Antiemetics dopamine antagonists

Metoclopramide (Region, Clopro, Octamide) [Antiemetic/ Dopamine Antagonist] Uses Tx NA Action T UGI motility, blocks dopamine in chemoreceptor trigger zone Dose Adults. 10 mg IV, 10-20 mg IM Peds. 1-2 mg/kg IV/IM Caution [B, -] Drugs w/ extrapyramidal ADRs Contra ... 

Metoclopramide, administered at doses higher than those required to inhibit apomorphine-induced emesis, was more effective than haloperidol in antagonizing cisplatin-induced emesis in dogs [80]. This was observed despite the fact that metoclopramide was considerably weaker than haloperidol as a D2-dopamine antagonist [43]. Subsequently, antiemetic efficacy of metoclopramide administered at high doses has been reported in cancer patients... 

It had been reported that 5-HT and 2-Me-5-HT released DA in striatal slices [112]. The functional importance of this response is unknown, because the D2-dopamine antagonists are not efficient antiemetics against radiation- or chemotherapy-induced emesis. 

Substituted benzamides include metodopramide (discussed previously) and trimethobenzamide. Their primary mechanism of antiemetic action is believed to be dopamine-receptor blockade. Trimethobenzamide also has weak antihistaminic activity. For prevention and treatment of nausea and vomiting, metodopramide may be given in the relatively high dosage of 10-20 mg orally or intravenously every 6 hours. The usual dose of trimethobenzamide is 250 mg orally, 200 mg rectally, or 200 mg by intramuscular injection. The principal adverse effects of these central dopamine antagonists are extrapyramidal restlessness, dystonias, and parkinsonian symptoms. 

Prophylactic administration of antiemetics is essential in any patient receiving FOLFOX chemotherapy. The combination of oxaliplatin and 5-fluorouracil results in a moderate level of emetogenicity and requires the administration of 5HT3-receptor antagonists and corticosteroid treatment, generally with a dopamine antagonist such as metoclopramide or domperidone. Severe manifestations may have to be managed by delay and/or dose modification of the patient s next cycle of chemotherapy. 

NERVOUS SYSTEM DRUGS ANTIEMETICS Dopamine receptor antagonists... 

E Lorazepam is most effective for anticipatory nausea and vomiting, or emesis that oaurs prior to chemotherapy administration. The antiemetic effects may be related to the sedative and anxiolytic properties of lorazepam. 5-HT3 antagonists and dopamine antagonists are poor choices because efficacy has not been shown in anticipatory nausea and vomiting. 

Psychosis is caused by a dopamine (neurotransmitter) imbalance in the brain. Antipsychotic medications (dopamine antagonists) block the D2 dopamine receptors, reducing the psychotic symptoms. Some antipsychotic medications block the chemoreceptor trigger zone and vomiting (emetic) center, producing an antiemetic effect. Blocking dopamine causes the side effects of Parkinsonism (see 15.24 Parkinsonism Medication). Psychosis is treated with antipsychotic medications. Categories of antipsychotic are ... 

Antiemetics Antipsychotic agent Dopamine antagonist Anti-dyskinesia agent... 

Note that prochlorperazine should not be given if apomorphine is used for Parkinson s disease, as its dopamine antagonist actions can worsen the disease (see also Levodopa + Antiemetics , p.682). Because apomorphine is highly emetogenic at the doses required for the treatment of Parkinson s disease (1 to 4 mg/hour by subcutaneous infusion), patients with Parkinson s disease requiring apomorphine should be pretreated with domperidone 20 mg three times daily for at least 2 days. Rare reports of extrapyramidal adverse effects have been reported with ondansetron, which may be of relevance in patients with Parkinson s Disease. 

Alizapride is a dopamine antagonist with less affection on the CNS (central nervous system). It has a prokinetic and an antiemetic effect that can be used in the treatment of nausea and vomiting, including a postoperative side effect. 

Dronabinol (tetrahydrocannabinol), the active principle from cannabis and synthetic cannabinoids, nabilone and levonantradol are effective in treating nausea and vomiting in cancer chemotherapy. The mode of action is unclear but appears to involve cannabinoid CBi receptors. Cannabinoids have been shown to reduce acetylcholine release in the cortex and hippocampus, and have been suggested to inhibit medullary activity by a cortical action. Inhibition of prostaglandin synthesis and release of endorphins may also be involved in the antiemetic effect. A review of trials of dronabinol, nabilone or levonantradol concluded that while the cannabinoids were superior to placebo or dopamine receptor antagonists in controlling emesis... 

Apomorphine is approved for acute off episodes in patients with advanced stages of PD. The onset of effect is within 10 to 20 minutes and the duration of effect is about 60 minutes. It requires premedication with an antiemetic because it causes nausea and vomiting. Antiemetics that block central dopamine worsen the symptoms of PD, and 5-HT3 antagonists, such as ondansetron, can aggravate PD-related hypotension. Trimethobenzamide (300 mg three times daily) should be... 

Domperidone [133], one of the most potent D2-dopamine blockers and antagonists of apomorphine-induced emesis with limited brain-blood barrier permeability, did not establish a position as an antiemetic, especially against cisplatin [134], Recently, the use of domperidone as a parenteral antiemetic has been discontinued because of serious cardiovascular toxicity. 

Metoclopramide may be considered as a prototype 5-HT3 antagonist because its antiemetic efficacy both in animals and man could not be adequately explained by D2-dopamine blockade. In fact, metoclopramide was considerably weaker as a D2-antagonist than haloperidol or domperidone and yet it was effective against emesis induced by anticancer agents both in animals [43, 80] and cancer patients [135]. 

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