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NOVEMBER 2013 G GASTROPARESIS astroparesis is a condition characterised by delayed gastric emptying. It is often seen in people with longstanding diabetes mellitus (diabetic gastroparesis), commonly with other evidence of autonomic neuropathy. Coexisting anxiety and depression increase the prevalence of gastrointestinal symptoms in people with diabetes. Other conditions associated with gastroparesis include hypothyroidism, chronic kidney disease, reflux oesophagitis, Parkinson’s disease, stroke, multiple sclerosis, scleroderma, dermatomyositis, polymyositis, myotonic dystrophy, Crohn’s disease and functional bowel disorders. Some people report a sudden onset of symptoms of gastroparesis after an acute viral illness. Gastroparesis may also occur after surgery. Signs and symptoms Symptoms of gastroparesis include: ■■ Nausea ■■ Vomiting ■■ Early satiety ■■ Postprandial fullness ■■ Loss of appetite ■■ Bloating ■■ Upper abdominal pain Around 10% of people with diabetes will have symptoms of gastroparesis. This is largely due to diabetic neuropathy in the stomach. They may also show postprandial hypoglycaemia or deterioration in diabetic control. Uncontrolled blood glucose levels may aggravate symptoms of gastroparesis and delay gastric emptying. Pain occurs in about 20% of patients with gastroparesis and impairs quality of life. Medication-related causes A number of medications can delay gastric emptying including opioids (morphine, oxycodone, tramadol), anticholinergic agents, calcium channel blockers, clonidine (Catapres) and glucagon like peptide-1 (GLP-1) agents used in diabetes. GLP-1 analogues or incretins include exenatide (Byetta) and liraglutide (Victoza). This class of medications for the © Manrex Pty Ltd (ABN: 63 074 388 088) t/as Webstercare - 2013 treatment of type 2 diabetes increases glucose-dependent insulin secretion, and suppresses inappropriate glucagon secretion. The delay gastric emptying slows glucose absorption, and decreases appetite. Another new class of medications for type 2 diabetes, DPP-4 inhibitors or gliptins, do not delay gastric emptying. This includes linagliptin (Trajenta), saxagliptin (Onglyza), sitagliptin (Januvia) and vildagliptin (Galvus). Management Management of gastroparesis should include assessment and correction of nutritional state, relief of symptoms, improvement of gastric emptying and, in diabetes, control of blood glucose levels. Nutrition and hydration Frequent small volume nutrient meals that are low in fat and soluble fibre are recommended. Hard-to-digest foods like apples with their skin on, or high-fibre foods like oranges and broccoli should be avoided. Liquids may be easier to digest. For residents unable to tolerate solid food, the next step is to trial homogenised or liquid nutrient meals. For those with severe disease unable to tolerate oral intake, enteral alimentation (nasojejunal feeding) and parenteral nutrition are options. Medications Drug treatment of gastroparesis includes the use of prokinetic and antiemetic medications. Prokinetic agents include ■■ domperidone (Motilium) 10 to 20 mg orally, 3 to 4 times daily before meals ■■ metoclopramide (Maxolon) 5 to 10 mg orally, 3 to 4 times daily before meals ■■ erythromycin 250mg orally, 3 to 4 times a day 30 minutes before meals Prokinetic drugs can potentially improve glycaemic control in diabetic gastroparesis by allowing a more predictable absorption of nutrients. Combinations of prokinetic drugs could be more effective than a single agent. GASTROPARESIS Domperidone Domperidone is considered first-line therapy for the treatment of gastroparesis. It has equal efficacy to metoclopramide, but with lower side effects. The main benefit is seen with a reduction in nausea and vomiting. Domperidone does not cause central side effects such as confusion, sedation and movement disorders, as it does not cross the blood brain barrier. A TGA alert in December 2012 highlighted concerns about an increased risk of serious ventricular arrhythmias or sudden cardiac death with domperidone. This is especially evident in people older than 60 years of age and with higher doses (daily doses greater than 30mg daily). Signs and symptoms of abnormal heart rate or rhythm include dizziness, palpitations, syncope and seizures. Domperidone should not be administered with ketoconazole, erythromycin or other potent CYP3A4 inhibitors which prolong QTc interval such as fluconazole, voriconazole, clarithromycin and amiodarone. Itraconazole and verapamil can also significantly increase the blood levels of domperidone. Domperidone is the preferred prokinetic agent in people with Parkinson’s disease. Metoclopramide Erythromycin also has many drug-drug interactions and can cause QT prolongation, increasing the risk of arrhythmias. Others Other medications used off-label include most antiemetic drugs (e.g. prochlorperazine) and antihistamines (e.g. promethazine). Ondansetron (Zofran) is no more effective than metoclopramide and promethazine (Phenergan). Tricyclic antidepressants (TCAs) in low doses can be considered for nausea and vomiting in gastroparesis not controlled by first-line therapies. TCAs with strong anticholinergic properties such as amitriptyline (Endep) should be avoided, and nortriptyline (Allegron) is the preferred choice. A single report has shown that mirtazapine (Avanza, Remeron, Milivin) is effective. Pain relief is sometimes required. Preferred agents are lowdose tricyclic antidepressants, duloxetine (Cymbalta) and pregabalin (Lyrica). NSAIDs should be avoided because of the potential to worsen kidney function in people with diabetes. Tramadol and opioids should also be avoided as they reduce gastric motility. Other treatments Gastric electrical stimulation may control symptoms of gastroparesis. Some benefit may be obtained with acupuncture and pyloric botulinum toxin injection. Metoclopramide is also considered first-line therapy for the treatment of gastroparesis, although for no longer than 12 weeks. Tardive dyskinesia affects mainly older women after one and a half to two years of therapy. Most common side effects include acute dystonias, so metoclopramide should be stopped if involuntary movements occur. As prolonged reactions are more common in older people, the dose should be commenced at 5mg three times daily before meals. Summary Many drug-drug metoclopramide. References Am J Gastroenterol 2013;108:18-37. Curr Opin Gastroenterol 2012;28(6):621-8. Australian Prescriber 2012;3(6):199. Therapeutic Guidelines 2013. interactions can occur with Erythromycin The antibiotic erythromycin also has prokinetic properties when administered IV or orally. IV injection is usually reserved by acute conditions. Erythromycin stimulates gastrointestinal contractions and results in increased GI motility. Tachyphylaxis develops rapidly during chronic oral use. The clinical response drops after 4 weeks of oral therapy, however some may continue to experience benefit. It may make upper gastrointestinal symptoms worse, especially at higher doses. An added benefit to erythromycin is its availability in a liquid form, which may be more effective than a tablet. © Manrex Pty Ltd (ABN: 63 074 388 088) t/as Webstercare - 2013 Gastroparesis may cause severe symptoms and result in nutritional deficiencies, impaired glucose control and poor quality of life. Management is usually tailored to the severity of the condition. Mild gastroparesis may be controlled with lifestyle and dietary modifications. The choice of prokinetic agents in more troublesome forms of the condition is often guided by the potential for drug interactions and the predominant symptom.