Metoclopramide effectiveness

The effects of metoclopramide are antagonized by concurrent administration of anticholinergics or narcotic analgesics. Metoclopramide may decrease the absorption of digoxin and cimetidine and increase absorption of acetaminophen, tetracyclines, and levodopa Metoclopramide may alter die body s insulin requirements. 

A PPI may be warranted in patients older than 60 years of age.29 Proton pump inhibitors are the most useful option because they have superior efficacy and are dosed once daily. Elderly patients maybe sensitive to the central nervous system effects of metoclopramide and H2RAs. 

Most common Sedation, restlessness, diarrhea (metoclopramide), agitation, central nervous system depression Less common Extrapyramidal effects (more frequent with higher doses), hypotension, neuroleptic syndrome, supraventricular tachycardia (with intravenous administration)... 

Metoclopramide crosses the BBB and has centrally-mediated adverse effects. Young children and the elderly are especially susceptible to these effects, which include somnolence, reduced mental acuity, anxiety, depression, and EPS (akathisia, dystonia, and tardive dyskinesia).30 The overall incidence of adverse effects is estimated to be 10% to 20%.1... 

Domperidone minimally crosses the BBB it acts in the CTZ which lies outside of the BBB. As such, domperidone is less likely to cause the centrally-mediated adverse effects seen with metoclopramide and has an estimated overall incidence of 5% to 10%.1,30 However, domperidone has been associated with prolonged QT intervals, cardiac arrhythmias, and sudden death.31 It should not be used for patients with underlying long QT interval or for those on other medications that prolong the QT interval. Both metoclopramide and domperidone can cause hyperprolactinemia, galactorrhea, and gynecomastia. 

Metoclopramide is the drug of choice for enhancement of lactation when improved feeding technique fails to increase milk flow48 (Table 44-5). Metoclopramide exerts its effect through dopamine antagonism. Increases in milk production should be noted within 2 to 5 days of metoclopramide initiation. Monitor patients for extrapyrimidal symptoms. 

Fever, rigors, chills, malaise headaches, myalgia Nausea, emesis Neutropenia Hepatic enzyme elevation Cutaneous—alopecia, transient, mild rashlike reaction Acetaminophen (APAP). NSAID if APAP is not effective. Meperidine for severe chills and rigors. Bedtime administration. 5-HT3 antagonist, prochlorperazine, metoclopramide, fluids Weekly complete blood count reduce dose by 30-50% Liver function tests (LFTs) weekly withhold treatment until LFTs normalize restart at 30-50% dose reduction reversible on dose reduction or cessation. Interferon is contraindicated in patients with psoriasis because exacerbation of psoriasis has been noted during IFN therapy. 

Malagelada JR, Rees WD, Mazzotta LJ, Go VL Gastric motor abnormalities in diabetic and postvagotomy gastroparesis Effect of metoclopramide and bethanechol. Gastroenterology 1980 78 286-293. 

The answer is c. (Hardman, pp 932—933.) Metoclopramide antagonizes the emetic effect of apomorphine, which is mediated by a dopamine... 

Effects similar to those of the neuroleptics have also been described for other dopamine-blocking agents. Thus, parkinsonism and tardive symptoms may result from use of metoclopramide, a drug which is commonly used to enhance gastric motility, or certain antiemetics, such as perphenazine. 

Baits containing this antiemetic at an effective concentration of 1 mg/kg BW shortened the median time for death for dogs from 151 min postdose for 1080 baits without metoclopramide to 132 min (Rathore 1985). At tested doses (1 to 16 mg/kg B W), metoclopramide did not decrease the frequency of vomiting by dogs, but did decrease the amount of vomitus (O Brien et al. 1986). 

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. 

Most of the antiemetic clinical trials in the last decade have involved metoclopramide (1) either as a single agent or in combination with other drugs. Similarly, most of the chemical modification studies have been designed to optimize antiemetic and/or gastroprokinetic properties of metoclopramide and to eliminate undesirable CNS side-effects which are the consequence of its dopamine D2 receptor blockade [1-3]. 

Another approach combined modification of the 2-substituent yielding dihy-drobenzofuran and pyrrolidinemethyl side-chain with unsubstituted (secondary) nitrogen to give ADR 851 (24) and ADR 847 (25) [18]. Both were reported to be somewhat more effective than metoclopramide as antagonists of cisplatin-induced emesis in the dog. In addition, ADR 847 enhanced gastric emptying [19]. 

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... 

A combined administration of metoclopramide and anticholinergic agent to reduce dystonic reactions of metoclopramide, did not diminish antiemetic efficacy in dogs [117], Thus, the inhibitory effect on GI smooth muscle by cholinergic blockade had no significant impact on antiemetic activity of metoclopramide. 

These compounds belong to a broad class of pharmacological agents possessing D2-dopamine blocking properties which are responsible for dystonic reactions. Prochlorperazine, the most widely used phenothiazine, was more effective than placebo but did not offer advantage over the cannabinoids or butyrophenones [123], It was less effective than metoclopramide against cisplatin [81]. 

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]. 

Recently, several 5-HT3 antagonists have been identified and found to be effective as antiemetics in animals (Table 7.2). These compounds as a class have been proven to be free of D2-dopamine blocking properties which are responsible for dystonic side-effects seen with metoclopramide. 

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-... 

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