Metoclopramide Alcohol

In general, ketones, alcohols and ethers of formula (3) showed comparable protection against cisplatin-induced emesis in the dog and ferret with that of metoclopramide. Erythro (cis) alcohols (3c, 3g, 3i) were found to be more potent than the corresponding threo-(trans) isomers (3d, 3h, 3j). Optical isomer (.R) (3e) was found to be somewhat more potent than its (S )-enantiomer (3f) as an antagonist of cisplatin-induced emesis in the ferret. In the dog, both isomers showed similar activity. A number of heterocyclic analogues were also studied but with the exception of (3k), all were inferior in potency as antiemetic agents compared with other compounds (3) shown in Table 7.1. Lead compound, BMY 25801, batanopride, (3a) is presently under clinical investigation. 

Drugs that may affect metoclopramide include levodopa, anticholinergics, and narcotic analgesics. Drugs that may be affected by metoclopramide include alcohol, cimetidine, cyclosporine, digoxin, levodopa, MAO inhibitors, and succinylcholine. 

Drugs and chemicals are known to cause activated interaction. The depressant action of opioid drugs is enhanced by drugs acting on the central nervous system (CNS) such as alcohol, anesthetics, anxiolytics, hypnotics, tricyclic antidepressants, and antipsychotics. Concomitant administration of opioid analgesics and monoamine oxidase inhibitors (MAOIs) should be avoided, or extra care should be taken if such a therapy is inevitable. Fatal reactions are reported when treated along with selegiline. Interactions also are reported with cyclizine, cimetidine, mexiletine, cisapride, metoclopramide, or domperidone. 

Alcohol Metoclopramide increases the rate of absorption and blood levels of alcohol and increases alcohol-related sedation. 

If there is impaired liver function, metoclopramide can accumulate. In eight patients with severe alcoholic cirrhosis there was a 50% lower clearance than in eight healthy volunteers the apparent volume of distribution and absolute systemic availability were similar in the two groups (15). 

Intravenous metoclopramide 20 mg accelerated gastric emptying and increased the rate of absorption of alcohol in seven subjects (18). In another similar study the sedative effects of alcohol were enhanced (19). 

Clinically important, potentially hazardous interactions with alcohol, amiodarone, anticholinergics, antihistamines, barbituates, cisapride, dofetilide, doxazosin, erythromycin, guanethidine, hydralazine, levodopa, lithium, methyldopa, metoclopramide, moxifloxacin, piperazine, quinidine, sibutramine, sotalol, thiazide diuretics, thioridazine... 

There is some evidence that metoclopramide can increase the rate of absorption of alcohol, raise maximum blood-alcohol levels, and possibly increase alcohol-related sedation. 

A study in 7 subjects found that 20 mg of intravenous metoclopramide increased the rate of alcohol absorption, and the peak blood levels were raised from 55 to 86 mg%. Similar results were seen in 2 healthy subjects given metoclopramide orally. Another study in 7 healthy subjects found that 10 mg of intravenous metoclopramide accelerated the rate of absorption of alcohol 70 mg/kg given orally, and increased its peak levels, but not to a statistically significant extent. Blood alcohol levels remained below 12 mg%. More importantly the sedative effects of the alcohol were increased. The reasons for this effect are not fully understood, but it appears to be related to an increase in gastric emptying. These two studies were done to find out more about intestinal absorption mechanisms rather than to identify daily practicalities, so the importance of the findings is uncertain. However, it seems possible that the effects of alcohol will be increased. Metoclopramide alone can sometimes cause drowsiness, and if affected, patients should not drive or operate machinery. 

Persky and Goldfrank (43 ) reviewed 86 methadone overdose cases in 81 patients all treated successfully with intravenous naloxone hydrochloride. Four patients had pulmonary oedema. In more than half, liver and muscle function studies showed abnormalities. 79 of the overdoses were associated with a combination of methadone and other non-opiate drugs, including alcohol. Cameron (9") described grossly depressed respiration after morphine, metoclopramide and naloxone were given in sequence. 

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