Hepatic intolerance

The 3-aminomethyl-l-pyrrolidinyl radical, which was considered to be bioiso-steric to piperazine [91], also produced highly active quinolones, which were however also found not to be tolerated. In trovafloxacin 16 [92], the 3-aminomethyl-l-pyrrolidinyl radical is integrated into a bicydic amine structural unit with a free amino group [(la,5a,6a)-6-amino-3-azabicyclo[3.1.0]hexane]. A correlation probably exists between the increased central nervous system (CNS) side effects obtained with this quinolone [93] and the 2,4-difluorophenyl radical in the 1-posi-tion. Severe hepatic intolerance reactions finally resulted in major restrictions on its use, which was then limited in the USA to severe clinical infections [68]. 

The glucan synthase inhibitor caspofungin (intravenous formulation) is new on the market for the treatment of invasive aspergillosis in patients whose disease is refractory to, or who are intolerant of, other therapies. During the clinical trials fever, infused vein complications, nausea, vomiting and in combination with cyclosporin mild transient hepatic side effects were observed. Interaction with tacrolismius and with potential inducer or mixed inducer/inhibitors of drug clearance was also seen. 

Indinavir (IDV) 200-, 333-, 800 mg q8hours Mild to moderate hepatic For unboosted IDV Nephrolithiasis Gl intolerance, CYP3A4 inhibitor... 

Potentially important laboratory abnormalities occurring with niacin therapy include elevated liver function tests, hyperuricemia, and hyperglycemia. Niacin-associated hepatitis is more common with sustained-release preparations, and their use should be restricted to patients intolerant of regular-release products. Niacin is contraindicated in patients with active liver disease, and it may exacerbate preexisting gout and diabetes. 

Initial dose 100 mg qd, increase by 100-mg increments/vi k until uric acid levels <6.5 mg/dL max 800 mg/d. Usual maintenance dosage 300 mg/d reduce in renal insufficiency rash, Gl intolerance common. Marrow suppression, hepatitis. 

Thiazides should be used cautiously in the presence of severe renal and hepatic disease, since azotemia and coma may result. The most important toxic effect associated with this class of diuretics is hypokalemia, which may result in muscular and central nervous system symptoms, as well as cardiac sensitization (see Hypokalemia). Periodic examination of serum electrolytes for possible imbalances is strongly recommended. Appropriate dietary and therapeutic measures for controlling hypokalemia are described later in this chapter. The thiazides also possess some diabetogenic potential, and although pancreatitis during thiazide therapy has been reported in a few cases, the major mechanism contributing to the potential for glucose intolerance is not known. 

The adverse effects that most frequently result in discontinuation of rifabutin include GI intolerance, rash, and neutropenia. Rifabutin levels will be increased with concurrent administration of fluconazole and clarithromycin, resulting in anterior uveitis, polymyalgia syndrome, and a yellowish-tan discoloration of the skin (pseudojaundice). Other adverse reactions are similar to those of rifampin, such as hepatitis, red-orange discoloration of body fluids, and drug interactions due to effects on the hepatic P450 cytochrome enzyme system. 

Thiacetazone is active against many strains of M. tuberculosis. It is not marketed in the United States. However, because of its low cost, it is used as a first-line agent in East Africa, especially in combination with compounds such as isoniazid. The most common side effects of thiacetazone include GI intolerance and development of rashes. It causes significant ototoxicity, especially when coadministered with streptomycin. Life-threatening hypersensitivity reactions, such as hepatitis, transient marrow aplastic syndromes, neutropenia, and thrombocytopenia, have been reported. 

Monitor carefully in first 3 mo of therapy for signs of intolerance/drug-induced hepatitis (rash, fever, jaundice, hepatomegaly)... 

Although all patients with depression should undergo a thorough medical evaluation, no specific tests are required before SSRI therapy is initiated. The usual starting doses of SSRIs are summarized in Table 2-1. These standard doses should be decreased by 50% in patients with hepatic disease and in elderly persons. In addition, patients with panic disorder or significant anxiety symptoms are often intolerant of the initial stimulating side effects that commonly occur with SSRI use. In these cases, the initial dose should be decreased... 

F. Role in therapy According to Micromedex, Roferon-A is recommended as the drug of choice in renal carcinoma and the chronic phase of chronic myelogenous leukemia. The role of Gleevec (Ima-tinib) in CML is yet to be determined, but it may replace the use of interferon alfa-2a. Roferon-A is an alternative (for unrespon-sive/intolerant patients) to current regimens of choice in hairy-cell leukemia, multiple myeloma, metastatic melanoma, and AIDS-related Kaposi s sarcoma. Other alpha interferons appear to have similar efficacy and can be used in lieu of Roferon-A in some instances. In particular, interferon alfa-2b (Intron) can be considered to have the same role as interferon alfa-2a in chronic hepatitis C, Kaposi s sarcoma, and hairy-cell leukemia. 

Fructose 1-phosphate aldolase B Hereditary fructose intolerance, vomiting, lethargy, failure to thrive, hepatic failure good prognosis with early diagnosis and fructose restriction... 

Glucose control Increased hepatic glucose production and glucose intolerance in hyperthyroidism impaired insulin action and glucose disposal in hypothyroidism... 

Iodoquinol should be taken with meals to limit gastrointestinal toxicity. It should be used with caution in patients with optic neuropathy, renal or thyroid disease, or nonamebic hepatic disease. The drug should be discontinued if it produces persistent diarrhea or signs of iodine toxicity (dermatitis, urticaria, pruritus, fever). It is contraindicated in patients with intolerance to iodine. 

Two individuals with serum triglyceride concentrations over 11.3 mmol/1 (1000 mg/dl) were referred to a pharma-cist-managed lipid clinic by their primary-care provider because of either treatment failure or intolerance of conventional therapies (14). Fish oils were used in one case in lieu of and in the other in addition to conventional treatments. Although fish oil has not been reported to cause hepatotoxicity, both of these patients had increased transaminases while taking fish oil. Whether fish oil truly causes hepatic injury remains to be elucidated. 

Hepatic remnant clearance impaired due to apo-E abnormality patients only express the apo-E2 isoform that interacts poorly with the apo-E receptor Elevated production of VLDL associated with glucose intolerance and hyperinsuLinaemia... 

Typically/ serum chemistries and renal/ hepatiC/ hema-tologiC/ electrolyte/ and mineral panels are included. A complete medical history (including a review of all body systems) and physical examination and a complete medication history (including allergies and intolerances) should be included. Use of prescription/ nonprescriptioii/ and alternative and complementary medications by study participants should be specifically documented. 

Suppression of bowel flora is thought by some to be useful in hepatic encephalopathy. Here, absorption of products of bacterial breakdown of protein (ammonium, amines) in the intestine lead to cerebral symptoms and even to coma. In acute coma, neomycin 6 g/d should be given by gastric tube as prophylaxis, 1-4 g/d may be given to patients with protein intolerance who fail to respond to dietary protein restriction (see also lactulose, p. 640). 

Wilson s disease, haemochromatosis, galactosaemia, glycogenosis type IV, ai-antitrypsin deficiency, tyrosin-aemia, idiopathic neonatal hepatitis, Niemann-Pick disease, Gaucher s disease, fructose intolerance, defective urea cycle, etc. 

Ritonavir/Norvir (RTV) 100 mg capsules 600 mg q. 12h (rarely used) Gl intolerance, hepatitis, pancreatitis, metabolic complications 3.3... 

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