Antiemetics prochlorperazine

Thirty randomized, controlled trials from 1975 to 1996 were analyzed to quantify the antiemetic efficacy and adverse effects of cannabis when given to 1366 patients receiving chemotherapy. Oral nabUone, oral dronabinol, and intramuscular levonantradol were compared with conventional antiemetics (prochlorperazine, metoclopramide, chlor-promazine, thiethylperazine, haloperidol, domperidone, and aliza-pride) or placebo. Across all trials, cannabinoids were slightly more effective than active comparators and placebo when the chemotherapy regimen was of moderate emetogenic potential, and patients preferred them. No dose-response relationships were evident to the authors. The cannabinoids were also more toxic side effects included euphoria, drowsiness, sedation, somnolence, dysphoria, depression, hallucinations, and paranoia. The efficacy of cannabinoids as compared to SSRls has not been studied. Use of these agents should be considered when other regimens do not provide desired efficacy. 

When ondansetron is administered with rifampin, blood levels of ondansetron may be reduced, decreasing the antiemetic effect. Dimenhydrinate may mask the signs and symptoms of ototoxicity when administered with ototoxic drugp, such as the aminoglycosides (see Chap. 10), causing irreversible hearing damage. When lithium is administered with prochlorperazine, the risk of extrapyramidal reactions increases (see Chap. 32). 

Chlorpromazine, prochlorperazine, promethazine, methylprednisolone, lorazepam, metoclopramide, dexamethasone, or dronabinol may be used for adult patients. Around the clock dosing should be considered. The choice of specific agent should based on patient specific factors, including potential for adverse drug reactions, and cost. SSRIs are effective for breakthrough nausea and vomiting but they are not superior to the less expensive antiemetics above. 

THC is effective in several chemotherapy regimens, including methotrexate and the doxorubicin/cyclophosphamide/fluorouracil combination. Cisplatin treatment, however, is more resistant. Side effects of THC are generally well tolerated, and use may be limited in the elderly or with higher doses. Nabilone is a synthetic cannabinoid that is more effective than prochlorperazine in chemotherapy-induced emesis, including cisplatin. Its side effects are similar to THC. Levonantradol is another synthetic cannabinoid with antiemetic effects, and may be administered orally or intramuscularly. The side effect of dysphoria may limit its use. 

Antiemetics such as meclozine and prochlorperazine may alleviate light-headedness. In benign postural light-headedness the best treatment is mobilisation and some physical manoeuvres. Do not forget... 

The antiemetic site of action of tetrahydrocannabinol (THC) Marinot) is unknown, although it appears to affect the central cerebral cortex axis. Relief may occur in individuals refractory to other antiemetics. It is less effective in the elderly, primarily because of its side effects. The antiemetic effect is associated with a high, and this appears to be better tolerated in the young. Sedation is seen in approximately 30% of patients. Ataxia, drowsiness, dry mouth, or orthostatic hypotension may be seen in up to 35% of the older patient population. GI absorption is variable, though blood levels correlate with efficacy. The bioavailabiUty is not as variable if the agent is smoked. The coadministration of prochlorperazine may prevent some of the central nervous system side effects seen with the use of tetrahydrocannabinol. 

The answer is d. (Hardman, p 414.) Antipsychotic agents, particularly prochlorperazine, are also useful as antiemetic agents, thought to be due to dopamine blockade at the stomach and at the chemoreceptor trigger zone of the medulla. 

Most older typical antipsychotic drugs, with the exception of thioridazine, have a strong antiemetic effect. This action is due to dopamine-receptor blockade, both centrally (in the chemoreceptor trigger zone of the medulla) and peripherally (on receptors in the stomach). Some drugs, such as prochlorperazine and benzquinamide, are promoted solely as antiemetics. 

Phenothiazines are antipsychotic agents that can be used for their potent antiemetic and sedative properties (see Chapter 29). The antiemetic properties of phenothiazines are mediated through inhibition of dopamine and muscarinic receptors. Sedative properties are due to their antihistamine activity. The agents most commonly used as antiemetics are prochlorperazine, promethazine, and thiethylperazine. 

Prochlorperazine Maleate. 2-Chloro-10-[3-(4-methyl-l-piperazinyl)-propyl]-10 H-phenothiazine maleate [84-02-6] (Compazine) (22) is a white or pale yellow crystalline powder. It is almost completely odorless, its saturated solution is acidic to litmus, it is practically insoluble in water and ethanol, and it is slightly soluble in warm chloroform. It may be made by the synthesis described in Reference 18. Prochlorperazine maleate [84-02-6] is an effective antiemetic and tranquilizing agent. It is not particularly effective for motion sickness. Adverse reactions that may occur include extrapyramidal reactions, motor resdessness, dystonias, tardive dyskinesia, and contact dermatitis. Prochlorperazine is also a significant phenothiazine antipsychotic. 

