Apomorphine Antiemetics

Apomorphine (Apokyn ) Activate postsynaptic D1 and D2 DA receptors Start an antiemetic for 3 days, then give apomorphine 2 mg SC injection (1 mg if outpatient) while monitoring blood pressure then increase by 1 to 2 mg every 2 or more hours usual MD is 2-6 mg 3-5 times daily for off periods... 

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... 

Apomorphine is a nonergot dopamine agonist given as a subcutaneous rescue injection. For patients with advanced PD with intermittent off episodes despite optimized therapy, subcutaneous apomorphine triggers an on response within 20 minutes, and duration of effect is up to 100 minutes. Most patients require 0.06 mg/kg. Prior to injection, patients should be premedicated with the antiemetic trimethobenzamide. It is contraindicated with the serotonin-3-receptor blockers (e.g., ondansetron). 

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... 

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. 

Concomitant medication - Do not initiate apomorphine without the use of a concomitant antiemetic. Start trimethobenzamide (300 mg 3 times daily orally) 3 days prior to the initial dose of apomorphine and continue during at least the first 2 months of therapy. 

Nausea and Vomiting At the recommended doses of apomorphine, severe nausea and vomiting can be expected. There was no experience with antiemetics other than trimethobenzamide. Some antiemetics with anti-dopaminergic actions have the potential to worsen the clinical state of patients with PD and should be avoided. 

B. Two medicines, ipecac and apomorphine, induce vomiting. Metoclopramide is a prokinetic with antiemetic properties and therefore would have the opposite of the desired effect. Morphine is an opioid with analgesic and sedating properties. Promethazine and ondansetron are also antiemetics, not emetics. 

Nausea is often troublesome, especially at the initiation of apomorphine treatment accordingly, pretreatment with the antiemetic trimethobenzamide (300 mg three times daily) for 3 days is recommended before apomorphine is introduced and is then continued for at least 1 month, if not indefinitely. Other adverse effects include dyskinesias, drowsiness, chest pain, sweating, hypotension, and bruising at the injection site. Apomorphine should be prescribed only by physicians familiar with its potential complications and interactions. 

Antiemetics. Diphenidol (l,l-diphenyl- 4—piperidlnobutanol) has been reported to have antiemetic activity equal to chlorpromazine, but without many of the central neirvous system actions of the phenothia-zines. It blocked apomorphine induced emesis by oral, i.m., and rectal administration. In clinical trials dephenidol was found to be more effective than a placebo for relief of nausea and vomiting, with few side effectsxt was also found to be effective against various types of vomiting in man in an uncontrolled experiment. 

Very few other cannabinoids have been tested (or at least reported) in animals. A-Methyllevonantradol (cf. 9) and nabilone (39) have been compared in the cat model [151]. Both cannabinoids showed dose-dependent antiemetic activity at the 20-100 mg/kg dose levels, A-methyllevonantradol being ca. 5-times more active than nabilone. The latter drug had previously been shown to suppress in the cat emesis induced by apomorphine, deslanoside and the anticancer drugs l,3-bis(2-chlorethyl)-l-nitrosourea (BCNU) and cisplatin, but not nicotine. At the doses tested (25-100/ig/kg), nabilone produced behavioural disturbances, from mild ataxia and display of pleasure at 25 /ig/kg to severe locomotor disturbance, catatonic behaviour and vocalization at 100 /ig/kg. 

Apomorphine is a potent dopamine receptor agonist used in advanced disease. It has to be administered by subcutaneous injection and causes such severe nausea and vomiting that an antiemetic (domperidone) has to be administered for two days prior to treatment. 

The antiemetic properties of metoclopramide appear to be a result of its antagonism of central and peripheral dopamine receptors. Dopamine produces nausea and vomiting by stimulation of the medullary chemoreceptor trigger zone (CTZ), and metoclopramide blocks stimulation of the CTZ by agents like levodopa or apomorphine that are known to increase dopamine levels or to possess dopaminelike effects. Metoclopramide also inhibits the central and peripheral effects of apomorphine and abolishes the slowing of gastric emptying caused by apomorphine. 

The hypotensive adverse effects of apomorphine may possibly be increased by alcohol. The concurrent use of other drugs used for erectile dysfunction or dopamine agonists or antagonists is not recommended. However, domperidone, and prochlorperazine are said not to interact when apomorphine is used for erectile dysfunction, and domperidone is the recommended antiemetic when apomorphine is used for Parkinson s disease. There is evidence that antidepressants, antiepileptics, and ondansetron do not interact adversely. 

The small doses of apomorphine used for erectile dysfunction (2 to 3 mg) do not normally cause vomiting, but nausea does occur in about 7% of patients and the manufacturers say that interaction studies and/or clinical experience show that domperidone, ondansetron or prochlorperazine may safely be given as antiemetics in this patient group. Studies with other antiemetics have not been carried out, so at the moment concurrent use is not recommended. ... 

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. 

The antiemetic activity of A -THC was initially investigated in the dog following clinical observations that it may possess antiemetic potential against chemotherapy-induced emesis. However, both A -THC and its analog nabilone failed to prevent vomiting in dogs produced by cisplatin (81) or apomorphine (82,83). On the other hand, both agents were effectively shown to prevent cis-... 

Antiemetic CPZ (100) PCP( = 35)>TFP (6) >TPP (0.5) The comparative dose required to abolish emesis induced by a fixed quantity of apomorphine. Inversely proportional to donor strength. 

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