Hepatic failure/insufficiency

Hepatic function impairment Elevations of hepatic enzymes and hepatic failure have been reported in association with dipyridamole administration. Dipyridamole can be dosed without restriction as long as there is no evidence of hepatic failure. Avoid aspirin in patients with severe hepatic insufficiency. 

Hepatic function impairment Hepatitis including cases resulting in hepatic failure and death has been reported in patients treated with indinavir. Patients with hepatic insufficiency because of cirrhosis should have the dosage of indinavir lowered because of decreased metabolism. 

Gastric distress (nausea and vomiting) is one of the most frequently reported adverse reactions. Bladder irritation (e.g., dysuria, polyuria, hematuria, and urgency) may occur. The mandelic salt can crystallize in urine if there is inadequate urine flow and should not be given to patients with renal failure. Patients with preexisting hepatic insufficiency may develop acute hepatic failure due to the small quantities of ammonia formed during methenamine hydrolysis. 

Most of the drug is inactivated either by conjugation with glucuronic acid (principally in the liver) or by reduction to inactive aryl amines. Active chloramphenicol (about 10% of the total dose administered) and its inactive degradation products (about 90% of the total) are eliminated in the urine. A small amount of active drug is excreted into bile and feces. The systemic dosage of chloramphenicol need not be altered in renal insufficiency, but it must be reduced markedly in hepatic failure. Newborns less than a week old and premature infants also clear chloramphenicol less well, and the dosage should be reduced to 25 mg/kg/d. 

Contraindications to interferon alfa therapy include hepatic decompensation, autoimmune disease, and history of cardiac arrhythmia. Caution is advised in the setting of psychiatric disease, epilepsy, thyroid disease, ischemic cardiac disease, severe renal insufficiency, and cytopenia. Alfa interferons are abortifacient in primates and should not be administered in pregnancy. Potential drug-drug interactions include increased theophylline levels and increased methadone levels. Co-administration with didanosine is not recommended because of a risk of hepatic failure, and co-administration with zidovudine may exacerbate cytopenias. 

The oral administration of neomycin (usually in combination with erythromycin base) has been employed primarily for preparation of the bowel for surgery. For therapy of hepatic encephalopathy, a daily dose of 4 to 12 g (in divided doses) by mouth is given, provided that renal function is normal. Because renal insufficiency is a complication of hepatic failure and neomycin is nephrotoxic, it is used rarely for this indication. Lactulose is a much less toxic agent and is preferred. 

However, encephalopathies with a metabohc basis tend to be the most problanatic for infants or children, with functional outcomes dependent upon timely and pradent interventions. Three varieties of metabolic encephalopathy in children are discussed here. The first two are closely related. Inborn (genetic) errors of metabolism can present in the newborn as severe encephalopathy from hyperammonemia alone. When a metabolic error presents months to years later, a degree of hepatic insufficiency may complicate the metabolic derangement. In acute or fulminant hepatic failure of any etiology (i.e., infections, drug-induced, toxin-related), the rise in serum ammonia may be only moderate but other factors contribute to the ensuing encephalopathy, which may be devastating within days. 

HE is a central nervous system disturbance with a wide range of neuropsychiatric symptoms associated with hepatic insufficiency and liver failure. 

Renal failure and hepatic insufficiency - Measure serum levels to provide additional guidance for adjusting dosage however, this may not be practical. 

Renai/Hepatic function impairment The safety and pharmacokinetics of rimantadine in renal and hepatic insufficiency only have been evaluated after single dose administration. In a single dose study of patients with anuric renal failure, the apparent clearance was approximately 40% lower and the elimination half-life was 1.6-fold greater than that in healthy controls. In a study of 14 people with chronic liver disease (mostly stabilized cirrhotics), no alterations in the pharmacokinetics were observed after a single dose of rimantadine. However, the apparent clearance of rimantadine following a single dose to 10 patients with severe liver dysfunction was 50% lower than that reported for healthy subjects. Because of the potential for accumulation of rimantadine and its metabolites in plasma, exercise caution when patients with renal or hepatic insufficiency are treated with rimantadine. 

Hepatic function impairment Give with caution in patients with mild to moderate hepatic insufficiency. Consider a dosage reduction to 300 mg once daily for patients with moderate hepatic insufficiency (Child-Pugh class B) who have not experienced virologic failure. Do not use atazanavir in patients with severe hepatic insufficiency (Child-Pugh class C). 

Remifentanil, recently approved for use in the United States and Europe, is the first truly ultra-shortacting opioid. Remifentanil s uifique ester linkage allows it to be rapidly degraded to an inactive carboxylic acid metabolite by nonspecific esterases found in tissue and red blood cells. Since it is not a good substrate for plasma pseudocholinesterase, deficiency of the enzyme does not influence its duration of action. Also, hepatic and renal insufficiencies do not influence remifentanil s pharmacokinetics, so it is useful when liver or kidney failure is a factor. Because of its rapid clearance following infusion, remifentanil has gained popularity as an agent for maintenance of anesthesia when an IV technique is practical. 

Adverse effects are gastritis, hematuria, chemical cystitis and skin rash. It is contraindicated in renal failure and hepatic insufficiency. 

Diseases that directly affect hepatic integrity include cirrhosis, viral infections, and collagen vascular diseases. Diseases that indirectly affect function include metabolic disorders (e.g., azotemia secondary to renal insufficiency) and cardiac disease. Although decreased left ventricular output can result in a decrease in hepatic arterial flow, right ventricular failure causes hepatic congestion, reducing the first-pass effect and delaying biotransformation. 

Isoniazid metabolites and a small amount of unchanged drug are excreted, mainly in the urine. The dose need not be adjusted in renal failure. Dose adjustment is not well defined in patients with severe preexisting hepatic insufficiency... 

Of 308 patients 73% had contraindications, risk factors, or intercurrent illnesses necessitating withdrawal of metformin (31) 19% had renal impairment, 25% heart failure, 6.5% respiratory insufficiency, and 1.3% hepatic impairment 51% had advanced coronary heart disease, 9.8% atrial fibrillation, 3.3% chronic alcohol abuse, 2% advanced peripheral arterial disease, and 0.7% were pregnant. 

Overhydration, edema, kidney insufficiency, nephrotic syndrome, poor dietary intake, impaired digestion, burns, congestive heart failure, cirrhosis, thyroid/adrenal/pituitary hormones, trauma, sepsis Chronic infection, cirrhosis, burns, enteropathies, nephrotic syndrome, cortisone, testosterone Cirrhosis, hepatitis, stress, inflammation, surgery, hyperthyroidism, cystic fibrosis, kidney dysfunction, zinc deficiency... 

There can be a pronounced increase in methionine and its derivatives in acute liver failure or in serious cases of cirrhosis. From these substances, mercaptans are formed in the colon (e. g. methandiol, ethandiol, dimethyldisul-phide). The cause of the sweetish aromatic smell of the expiratory air ( fresh-raw liver ) known as hepatic foetor (F. Umber, 1926 L. Schiff, 1946) is deemed to be volatile dimethylsulphide. (38) Its concentration does not correlate with the degree of encephalopathy or hepatic insufficiency, but with the intensity of the portosystemic shunts. Trimethylamine is also suspected of being a causative factor. (22) (s.pp 267, 379)... 

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