), alcohol intolerance, and interstitial pneumonitis. 

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