Prochlorperazine antiemetic effects

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). 

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. 

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. 

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. 

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]. 

The antiemetic effect of nabilone in the clinic is well established in numerous studies. In an early study with 113 patients undergoing cancer chemotherapy with a wide variety of anticancer drugs, 80% experienced full or partial improvement of nausea and emesis while only 36% responded to prochlorperazine treatment. Drowsiness and dizziness were reported in many cases. Euphoria (16%), dry mouth and blurred vision (4.5 %), orthostatic hypotension (1 %) and visual hallucinations (1 %) were the more serious side-effects [ 167]. This general picture has been repeated over and over again. 

Prochlorperazine is thought to exert its antipsychotic effects by postsynaptic blockade of CNS dopamine receptors, thus inhibiting dopamine-mediated effects. Its antiemetic effects are attributed to dopamine receptor blockade in the medullary chemoreceptor trigger zone (Figure 73). 

FIGURE 81 Phenothiazine derivatives such as chlorpromazine, perphenazine, prochlorperazine, promethazine, triethylperazine, and triflupro-mazine, exert their antiemetic effects by blocking the dopamine receptors in the area postrema. 

Nonpsychiatric indications With the exception of thioridazine, most phenothiazines have antiemetic actions prochlorperazine is promoted solely for this indication. Hj receptor blockade, mosi often present in short side-chain phenothiazines, provides the basis for their use as antipruritics and sedatives and contributes to their antiemetic effects. 

Meanwhile, antagonism of dopamine D2-type receptors in the chemoreceptor trigger zone in the brainstem is responsible for beneficial antiemetic effects produced by neuroleptics. Several phenothiazines (e.g., promethazine and prochlorperazine) are marketed to exploit this pharmacological effect. 

The piperzine group produces a low sedative effect and a strong antiemetic effect, more EPS, and little effect on blood pressure. Included in this group are prochlorperazine (Compazine), fluphenazine (Prolixin), perphenazine (Trilafon), and trifluoperazine (Stelazine). 

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. 

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. 

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. 

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). 

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. 

Phenothiazines such as prochlorperazine, thiethylperazine, and chlorpromazine see Chapter 18) are among the most commonly used antinauseants and antiemetics. Their principal mechanism of action is dopamine receptor antagonism at the CTZ. Compared to metoclopramide or ondansetron see above), these drugs do not appear to be as uniformly effective in cancer chemotherapy-induced emesis. On the other hand, they also possess antihistaminic and anticholinergic activities, which are of value in other forms of nausea, such as motion sickness. 

The 8-year-old child diagnosed with gastroenteritis is admitted to the pediatric unit. The nurse administered prochlorperazine (Compazine), an antiemetic, rectally. Which side effects should the nurse assess for ... 

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