Hepatic disorders

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). 

Therapeutic Function Treatment of hepatic disorders Chemical Name 2-Acetamido-4-mercaptobutyric acid 7-lactone Common Name Acetylhomocystein thiolactone acetamido thiobutyrolactone Structural Formula o... 

In addition to the well-known iron effects on peroxidative processes, there are also other mechanisms of iron-initiated free radical damage, one of them, the effect of iron ions on calcium metabolism. It has been shown that an increase in free cytosolic calcium may affect cellular redox balance. Stoyanovsky and Cederbaum [174] showed that in the presence of NADPH or ascorbic acid iron ions induced calcium release from liver microsomes. Calcium release occurred only under aerobic conditions and was inhibited by antioxidants Trolox C, glutathione, and ascorbate. It was suggested that the activation of calcium releasing channels by the redox cycling of iron ions may be an important factor in the stimulation of various hepatic disorders in humans with iron overload. 

The ability of the liver to act as a depot for vitamin Bi2 (B28, G13) enables us to use this vitamin as an index of proper hepatic function. Hepatic disorders lead to an increased Bi2-binding in the serum (J5, R3), suggesting that the blood assumes a greater role in the conservation of B12. We have reported that patients with liver disease excreted invariably less than 10 fig of Bi2> 8 hours after a 50-[ig intramuscular load dose of the vitamin. In contrast, normal subjects excreted 24-40 pg, i.e., 50-80% of the vitamin in the same test (B14). These results were correlated with various chemical determinations indicative of hepatic disorders (Bl). In Table 16 the clinical diagnosis and the various liver-... 

B14. Baker, H., Pasher, I., Dolger, H., and Sobotka, H., Vitamin B12 excretion as index of hepatic disorder. Clin. Chem. 2, 328-330 (1956). 

Increased incidence of BUN is also found in subjects suffering from diabetes, hepatic disorders and gastrointestinal disturbances,... 

When the real problems with benoxaprofen emerged, however, they were more serious It was apparently killing elderly patients with hepatic disorders, inducing massive photosensitivity, and causing oncholysis (separation of the nail plate from the bed) in about 15% of patients. It seems probable that at least 70 elderly patients died, and many more people suf-fered. ° Shortly after its well-publicized entry into the U.S. market, the manufacturer of benoxaprofen voluntarily withdrew its product as it caused fatal cholestatic hepatitis. " This action immediately followed news of suspension of the license to sell benoxaprofen in the United Kingdom. ... 

Selective Drug Delivery for the Treatment of Other Hepatic Disorders... 

Vulnerability of the liver to injury necessitates routine evaluation of hepatic function in patients and asymptomatic individuals to avert or control adverse clinical conditions. Thus, a plethora of methods has been developed for the diagnosis of liver diseases and dysfunctions. One such method uses physical palpation to determine alterations or changes in the orientation of the liver, which provides valuable information about the organ status but the quality of information is subjective and imprecise [3]. Another common method for the diagnosis of more serious hepatic injuries involves liver biopsies coupled with biochemical tests to determine the extent of liver injury and prognosis [4-7]. However, in acute and some chronic hepatic disorders, dynamic and continuous hepatic function monitoring would be advantageous. 

Toxicology. Hexachlorobutadiene (HCBD) causes kidney damage including renal cancer in experimental animals it also produces central nervous system effects and causes hepatic disorders at very high concentrations. 

Enhanced anticoagulant effects Endogenous factors that may be responsible for increased PT/INR response include the following Blood dyscrasias cancer collagen vascular disease CHF diarrhea elevated temperature hepatic disorders (eg, infectious hepatitis, jaundice) hyperthyroidism poor nutritional state steatorrhea vitamin K deficiency. 

Antiadrenergic] Uses HTN Action Centrally acting antihypCTtensive Dose Adults. 250-500 mg PO bid-tid (max 2-3 g/d) or 250 mg-1 g IV q6-8h Peds. 10 mg/kg/24 h PO in 2-3 doses (max 40 mg/kg/24 h q6-12h) or 5-10 mg/kg/dose IV q6-8h to total dose of 20 0 mg/kg/24 h X in renal insuff/elderly Caution [B (PO), C (IV), +] Contra Liver Dz MAOIs Disp Tabs, inj SE Discolors urine initial transient sedation/drowsiness frequent, edema, hemolytic anemia, hepatic disorders Interactions T Effects W/ anesthetics, diuretics, levodopa, Li, methotrimeprazine, thioxanthenes, vasodilators, verapamil T effects OF haloperidol, Li, tolbutamide effects W/amphetamines, Fe, phenothiazine, TCAs ... 

Flumecinol (Gedeon Richter) Figure 8.86 Drugs for hepatic disorders. 

These drugs are best avoided in patients with cerebrovascular, cardiovascular and hepatic disorders. Some sympathomimetic effects may occur, mainly mild tremor and occasionally cardiac arrhythmias. Apparent anticholinergic effects may also occur but these are the result of sympathetic potentiation in tissues with dual cholinergic/adrenergic innervation, e.g. pupil. Sympatholytic effects can also occur, principally postural hypotension, because of synthesis of relatively inactive false transmitters, e.g. octopamine, in nerve terminals following inhibition of MAO and activation of alternative metabolic pathways. 

Chlordane Generalized convulsions, reproductive toxicity, birth defects, loss of consciousness, change in EEG pattern, hepatic disorders, neurologic disturbances, mutagenicity, carcinogenicity... 

Corticosteroids should be used cautiously in the presence of congestive heart failure, myocardial infarction, hypertension, diabetes mellitus, epilepsy, glaucoma, hepatic disorders, osteoporosis, peptic ulceration, and renal impairment. Children are more susceptible to these adverse effects. To avoid cardiovascular collapse, steroids must be given slowly by intravenous injection. Large doses produce Cushing s syndrome (with moon face and sometimes hirsutism). 

Duh, M. S., Walker, A. M., Pagano, M. Kronlund, K. (1998). Prediction and cross-validation of neural networks versus logistic regression using hepatic disorders as an example. Am J Epidemiol 147,407-13. 

Because of the reactions described above, and because carbamazepine is mostly metabolized in the liver, it should be used with caution in patients with hepatic disorders. 

There have been single cases of thrombocytopenia and a severe hemorrhagic diathesis with deficiency of coagn-lation factors due to a nitrofurantoin-induced hepatic disorder (44). Furthermore, nitrofurantoin experimentally inhibits ADP-induced platelet aggregation (45). 

Murphy KJ, Innis MD. Hepatic disorder and severe bleeding diathesis following nitrofurantoin ingestion. JAMA... 

Dossing M, Sonne J. Drug-induced hepatic disorders. Incidence, management and avoidance. Drug Saf 1993 9(6) 441-9. 

Do not use with patients who have hypersensitivity or severe renal disease. Use caution with patients with hepatic disorders. 

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