Hepatotoxic reactions

An Approach to Evaluating a Suspected Hepatotoxic Reaction Using a Clinical Diagnostic Scale... 

The patient is to be started on a drug that may cause a hepatotoxic reaction... 

Is the drug identified as one that may cause a predictable hepatotoxic reaction 0... 

This supports the supposition that severe hepatotoxic reactions to acarbose are idiosyncratic. 

Rumboldt Z, Bota B. Favorable effects of glibenclamide in a patient exhibiting idiosyncratic hepatotoxic reactions to both chlorpropamide and tolbutamide. Acta Diabetol Lat 1984 21(4) 387-91. 

The mechanism for most NSAID-induced hepatotoxic reactions is idiosyncratic, either immunological (hypersensitivity) or metabolic in type [29]. 

A review of adverse events related to herbal medicines reported in the medical literature from 1992 to 1996 has been compiled. This report highlights cases of hypersensitivity reactions, hepatotoxic reactions, and various types of renal damage associated with various herbal products. Some Chinese herbal preparations appear to be notorious for causing nephropathy.One of the more infamous adverse events related to the consumption of a dietary supplement was associated with the amino-acid L-tryptophan, touted for it s ability to reduce pain and promote sleep. 

Comparable reports have prompted a questionnaire investigation of 770 patients with type 2 diabetes at the start of acarbose therapy (51). Patients with one or more susceptibility factors for liver damage underwent ultrasonography and autoantibody assays. There was silent hver disease in 13% and 20 patients had a fatty liver without hepatic disease. In 15% of these patients there were slight reversible changes in transaminase activity after acarbose. This supports the supposition that severe hepatotoxic reactions to acarbose are idiosyncratic. 

Hepatotoxicity is the most important adverse effect of antituberculosis drug therapy. Isoniazid, rifampicin, and pyrazinamide are the main culprits. There is wide variability in the risk of hepatotoxic reactions reported from different parts of the world or in different populations (for example African-American women in the postpartum period) (SEDA-24, 353). 

Enhanced hepatotoxicity of conventional antituberculosis regimens has been reported in recipients of orthotopic hver transplants, which is not unexpected, because of bouts of organ rejection (25). The authors recommended ofloxacin for these patients on the basis of favorable outcome in six cases. A conventional antituberculosis induction regimen was used initially until hepatotoxicity developed in all six patients. Thereafter they were treated with a combination of ofloxacin and ethambutol, with apparent cure in all. It should be noted that most of the patients took isoniazid + rifampicin for almost 2 months, which is the usual period when hepatotoxic reactions occur. Perhaps one should evaluate substitution of rifampicin with ofloxacin from the very beginning in order to minimize hepatotoxicity, as well as interference with ciclosporin leading to graft rejection noted in an earlier study (26). 

Whatever the mechanisms might be, at present it is reasonable to look on clavulanate as the main contributor to the development of hepatotoxicity with co-amoxiclav. Hepatotoxicity has also been reported with clavulanate plus ticarcillin (34). So far, however, there has been no genetic evaluation of patients with hepatotoxic reactions after therapy with clavulanate and ticarcillin. 

In a study of isoniazid prophylactic therapy in Seattle, USA, only 11 patients of 11 141 had hepatotoxic reactions (25). The rate was 0.1% of those starting and 0.15% of those completing the course of therapy. The duration of therapy was not stated, but 10 of the 11 episodes occurred within 3 months of starting. 

However, in 531 eligible patients enrolled in a US Public Health Service Cooperative Trial of Short-Course Chemotherapy of Pulmonary Tuberculosis, of whom 58% were classified as alcoholic, although the alcoholics had more abnormal concentrations of aspartate transaminase before and during therapy, there was no significant difference between the alcoholics and non-alcoholics in the incidence of adverse reactions, including hepatotoxic reactions (92). The authors concluded that in the absence of clinically significant and persistent pretreatment abnormalities of hepatic function tests, rifampicin and isoniazid are not contraindicated in patients categorized as alcoholic. 

Powers BJ, Cattau EL Jr., and Zimmerman HJ (1986) Chlorzoxazone hepatotoxic reactions An analysis of 21 identified or presumed cases. Archives of Internal Medicine 146(6) 1183-1186. 

Tsagaropoou-Stinga H, Mataki-Emmanouilidon R, Karida-Kavalioti S, et al. Hepatotoxic reactions in children with severe tuberculosis treated with isoniazid-rifampin. Pediatr Infect Dis 1985 4 270-273. 

Most JA Markle GB. A nearly fatal hepatotoxic reaction to rifampin after halothane anesthesia. AmJSurg (1974) 127, 593-5. 

This serious and potentially life-threatening hepatotoxic reaction to protionamide is established, but the part played by the other drugs, particularly the rifampicin, is uncertain. Strictly speaking this may not be an interaction, bf protionamide is given the liver function should be very closely monitored in order to detect toxicity as soon as possible. 

Greving, I., V. Meister, C. Monnerjahn, K.M. Muller, and B. May. 1998. Chelidonium majus A rare reason for severe hepatotoxic reaction. Pharmacoepidemiol. Drug Safety 7(Suppl.) S66-S69. 

Many hepatotoxic reactions result from a common initiating event - the metabolic activation in the body of drugs that are chemically stable to potent alkylating or arylating agents. Paracetamol may be used as an example of this type of reaction (Prescott et al. 1974) if it is taken in excess (more than 15 g) with suicidal intent, it produces a clinical, laboratory and pathologic syndrome of severe, acute, and usually fatal hepatic necrosis. 

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