Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0027497 (nausea)
 23,468 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Chagas' disease (American trypanosomiasis) is an endemic parasitic disease in some areas of Latin America. About 16-18 million persons are infected with the aetiological agent of the disease, Trypanosoma cruzi, and more than 100 million are living at risk of infection. There are different modes of infection: (1) via blood sucking vector insects infected with T. cruzi, accounting for 80-90% of transmission of the disease; (2) via blood transfusion or congenital transmission, accounting for 0.5-8% of transmission; (3) other less common forms of infection, eg, from infected food or drinks or via infected organs used in transplants. The acute phase of the disease can last from weeks to months and typically is asymptomatic or associated with fever and other mild nonspecific manifestations. However, life-threatening myocarditis or meningoencephalitis can occur during the acute phase. The death rate for persons in this phase is about 10%. Approximately 10-50% of the survivors develop chronic Chagas' disease, which is characterized by potentially lethal cardiopathy and megacolon or megaoesophagus. There are two drugs available for the aetiological treatment of Chagas' disease: nifurtimox (Nfx) and benznidazole (Bz). Nfx is a nitrofurane and Bz is a nitroimidazole compound. The use of these drugs to treat the acute phase of the disease is widely accepted. However, their use in the treatment of the chronic phase is controversial. The undesirable side effects of both drugs are a major drawback in their use, frequently forcing the physician to stop treatment. The most frequent adverse effects observed in the use of Nfx are: anorexia, loss of weight, psychic alterations, excitability, sleepiness, digestive manifestations such as nausea or vomiting, and occasionally intestinal colic and diarrhoea. In the case of Bz, skin manifestations are the most notorious (e.g., hypersensitivity, dermatitis with cutaneous eruptions, generalized oedema, fever, lymphoadenopathy, articular and muscular pain), with depression of bone marrow, thrombocytopenic purpura and agranulocytosis being the more severe manifestations. Experimental toxicity studies with Nfx evidenced neurotoxicity, testicular damage, ovarian toxicity, and deleterious effects in adrenal, colon, oesophageal and mammary tissue. In the case of Bz, deleterious effects were observed in adrenals, colon and oesophagus. Bz also inhibits the metabolism of several xenobiotics biotransformed by the cytochrome P450 system and its reactive metabolites react with fetal components in vivo. Both drugs exhibited significant mutagenic effects and were shown to be tumorigenic or carcinogenic in some studies. The toxic side effects of both nitroheterocyclic derivatives require enzymatic reduction of their nitro group. Those processes are fundamentally mediated by cytochrome P450 reductase and cytochrome P450. Other enzymes such as xanthine oxidoreductase or aldehyde oxidase may also be involved.
 ...
PMID:Toxic side effects of drugs used to treat Chagas' disease (American trypanosomiasis). 1693 19

Colchicine, is an old and well-known drug, used for treatment of rheumatic diseases. Nausea, vomiting, abdominal pain, and diarrhea are the clinical symptoms of colchicine poisoning. Cardiotoxicity can lead to mortality. We report a case of colchicine intoxication complicated with complete heart block. A 9-year-old patient ingesting colchicine 0.4-0.5 mg/kg was transferred because of elevation of liver enzymes, and deterioration of kidney functions and cytopenia. History of colchicine ingestion had been unknown at time of admission. After initial fluid and electrolyte treatment electrolyte imbalance ameliorated but kidney and liver functions worsened. In the third day of admission (7th day of ingestion), she confessed taking colchicine pills. Her state of consciousness became comatose and endotracheal intubation required. She developed complete heart block requiring temporary transvenous pacemaker implantation in the fifth day of admission. One day after pacemaker implantation, cardiopulmonary arrest developed again and remained completely unresponsive to CPR, and died. Cardiotoxicity of colchicine is leading cause of mortality. Tachycardia and conduction anomalies are not rare, but complete AV block in pediatric patient has never been reported. Although underlying mechanism is not known colchicine may have a direct toxic effect on conduction.
 ...
PMID:Acute colchicine intoxication complicated with complete AV block. 2718 5