Nausea/vomiting dopamine-induced

Dopamine is an intermediate product in the biosynthesis of noradrenaline. Furthermore it is an active transmitter by itself in basal ganglia (caudate nucleus), the nucleus accumbens, the olfactory tubercle, the central nucleus of the amygdala, the median eminence and some areas in the frontal cortex. It is functionally important, for example in the extra-pyramidal system and the central regulation of emesis. In the periphery specific dopamine receptors (Di-receptors) can be found in the upper gastrointestinal tract, in which a reduction of motility is mediated, and on vascular smooth muscle cells of splanchnic and renal arteries. Beside its effect on specific D-receptors, dopamine activates, at higher concentrations, a- and -adrenoceptors as well. Since its clinical profile is different from adrenaline and noradrenaline there are particular indications for dopamine, like situations of circulatory shock with a reduced kidney perfusion. Dopamine can dose-dependently induce nausea, vomiting, tachyarrhythmia and peripheral vasoconstriction. Dopamine can worsen cardiac ischaemia. 

The severe nausea and vomiting induced by cytotoxic drugs and radiation in man can be reduced by metoclopramide given either atone or in combination with other drugs, such as dexamethasone. However, the extrapyramidal side-effects induced by metoclopramide, due to antagonism of dopamine re-... 

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. 

HT3 antagonists are effective for acute nausea, but are not effective for anticipatory nausea, and efficacy is low for delayed nausea. Lorazepam is very effective for anticipatory nausea. Other agents used in chemotherapy-induced emesis are dopamine antagonists, scopolamine, and dronabinol. Antihistamines are generally less effective for chemotherapy-induced nausea and vomiting. 

Benserazide (BZ), 2-amino-3-hydroxy-A, -[(2,3,4-trihydroxyphenyl) methyl] propane hydrazide is an irreversible inhibitor of peripheral L-aromatic amino acid decarboxylase (AADC). The decarboxylase inhibitor drugs, e.g., carbidopa and benserazide, inhibit dopamine production outside the brain and permit direct deliveiy of dopamine (LD metabolite) to the brain. This synergistic therapy also minimizes the side effects such as nausea and vomiting induced by levodopa.1 2 Benserazide at the recommended therapeutic dose does not cross the blood-brain barrier to any significant degree. Synergistic effect of levodopa and benserazide reduces the required dose of levodopa for the optimal and earlier therapeutic response.3... 

Promethazine (e.g., Phenergan) Both a D2 dopamine antagonist and an H] histamine antagonist which is used to control motion sickness as well as nausea and vomiting. Particularly useful following surgery because it reduces anesthesia-related nausea, induces light sleep and reduces apprehension. 

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