Dronabinol (A9-tetrahydrocannabinol THC Marinol) is FDA approved for treatment of nausea and vomiting associated with cancer chemotherapy in patients who have failed to respond adequately to conventional antiemetics. With mildly or moderately emetogenic chemotherapy, it is more effective than placebo and equivalent or superior to oral prochlorperazine. Dry mouth, sedation, orthostatic hypotension, ataxia, dizziness, and dysphoria occur frequently, particularly in middle-aged and older patients. 

Various neuroleptics are also used for nonpsychiatric purposes, usually in smaller doses for shorter durations. However, severe effects can sometimes develop from these limited uses. Reserpine (Serpasil) is a neuroleptic that is more often used to suppress the symptoms of tardive dyskinesia (chapter 4). Prochlorperazine (Compazine) is used as an antiemetic and rarely as a neuroleptic. If given in sufficient doses to manifest psychoactive effects, these drugs produce the same emotional indifference as the other antipsychotic drugs. 

In our 1987 review, we summarized the research and clinical experience in this area [1], Surprisingly, in spite of the enormous public interest in medical marijuana and countless articles in the daily press and magazines focused predominantly on this aspect of marijuana use, little progress has been reported on the antiemetic activity of cannabinoids in the last decade. Plasse et al. have reviewed the clinical experience gained over 7 years with dronabinol (d9-THC) in antiemetic treatment [117]. With doses of 7 mg/m2 or below, complete response was noted in 36% of the patients, 32% showed partial response and 32% showed no response. However, 65% displayed drowsiness and dizziness and 12% had dysphoric effects. Combination treatment of dronabinol with prochlorperazine (a dopamine receptor blocker widely used as an antipsychotic drug with antiemetic effects) was more effective than each drug alone [118]. 

A 36-year-old woman with rapid-cycling bipolar II disorder and premenstrual mood exacerbation was treated as an out-patient with lamotrigine 400 mg/day, clonazepam 0.5 mg tds, and quetiapine 100 mg/day. She gained 9 kg in 6 months and was advised to reduce the dose of quetiapine to 50 mg/day. After 1 day, she reported nausea, dizziness, headache, and anxiety severe enough to preclude normal daily activities. She was instructed to take quetiapine 75 mg/day, but her symptoms continued and only resolved when she took 100 mg/day. Slower reduction in the dose of quetiapine (by 12.5 mg/day every 5 days) with an antiemetic, ondansetron, also failed. On a third attempt, prochlorperazine successfully reduced her withdrawal symptoms, although moderate nausea persisted for 2 days after complete withdrawal. 

All antiemetics are well absorbed from the gastrointestinal tract, with a C 3x of hours following an oral dose. Domperidone, granisetron, ondansetron, prochlorperazine and promethazine undergo extensive first-pass metabolism, which reduces bioavailability. 

All antiemetics are hepatically metabolised to a lesser or greater degree. Domperidone and prochlorperazine in particular have a very high first-pass effect and are extensively metabolised by the liver. 

Hepatic adverse effects secondary to antiemetic therapy are usually asymptomatic. Metoclopramide has been reported as causing cholestasis and the formation of arteriovenous shunts in the liver [12]. The 5HTj-receptor antagonists have all been documented as occasionally causing mild increases in liver fimction tests. Cholestatic jaundice has been reported with cyclizine, prochlorperazine and promethazine, and hepatitis has been reported with cyclizine. 

Initial nausea and vomiting are common an antiemetic, e.g. prochlorperazine, controls it and can generally be withdrawn after 4-5 days. 

Nabilone is a synthetic cannabinoid and has properties similar to tetrahydrocannabinol (the active constituent of marijuana) which has an antiemetic action. It is used to relieve nausea or vomiting caused by cytotoxic drugs. Adverse effects include somnolence, dry mouth, decreased appetite, dizziness, euphoria, dysphoria, postural hypotension, confusion and psychosis. These may be reduced if prochlorperazine is given concomitantly. 

Prophylactic administration of intramuscular prochlorperazine 12.5 mg did not prevent meptazinol-induced emesis in fact, the incidence of vomiting with this combination was twice the expected frequency cyclizine was an effective antiemetic (3). Prolonged vomiting has followed the use of intravenous meptazinol 50 mg (4). 

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