Enzymes elevation

Fever, rigors, chills, malaise headaches, myalgia Nausea, emesis Neutropenia Hepatic enzyme elevation Cutaneous—alopecia, transient, mild rashlike reaction Acetaminophen (APAP). NSAID if APAP is not effective. Meperidine for severe chills and rigors. Bedtime administration. 5-HT3 antagonist, prochlorperazine, metoclopramide, fluids Weekly complete blood count reduce dose by 30-50% Liver function tests (LFTs) weekly withhold treatment until LFTs normalize restart at 30-50% dose reduction reversible on dose reduction or cessation. Interferon is contraindicated in patients with psoriasis because exacerbation of psoriasis has been noted during IFN therapy. 

Tumor response is measured by clinical chemistry (e.g., liver enzyme elevation in patients with hepatic metastases) or imaging techniques (e.g., bone scans or chest x-rays). 

Literature supports this drug (drug combination) and pattern of liver +2 enzyme elevation... 

Relative Patterns of Hepatic Enzyme Elevation versus Type of Hepatic Lesion... 

Statins [3,16] 20-60 20 0 2-10 Muscle toxicity, liver enzyme elevation... 

Primates offer all of the possible dosing routes available in humans, but body size often limits dosing volumes. If volumes for subcutaneous or intramuscular injections exceed those suggested above, enzyme elevations [particularly alanine aminotransferase (ALT) and aspartate aminotransferase (AST)] are frequently observed (unpublished results). Continuous infusion techniques in alert animals are available in some laboratories either through use of programmable backpack pumps or jacket-and-tether systems (Perkin and Stejskal, 1994). 

Phosphorylation of cardiac calcium-channel proteins increases the probability of channel opening during membrane depolarization. It should be noted that cAMP is inactivated by phosphodiesterase. Inhibitors of this enzyme elevate intracellular cAMP concentration and elicit effects resembling those of epinephrine. 

Hepatotoxicity Available clinical data show no evidence of pioglitazone- and rosiglitazone-induced hepatotoxicity or ALT elevations. It is recommended that patients undergo periodic monitoring of liver enzymes. Check liver enzymes prior to the initiation of therapy in all treated patients. Do not initiate therapy in patients with increased baseline liver enzyme levels (ALT more than 2.5 times the ULN). In patients with normal baseline liver enzymes, it is recommended that liver enzymes be monitored every 2 months for the first 12 months and periodically thereafter. Evaluate patients with mildly elevated liver enzymes (ALT levels less than or equal to 2.5 times the ULN) at baseline or during therapy to determine the cause of the liver enzyme elevation. Proceed with caution in the initiation of, or continuation of, therapy in patients with mild liver enzyme elevations and include appropriate close clinical follow-up, including more frequent liver enzyme monitoring, to determine if the liver enzyme elevations resolve or worsen. If at any time ALT levels increase to more than 3 times the ULN, recheck liver enzyme levels as soon as possible. If ALT levels remain more than 3 times the ULN, discontinue therapy. 

Liver Methotrexate causes hepatotoxicity, fibrosis, and cirrhosis, but generally only after prolonged use. Acutely, liver enzyme elevations are frequent, usually transient and asymptomatic, and also do not appear predictive of subsequent hepatic disease. Liver biopsy after sustained use often shows histologic changes, and fibrosis and cirrhosis have occurred these latter lesions often are not preceded by symptoms or abnormal liver function tests (see Precautions). For this reason, periodic liver biopsies are usually recommended for psoriatic patients who are under long-term treatment. Persistent abnormalities in liver function tests may precede appearance of fibrosis or cirrhosis in the RA population. 

Figure 6. Effects of various treatments or manipulations upon levels of phenylalanine ammonia-lyase (PAL), chalcone synthase (CHS), and the separately compartmented isozymes of DAHP synthase and chorismate mu-tase. Upwardly pointed arrows indicate a positive response (enzyme elevation) to the indicated treatment, whereas horizontal arrows indicate no change in enzyme level. References documenting the results shown are line 1 (54 our results with DAHP synthase and chorismate mutase isozymes) line 2 (49,55) line 3 (49,50,56) line 4 (57) line 5 (51) line 6 (52).

Isoniazid (child 10 mg/kg up to) 300 mg orally, for 6 months 15 mg/kg orally, for 6 months 15 mg/kg orally, for 6 months Hepatic enzyme elevation Hepatitis Peripheral neuropathy CNS (mild) Drug interactions Hepatitis risk increases with age and alcohol consumption. Pyridoxine can prevent peripheral neuropathy... 

Mild to moderate side effects, including nausea, vomiting, abdominal pain, diarrhea, anorexia, and headache, occur in up to 33% of patients taking this drug. Skin rash and discoloration, fever, reversible male infertility, and liver enzyme elevation occur less frequently. Rare hematological abnormalities, such as agranulocytosis, aplastic anemia, hemolytic anemia, neutropenia, or other blood dyscrasias, can be fatal. Hypersensitivity reactions occur rarely. 

