Prokinetics

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PROKINETICS

Prokinetics

PROKINETICS – INTRODUCTION

Prokinetic agents, or prokinetics, are medications that help control acid reflux. Prokinetics help strengthen the lower esophageal sphincter (LES) and cause the contents of the stomach to empty faster. This allows less time for acid reflux to occur.

Prokinetic drugs increase the movement of ingested material through the GI tract.

They are useful in the treatment of motility disorders, because they induce coordinated motility patterns.

One of the class of drugs used on the digestive system, including all drugs whose primary effect is to augment the speed of intestinal transit, by increasing the frequency of contractions in the small intestine or making them stronger, but without disrupting their rhythm.

 

PROKINETICS – INDICATION

They are used to relieve gastrointestinal symptoms such as abdominal discomfort, bloating, constipation, heart burn, nausea, and vomiting. They are used to treat a number of gastrointestinal disorders, including irritable bowel syndrome, gastritis, acid reflux disease, gastroparesis, and functional dyspepsia.

Prokinetics are typically used with other gastroesophageal reflux disease (GERD) or heartburn  medications, such as proton pump inhibitors (PPIs) or H2 receptor blockers. Unlike these other acid reflux medications, which all generally are safe, prokinetics may have serious or even dangerous side effects. They’re often only used in the most serious cases of GERD.

For example, prokinetics might be used to treat patients who also have insulin-dependent diabetes, or infants and children with significantly impaired bowel emptying or severe constipation that doesn’t respond to other treatments.

 

PROKINETICS – INFORMATION

Most patients with gastroparesis require drug therapy, and for most this needs to continue long term. Drugs that increase the rate of gastric emptying — prokinetics — are generally prescribed in order to relieve symptoms, although as discussed, the presence of symptoms often correlates poorly with the rate of gastric emptying. Most of the available prokinetic drugs have multiple actions, targeting both sensory and motor pathways, and the agents providing greatest symptom relief are not necessarily the most potent in terms of their capacity to accelerate emptying. Patients with upper-gastrointestinal symptoms but normal gastric emptying might therefore respond to prokinetic therapy, and furthermore, these medications are likely to have a placebo effect in a proportion of patients. The prokinetics metoclopramide, domperidone, and cisapride are all reported to improve disturbances of the gastric electrical rhythm, and might provide greater symptomatic relief than the more potent prokinetic erythromycin, which can increase gastric dysrhythmias.

Rather than simply stimulating an increased frequency or amplitude of gastric contractions, such as with bethanechol or acetylcholinesterase inhibitors, effective prokinetic drugs, such as cisapride, stimulate coordinated sequences of pressure waves in the antrum, pylorus and duodenum. Some prokinetic agents, including cisapride, also relax the fundus, which might improve symptoms in a subgroup of patients, independent of their effects on gastric emptying; conversely, erythromycin increases fundic tone.

In addition to treating symptoms, prokinetic drugs could potentially improve glycemic control in diabetic gastroparesis by allowing a more predictable absorption of nutrients, matched to the action of exogenous insulin, but evidence to support this strategy is limited. In type 2 diabetes, which is characterized by diminished and delayed endogenous insulin release, slower gastric emptying might actually improve glycemic control because nutrients are absorbed more slowly, so there might be no reason to use prokinetic drugs in the absence of symptoms.

The choice of prokinetic drug is determined by local availability, the side-effect profile, and the clinician’s personal experience with the drug, and there are few data comparing the drugs directly. Combinations of prokinetic drugs could be more effective than a single agent, but this issue has not been sufficiently evaluated. Most reports of drug efficacy relate to short-term usage, and there is some concern that longer term use of metoclopramide, domperidone, and erythromycin might result in tachyphylaxis.

PROKINETIC DRUGS:

  • Metoclopramide

Dogs and cats: 0.2–0.5 mg/kg, PO or SC, tid; 0.01–0.02 mg/kg/hr, IV infusion

Horses: 0.125–0.25 mg/kg, diluted in 500 mL of polyionic solution and administered IV over 60 min

  • Domperidone

0.1–0.5 mg/kg, IM; 0.5–1 mg/kg, PO

  • Cisapride

Dogs: 0.1 mg/kg, PO, tid

Cats: 2.5 mg/cat, tid for cats <5 kg, and 5 mg/cat for cats >5 kg

  • Ranitidine

1–2 mg/kg, PO, bid

  • Nitazidine

2.5–5 mg/kg, PO, bid

  • Lidocaine

Horses: 1.3 mg/kg, IV, as a bolus followed by a continuous infusion of 0.05 mg/kg/min

PROKINETICS

 

By Medifit Education

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