Nausea drug-induced

Mercaptopurine (6-MP) is an oral purine analog that is converted to a ribonucleotide to inhibit purine synthesis. Mercaptopurine is converted into thiopurine nucleotides, which are catabolized by thiopurine S-methyltransferase (TPMT), which is subject to genetic polymorphisms and may cause severe myelosuppression. TPMT status may be assessed prior to therapy to reduce drug-induced morbidity and the costs of hospitalizations for neutropenic events. Mercaptopurine is poorly absorbed, with a time to peak concentration of 1 to 2 hours after an oral dose. The half-life is 21 minutes in pediatric patients and 47 minutes in adults. Mercaptopurine is used in the treatment of acute lymphocytic leukemia and chronic myelogenous leukemia. Significant side effects include myelosuppression, mild nausea, skin rash, and cholestasis. When allopurinol is used in combination with 6-MP, the dose of 6-MP must be reduced by 66% to 75% of the usual dose because allopurinol blocks the metabolism of 6-MP. 

Vasopressin is a peptide hormone produced by the hypothalamus and secreted by the posterior pituitary in response to stimulation. Normal stimuli for vasopressin release are hyperosmolarity and hypovolemia, with thresholds for secretion of greater than 280 mOsm/kg and greater than 20% plasma volume depletion. A number of other stimuli, such as pain, nausea, epinephrine, and numerous drugs, induce release of vasopressin. Vasopressin release is inhibited by volume expansion, ethanol, and norepinephrine. The physiological effect of vasopressin is to promote free water clearence by altering the permeability of the renal collecting duct to water. In addition, it has a direct vasoconstrictor effect. Consequently, vasopressin results in water retention and volume restoration. In patients with septic shock, vasopressin is appropriately secreted in response to hypovolemia and to elevated serum osmolarity (R14). 

Hepatitis In 1 retrospective study of 7492 patients on rapidly absorbed aminosalicylic acid preparations, drug-induced hepatitis occurred in 38 patients (0.5%) in these 38, the first symptom usually appeared within 3 months of the start of therapy with a rash as the most common event followed by fever and much less freguently by Gl disturbances of anorexia, nausea, or diarrhea. 

Levodopa, the metabolic precursor of dopamine, is the most effective agent in the treatment of Parkinson s disease but not for drug-induced Parkinsonism. Oral levodopa is absorbed by an active transport system for aromatic amino acids. Levodopa has a short elimination half-life of 1-3 hours. Transport over the blood-brain barrier is also mediated by an active process. In the brain levodopa is converted to dopamine by decarboxylation and both its therapeutic and adverse effects are mediated by dopamine. Either re-uptake of dopamine takes place or it is metabolized, mainly by monoamine oxidases. The isoenzyme monoamine oxidase B (MAO-B) is responsible for the majority of oxidative metabolism of dopamine in the striatum. As considerable peripheral conversion of levodopa to dopamine takes place large doses of the drug are needed if given alone. Such doses are associated with a high rate of side effects, especially nausea and vomiting but also cardiovascular adverse reactions. Peripheral dopa decarboxylase inhibitors like carbidopa or benserazide do not cross the blood-brain barrier and therefore only interfere with levodopa decarboxylation in the periphery. The combined treatment with levodopa with a peripheral decarboxylase inhibitor considerably decreases oral levodopa doses. However it should be realized that neuropsychiatric complications are not prevented by decarboxylase inhibitors as even with lower doses relatively more levodopa becomes available in the brain. 

It causes antiemetic action by blocking dopamine (D receptors and it also increases gastric motility. It is absorbed orally but bioavailability is 15% due to first pass metabolism. It is completely biotransformed and metabolites are excreted in urine. It is used in nausea and vomiting in postoperative period, drug induced, radiation, uraemia, hepatitis, peptic ulcer. It is also useful in reflex oesophagitis. 

Cyclizine has antimuscarinic properties and is a potent anti-emetic, effective for the control of postoperative and drug-induced nausea and vomiting. It has been used to prevent motion sickness, although diphenhydramine and promethazine are more effective. It is available in oral and parenteral formulations. In contrast to many other first-generation antihistamines sedation is not marked. It is available in tablet form as the hydrochloride and in injectable form as the lactate. Because of its anticholinergic action, blurred vision and dry mouth are associated with clinical doses. When given by rapid intravenous injection tachycardia may be a problem. Meclozine is a related drug which, like cyclizine, is used primarily for motion sickness. 

Approximately 30% of patients using sulfasalazine discontinue the drug because of toxicity. Common adverse effects include nausea, vomiting, headache, and rash. Hemolytic anemia and methemoglobinemia also occur, but rarely. Neutropenia occurs in 1-5% of patients, while thrombocytopenia is very rare. Pulmonary toxicity and positive double-stranded DNA are occasionally seen, but drug-induced lupus is rare. Reversible infertility occurs in men, but sulfasalazine does not affect fertility in women. The drug does not appear to be teratogenic. 

The side effects of mycophenolate mofetil include diarrhea, abdominal pain, constipation, nausea/vomiting, acne, dyspnea, cough, peripheral edema, increased risk of infections, drug-induced fever, dizziness, headaches, leukopenia and anemia. 

Side effects. The common dose-related side effects of valproate include nausea, vomiting and gastrointestinal distress weight gain is frequent (estimated as high as 30%) and may be associated with a drug-induced decrease in the beta oxidation of fatty acids. Sedation is also frequent. Alopecia is an unusual side effect of valproate, possibly caused by an abnormal metabolite. Valproate has a number of metabolically linked side... 

Adding mirtazapine s 5FIT3 antagonism to venlafaxine or SSRIs may reverse drug-induced nausea, diarrhea, stomach cramps, and gastrointestinal side effects... 

Drug-induced anorexia, nausea, vomiting, and constipation are common side effects. 

Freeman AJ, Cullen MH. Advances in the management of cytotoxic drug-induced nausea and vomiting. J CUn Pharm Ther 1991 16(6) 411-21. 

A 44-year-old woman developed acute hepatitis while taking gatifloxacin for chronic sinusitis (23). After 5 days she developed nausea, lethargy, and abdominal pain, all of which progressed over the next few days. Liver function tests were abnormal, and the bilirubin peaked at 161 pmol/l. A percutaneous liver biopsy showed acute hepatitis with eosinophilic infiltrates, consistent with drug-induced hepatitis. 

Nausea and vomiting are frequent, perhaps in as many as one-third of all cases. In about half the cases, diarrhea is induced or existing diarrhea aggravated. Melena can occur, but this seems unlikely to be drug-induced (SED-11, 594). 

A 300 mg dose of rifabutin is usually well tolerated. Adverse effects include neutropenia, thrombocytopenia, rash, and gastrointestinal disturbances (nausea, flatulence). Myositis (12) and uveitis (13) are rarely observed. The drug-induced lupus-like syndrome has been linked in a few cases with rifampicin and rifabutin. 

A number of chemicals and drugs induce nausea and vomiting by an action involving the so-called chemoreceptor trigger zone (CTZ) within the area postrema of the brain. 

Many cytotoxic drugs used in the treatment of malignant disease are powerful emetics, and the distress caused by drug-induced nausea and vomiting is the... 

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