Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0042963 (vomiting)
 31,883 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Apomorphine is a D1 and D2 dopamine receptor agonist with anti-parkinsonian properties qualitatively similar to those seen with L-dopa. It was first used in the treatment of Parkinson's disease by Schwab in the 1950s but owing to its short duration of action, the need for parenteral administration, and adverse reactions including nausea, vomiting, postural hypotension and sedation, it was not widely prescribed. In the early 1970s, Cotzias confirmed its potent anti-parkinsonian effects and that some of its secondary effects were diametrically opposite to those seen with L-dopa. The advent of peripheral dopamine receptor antagonist drugs, which counteract the unwanted effects of apomorphine, and the development of new drug delivery systems including insulin pens and ambulatory mini pumps have led to the resurrection of apomorphine for the treatment of Parkinson's disease. Over the last five years in Europe, the drug has proved to be a major advance in the treatment of refractory "on-off" oscillations in Parkinson's disease. It has also been used as a diagnostic test for dopaminergic responsiveness in Parkinson syndromes and tremors of uncertain aetiology. The drug has also proved particularly useful in dealing with certain "off-period" disabilities, including pain, bladder dysfunction, dystonia and gastro-intestinal symptoms. Continuous steady state infusion of apomorphine by mini-pump may reduce the severity of "on" phase dyskinesias over time. The drug has also proved useful in the clinical pharmacological investigation of the pathophysiology of the motor response to dopaminergic drugs in Parkinson's disease and the occurrence of involuntary movement sequences. Neuropsychiatric side-effects are relatively infrequent when compared with ergolene dopamine agonists.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Dopamine agonists in Parkinson's disease: a look at apomorphine. 850 Jul 83

The development of effective antiemetic prophylaxis is one of the most significant steps forward in the area of supportive care. Fifteen years ago, patients receiving chemotherapy had to face the fact that nausea and vomiting were inevitable adverse effects, which could only be partially prevented by treatment with antiemetics such as dopamine (DA) D2 receptor antagonists and corticosteroids. The first group of drugs specifically developed as antiemetics was the serotonin (5-hydroxytryptamine [5-HT](3)) receptor antagonists. These drugs have dramatically improved prophylaxis of chemotherapy-induced emesis, particularly when used in combination with a corticosteroid. This combination has resulted in a significant decrease in the number of patients vomiting, whereas the improvement in the prophylaxis of nausea has been less successful. Another group of antiemetics, the neurokinin (NK) 1 receptor antagonists, has recently been developed, and the first drug in this class, aprepitant, has been approved by the FDA and the EU authorities. Studies have showed that patients benefit from the use of this drug in combination with standard antiemetic therapy (5-HT 3 receptor antagonist plus a corticosteroid), both in the acute and delayed phase of nausea and vomiting induced by cisplatin-based chemotherapy. This development has not only led to improved efficacy but also to a decreased risk associated with the use of antiemetics. One of the problems with traditional antiemetics, for example, the DA D2 receptor antagonists, is the risk of unpleasant adverse effects including restlessness and dystonic reactions. To avoid these adverse effects, combination with benzodiazepines or antihistamines was necessary, often resulting in sedation. Modern research also includes pharmacogenomic investigations. This has led to speculation about the importance of drug-drug interactions involving antiemetics through competition for metabolism by the cytochrome P450 isoenzymes. The worst possible interaction would be a decrease in the effect of different cytotoxins but there is no evidence that such interactions are of importance in daily clinical practice. Guidelines are useful tools in the optimisation of antiemetic prophylaxis but, unfortunately, implementation of the evidence-based recommendations is far from successful. A prerequisite for further optimisation of antiemetic prophylaxis is updating of the guidelines, including recommendations for the use of NK 1 receptor antagonists (aprepitant), followed by implementation of these recommendations in the clinic. Future research must include 'the difficult trials' focusing on the remaining groups of patients with severe chemotherapy-induced nausea and vomiting, including patients with refractory and breakthrough emesis.
 ...
PMID:Risk-benefit of antiemetics in prevention and treatment of chemotherapy-induced nausea and vomiting. 1515 51