Fluconazole is well tolerated. Nausea, vomiting, abdominal pain, diarrhea, and skin rash have been reported in fewer than 3% of patients. Asymptomatic liver enzyme elevation has been described, and several cases of drug-associated hepatic necrosis have been reported. Alopecia has been reported as a common adverse event in patients receiving prolonged high-dose therapy. Coadministration of fluconazole with phenytoin results in increased serum phenytoin levels. 

Itraconazole is usually well tolerated but can be associated with nausea and epigastric distress. Dizziness and headache also have been reported. High doses may cause hypokalemia, hypertension, and edema. Itraconazole, unlike ketoconazole, is not associated with hormonal suppression. Hepatotoxicity occurs in fewer than 5% of cases and is usually manifested by reversible Uver enzyme elevations. 

Nausea, vomiting, and anorexia occur commonly with ketoconazole, especially when high doses are prescribed. Epigastric distress can be reduced by taking ketoconazole with food. Pruritis and/or allergic dermatitis occurs in 10% of patients. Liver enzyme elevations during therapy are not unusual and are usually reversible. Severe ketoconazole-associated hepatitis is rare. 

Topical use results in therapeutic drug concentrations in the epidermis and mucous membranes less than 10% of the drug is systemically absorbed. Although clotrimazole is generally well tolerated, local abdominal cramping, increased urination, and transient liver enzyme elevations have been reported. 

When 5-FC is prescribed alone to patients with normal renal function, skin rash, epigastric distress, diarrhea, and liver enzyme elevations can occur. When it is prescribed to patients with renal insufficiency or to patients receiving concurrent amphotericin B therapy, blood levels of 5-FC may rise, and bone marrow toxicity leading to leukopenia and thrombocytopenia is common. 5-FC serum levels should be closely monitored in patients with renal insufficiency. Because of baseline leukopenia, 5-FC is often not tolerated by end-stage HIV-infected patients with disseminated fungal infection. 

Nausea and mucosal ulcers are the most common toxicities. Progressive dose-related hepatotoxicity in the form of enzyme elevation occurs frequently, but cirrhosis is rare (< 1%). Liver toxicity is not related to serum methotrexate concentrations, and liver biopsy follow-up is only recommended every 5 years. A rare hypersensitivity-like lung reaction with acute shortness of breath is documented, as are pseudolymphomatous reactions. The incidence of gastrointestinal and liver function test abnormalities can be reduced by the use of leucovorin 24 hours after each weekly dose or by the use of daily folic acid, although this may decrease the efficacy of the methotrexate. This drug is contraindicated in pregnancy. 

Paromomycin sulfate is an aminoglycoside antibiotic that until recently was used in parasitology only for oral therapy of intestinal parasitic infections (see previous text). It has recently been developed for the treatment of visceral leishmaniasis. A phase 3 trial in India showed excellent efficacy for this disease, with a daily intramuscular dosage of 11 mg/kg for 21 days yielding a 95% cure rate, and noninferiority compared with amphotericin. The drug was registered for the treatment of visceral leishmaniasis in India in 2006. In initial studies, paromomycin was well tolerated, with common mild injection pain, uncommon ototoxicity and reversible liver enzyme elevations, and no nephrotoxicity. Paromomycin is much less expensive than liposomal amphotericin or miltefosine, the other promising new therapies for visceral leishmaniasis. 

Acitretin (Soriatane), a metabolite of the aromatic retinoid etretinate, is quite effective in the treatment of psoriasis, especially pustular forms. It is given orally at a dosage of 25-50 mg/d. Adverse effects attributable to acitretin therapy are similar to those seen with isotretinoin and resemble hypervitaminosis A. Elevations in cholesterol and triglycerides may be noted with acitretin, and hepatotoxicity with liver enzyme elevations has been reported. Acitretin is more teratogenic than isotretinoin in the animal species studied to date, which is of special concern in view of the drug s prolonged elimination time (more than 3 months) after chronic administration. In cases where etretinate is formed by concomitant administration of acitretin and ethanol, etretinate may be found in plasma and subcutaneous fat for many years. 

Other experiments indicated that the fraction of tRNA that is charged with an amino acid is a crucial factor in the attenuation response. This has been examined in vivo by comparing the trp operon enzyme levels in trpRT strains that are otherwise normal with strains that are defective in some respect in charged tRNATrp. Such structural defects in tRNATrp or in the charging enzyme elevates expression, probably by permitting polymerase to transcribe through the attenuator. 

Cardiac enzyme elevation (creatine kinase-MB, cardiac troponin) may occur on average in 20% to 30% of patients after PCI and is associated with adverse clinical outcomes in the short- and long-term (64), Magnetic resonance imaging... 

Zhalkovsky B, Walker D, Bourgeois JA. Seizure activity and enzyme elevations after venlafaxine overdose. J Clin Psychopharmacol 1997 17(6) 490—1. 

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